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1
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Colins Rodriguez A, Loft MSE, Schiessl I, Maravall M, Petersen RS. Sensory adaptation in the barrel cortex during active sensation in the behaving mouse. Sci Rep 2024; 14:21588. [PMID: 39284900 PMCID: PMC11405846 DOI: 10.1038/s41598-024-70524-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Accepted: 08/19/2024] [Indexed: 09/20/2024] Open
Abstract
Sensory Adaptation (SA) is a prominent aspect of how neurons respond to sensory signals, ubiquitous across species and modalities. However, SA depends on the activation state of the brain and the extent to which SA is expressed in awake, behaving animals during active sensation remains unclear. Here, we addressed this question by training head-fixed mice to detect an object using their whiskers and recording neuronal activity from barrel cortex whilst simultaneously imaging the whiskers in 3D. We found that neuronal responses decreased during the course of whisker-object touch sequences and that this was due to two factors. First, a motor effect, whereby, during a sequence of touches, later touches were mechanically weaker than early ones. Second, a sensory encoding effect, whereby neuronal tuning to touch became progressively less sensitive during the course of a touch sequence. The sensory encoding effect was whisker-specific. These results show that SA does occur during active whisker sensing and suggest that SA is fundamental to sensation during natural behaviour.
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Affiliation(s)
- Andrea Colins Rodriguez
- Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M13 9PT, UK
| | - Michaela S E Loft
- Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M13 9PT, UK
| | - Ingo Schiessl
- Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M13 9PT, UK
- Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust, University of Manchester, Manchester, M6 8HD, UK
| | - Miguel Maravall
- Sussex Neuroscience, School of Life Sciences, University of Sussex, Brighton, BN1 9RH, UK
| | - Rasmus S Petersen
- Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M13 9PT, UK.
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2
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Dobler Z, Suresh A, Chari T, Mula S, Tran A, Buonomano DV, Portera-Cailliau C. Adapting and facilitating responses in mouse somatosensory cortex are dynamic and shaped by experience. Curr Biol 2024; 34:3506-3521.e5. [PMID: 39059392 PMCID: PMC11324963 DOI: 10.1016/j.cub.2024.06.070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 05/10/2024] [Accepted: 06/26/2024] [Indexed: 07/28/2024]
Abstract
Sensory adaptation is the process whereby brain circuits adjust neuronal activity in response to redundant sensory stimuli. Although sensory adaptation has been extensively studied for individual neurons on timescales of tens of milliseconds to a few seconds, little is known about it over longer timescales or at the population level. We investigated population-level adaptation in the barrel field of the mouse somatosensory cortex (S1BF) using in vivo two-photon calcium imaging and Neuropixels recordings in awake mice. Among stimulus-responsive neurons, we found both adapting and facilitating neurons, which decreased or increased their firing, respectively, with repetitive whisker stimulation. The former outnumbered the latter by 2:1 in layers 2/3 and 4; hence, the overall population response of mouse S1BF was slightly adapting. We also discovered that population adaptation to one stimulus frequency (5 Hz) does not necessarily generalize to a different frequency (12.5 Hz). Moreover, responses of individual neurons to repeated rounds of stimulation over tens of minutes were strikingly heterogeneous and stochastic, such that their adapting or facilitating response profiles were not stable across time. Such representational drift was particularly striking when recording longitudinally across 8-9 days, as adaptation profiles of most whisker-responsive neurons changed drastically from one day to the next. Remarkably, repeated exposure to a familiar stimulus paradoxically shifted the population away from strong adaptation and toward facilitation. Thus, the adapting vs. facilitating response profile of S1BF neurons is not a fixed property of neurons but rather a highly dynamic feature that is shaped by sensory experience across days.
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Affiliation(s)
- Zoë Dobler
- Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095, USA; Neuroscience Interdepartmental Program, University of California, Los Angeles, 695 Charles Young Drive South, Los Angeles, CA 90095, USA
| | - Anand Suresh
- Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095, USA
| | - Trishala Chari
- Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095, USA; Neuroscience Interdepartmental Program, University of California, Los Angeles, 695 Charles Young Drive South, Los Angeles, CA 90095, USA
| | - Supriya Mula
- Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095, USA
| | - Anne Tran
- Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095, USA
| | - Dean V Buonomano
- Department of Neurobiology, David Geffen School of Medicine, 10833 Le Conte Ave, Los Angeles, CA 90095, USA; Department of Psychology, University of California, Los Angeles, 502 Portola Plaza, Los Angeles, CA 90095, USA
| | - Carlos Portera-Cailliau
- Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095, USA; Department of Neurobiology, David Geffen School of Medicine, 10833 Le Conte Ave, Los Angeles, CA 90095, USA.
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3
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Crombie D, Spacek MA, Leibold C, Busse L. Spiking activity in the visual thalamus is coupled to pupil dynamics across temporal scales. PLoS Biol 2024; 22:e3002614. [PMID: 38743775 PMCID: PMC11093384 DOI: 10.1371/journal.pbio.3002614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Accepted: 04/05/2024] [Indexed: 05/16/2024] Open
Abstract
The processing of sensory information, even at early stages, is influenced by the internal state of the animal. Internal states, such as arousal, are often characterized by relating neural activity to a single "level" of arousal, defined by a behavioral indicator such as pupil size. In this study, we expand the understanding of arousal-related modulations in sensory systems by uncovering multiple timescales of pupil dynamics and their relationship to neural activity. Specifically, we observed a robust coupling between spiking activity in the mouse dorsolateral geniculate nucleus (dLGN) of the thalamus and pupil dynamics across timescales spanning a few seconds to several minutes. Throughout all these timescales, 2 distinct spiking modes-individual tonic spikes and tightly clustered bursts of spikes-preferred opposite phases of pupil dynamics. This multi-scale coupling reveals modulations distinct from those captured by pupil size per se, locomotion, and eye movements. Furthermore, coupling persisted even during viewing of a naturalistic movie, where it contributed to differences in the encoding of visual information. We conclude that dLGN spiking activity is under the simultaneous influence of multiple arousal-related processes associated with pupil dynamics occurring over a broad range of timescales.
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Affiliation(s)
- Davide Crombie
- Division of Neuroscience, Faculty of Biology, LMU Munich, Munich, Germany
- Graduate School of Systemic Neurosciences, LMU Munich, Munich, Germany
| | - Martin A. Spacek
- Division of Neuroscience, Faculty of Biology, LMU Munich, Munich, Germany
| | - Christian Leibold
- Division of Neuroscience, Faculty of Biology, LMU Munich, Munich, Germany
- Fakultät für Biologie & Bernstein Center Freiburg, Albert-Ludwigs-Universität Freiburg, Freiburg im Breisgau, Germany
| | - Laura Busse
- Division of Neuroscience, Faculty of Biology, LMU Munich, Munich, Germany
- Bernstein Center for Computational Neuroscience, Munich, Germany
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4
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Velasco E, Zaforas M, Acosta MC, Gallar J, Aguilar J. Ocular surface information seen from the somatosensory thalamus and cortex. J Physiol 2024; 602:1405-1426. [PMID: 38457332 DOI: 10.1113/jp285008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 02/20/2024] [Indexed: 03/10/2024] Open
Abstract
Ocular Surface (OS) somatosensory innervation detects external stimuli producing perceptions, such as pain or dryness, the most relevant symptoms in many OS pathologies. Nevertheless, little is known about the central nervous system circuits involved in these perceptions, and how they integrate multimodal inputs in general. Here, we aim to describe the thalamic and cortical activity in response to OS stimulation of different modalities. Electrophysiological extracellular recordings in anaesthetized rats were used to record neural activity, while saline drops at different temperatures were applied to stimulate the OS. Neurons were recorded in the ophthalmic branch of the trigeminal ganglion (TG, 49 units), the thalamic VPM-POm nuclei representing the face (Th, 69 units) and the primary somatosensory cortex (S1, 101 units). The precise locations for Th and S1 neurons receiving OS information are reported here for the first time. Interestingly, all recorded nuclei encode modality both at the single neuron and population levels, with noxious stimulation producing a qualitatively different activity profile from other modalities. Moreover, neurons responding to new combinations of stimulus modalities not present in the peripheral TG subsequently appear in Th and S1, being organized in space through the formation of clusters. Besides, neurons that present higher multimodality display higher spontaneous activity. These results constitute the first anatomical and functional characterization of the thalamocortical representation of the OS. Furthermore, they provide insight into how information from different modalities gets integrated from the peripheral nervous system into the complex cortical networks of the brain. KEY POINTS: Anatomical location of thalamic and cortical ocular surface representation. Thalamic and cortical neuronal responses to multimodal stimulation of the ocular surface. Increasing functional complexity along trigeminal neuroaxis. Proposal of a new perspective on how peripheral activity shapes central nervous system function.
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Affiliation(s)
- Enrique Velasco
- Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, San Juan de Alicante, Spain
- Laboratory of Ion Channel Research, VIB-KU Leuven Center for Brain & Disease Research, Leuven, Belgium
- Neuroscience in Physiotherapy (NiP), Independent Research Group, Elche, Spain
- The European University of Brain and Technology, San Juan de Alicante, Spain
| | - Marta Zaforas
- Laboratorio de Neurofisiología Experimental, Unidad de Investigación, Hospital Nacional de Parapléjicos SESCAM, Toledo, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Spain
| | - M Carmen Acosta
- Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, San Juan de Alicante, Spain
- The European University of Brain and Technology, San Juan de Alicante, Spain
| | - Juana Gallar
- Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, San Juan de Alicante, Spain
- The European University of Brain and Technology, San Juan de Alicante, Spain
- Instituto de Investigación Sanitaria y Biomédica de Alicante, San Juan de Alicante, Spain
| | - Juan Aguilar
- Laboratorio de Neurofisiología Experimental, Unidad de Investigación, Hospital Nacional de Parapléjicos SESCAM, Toledo, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Spain
- Grupo de Investigación Multidisciplinar en Cuidados, Facultad de Fisioterapia y Enfermería, Universidad de Castilla-La Mancha, Toledo, Spain
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5
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Marriott BA, Do AD, Portet C, Thellier F, Goutagny R, Jackson J. Brain-state-dependent constraints on claustrocortical communication and function. Cell Rep 2024; 43:113620. [PMID: 38159273 DOI: 10.1016/j.celrep.2023.113620] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 11/20/2023] [Accepted: 12/11/2023] [Indexed: 01/03/2024] Open
Abstract
Neural activity in the claustrum has been associated with a range of vigilance states, yet the activity patterns and efficacy of synaptic communication of identified claustrum neurons have not been thoroughly determined. Here, we show that claustrum neurons projecting to the retrosplenial cortex are most active during synchronized cortical states such as non-rapid eye movement (NREM) sleep and are suppressed during increased cortical desynchronization associated with arousal, movement, and REM sleep. The efficacy of claustrocortical signaling is increased during NREM and diminished during movement due in part to increased cholinergic tone. Finally, claustrum activation during NREM sleep enhances memory consolidation through the phase resetting of cortical delta waves. Therefore, claustrocortical communication is constrained to function most effectively during cognitive processes associated with synchronized cortical states, such as memory consolidation.
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Affiliation(s)
- Brian A Marriott
- Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G2H7, Canada
| | - Alison D Do
- Department of Physiology, University of Alberta, Edmonton, AB T6G2H7, Canada
| | - Coline Portet
- University of Strasbourg, Strasbourg, France; Laboratoire de Neurosciences Cognitives et Adaptatives, CNRS UMR7364, Strasbourg, France
| | - Flora Thellier
- University of Strasbourg, Strasbourg, France; Laboratoire de Neurosciences Cognitives et Adaptatives, CNRS UMR7364, Strasbourg, France
| | - Romain Goutagny
- University of Strasbourg, Strasbourg, France; Laboratoire de Neurosciences Cognitives et Adaptatives, CNRS UMR7364, Strasbourg, France.
| | - Jesse Jackson
- Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G2H7, Canada; Department of Physiology, University of Alberta, Edmonton, AB T6G2H7, Canada.
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6
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Parajuli A, Gutnisky D, Tandon N, Dragoi V. Endogenous fluctuations in cortical state selectively enhance different modes of sensory processing in human temporal lobe. Nat Commun 2023; 14:5591. [PMID: 37696880 PMCID: PMC10495466 DOI: 10.1038/s41467-023-41406-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 08/31/2023] [Indexed: 09/13/2023] Open
Abstract
The degree of synchronized fluctuations in neocortical network activity can vary widely during alertness. One influential idea that has emerged over the past few decades is that perceptual decisions are more accurate when the state of population activity is desynchronized. This suggests that optimal task performance may occur during a particular cortical state - the desynchronized state. Here we show that, contrary to this view, cortical state can both facilitate and suppress perceptual performance in a task-dependent manner. We performed electrical recordings from surface-implanted grid electrodes in the temporal lobe while human subjects completed two perceptual tasks. We found that when local population activity is in a synchronized state, network and perceptual performance are enhanced in a detection task and impaired in a discrimination task, but these modulatory effects are reversed when population activity is desynchronized. These findings indicate that the brain has adapted to take advantage of endogenous fluctuations in the state of neural populations in temporal cortex to selectively enhance different modes of sensory processing during perception in a state-dependent manner.
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Affiliation(s)
- Arun Parajuli
- Department of Neurobiology and Anatomy, McGovern Medical School, University of Texas at Houston, Houston, TX, USA
| | - Diego Gutnisky
- Department of Neurobiology and Anatomy, McGovern Medical School, University of Texas at Houston, Houston, TX, USA
- Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
| | - Nitin Tandon
- Vivian L. Smith Department of Neurosurgery, University of Texas Medical School, Houston, TX, USA
| | - Valentin Dragoi
- Department of Neurobiology and Anatomy, McGovern Medical School, University of Texas at Houston, Houston, TX, USA.
- Department of Electrical and Computer Engineering, Rice University, Houston, TX, USA.
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7
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Buchholz MO, Gastone Guilabert A, Ehret B, Schuhknecht GFP. How synaptic strength, short-term plasticity, and input synchrony contribute to neuronal spike output. PLoS Comput Biol 2023; 19:e1011046. [PMID: 37068099 PMCID: PMC10153727 DOI: 10.1371/journal.pcbi.1011046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Revised: 05/02/2023] [Accepted: 03/24/2023] [Indexed: 04/18/2023] Open
Abstract
Neurons integrate from thousands of synapses whose strengths span an order of magnitude. Intriguingly, in mouse neocortex, the few 'strong' synapses are formed between similarly tuned cells, suggesting they determine spiking output. This raises the question of how other computational primitives, including 'background' activity from the many 'weak' synapses, short-term plasticity, and temporal factors contribute to spiking. We used paired recordings and extracellular stimulation experiments to map excitatory postsynaptic potential (EPSP) amplitudes and paired-pulse ratios of synaptic connections formed between pyramidal neurons in layer 2/3 (L2/3) of barrel cortex. While net short-term plasticity was weak, strong synaptic connections were exclusively depressing. Importantly, we found no evidence for clustering of synaptic properties on individual neurons. Instead, EPSPs and paired-pulse ratios of connections converging onto the same cells spanned the full range observed across L2/3, which critically constrains theoretical models of cortical filtering. To investigate how different computational primitives of synaptic information processing interact to shape spiking, we developed a computational model of a pyramidal neuron in the excitatory L2/3 circuitry, which was constrained by our experiments and published in vivo data. We found that strong synapses were substantially depressed during ongoing activation and their ability to evoke correlated spiking primarily depended on their high temporal synchrony and high firing rates observed in vivo. However, despite this depression, their larger EPSP amplitudes strongly amplified information transfer and responsiveness. Thus, our results contribute to a nuanced framework of how cortical neurons exploit synergies between temporal coding, synaptic properties, and noise to transform synaptic inputs into spikes.
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Affiliation(s)
- Moritz O Buchholz
- Institute of Neuroinformatics, University of Zürich and ETH Zürich Zürich, Switzerland
| | | | - Benjamin Ehret
- Institute of Neuroinformatics, University of Zürich and ETH Zürich Zürich, Switzerland
| | - Gregor F P Schuhknecht
- Institute of Neuroinformatics, University of Zürich and ETH Zürich Zürich, Switzerland
- Department of Molecular and Cellular Biology, Harvard University Cambridge, Massachusetts, United States of America
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8
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Kuo CC, Chan H, Hung WC, Chen RF, Yang HW, Min MY. Carbachol increases locus coeruleus activation by targeting noradrenergic neurons, inhibitory interneurons and inhibitory synaptic transmission. Eur J Neurosci 2023; 57:32-53. [PMID: 36382388 DOI: 10.1111/ejn.15866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 10/11/2022] [Accepted: 11/10/2022] [Indexed: 11/18/2022]
Abstract
The locus coeruleus (LC) consists of noradrenergic (NA) neurons and plays an important role in controlling behaviours. Although much of the knowledge regarding LC functions comes from studying behavioural outcomes upon administration of muscarinic acetylcholine receptor (mAChR) agonists into the nucleus, the exact mechanisms remain unclear. Here, we report that the application of carbachol (CCh), an mAChR agonist, increased the spontaneous action potentials (sAPs) of both LC-NA neurons and local inhibitory interneurons (LC I-INs) in acute brain slices by activating M1/M3 mAChRs (m1/3 AChRs). Optogenetic activation of LC I-INs evoked inhibitory postsynaptic currents (IPSCs) in LC-NA neurons that were mediated by γ-aminobutyric acid type A (GABAA ) and glycine receptors, and CCh application decreased the IPSC amplitude through a presynaptic mechanism by activating M4 mAChRs (m4 AChRs). LC-NA neurons also exhibited spontaneous phasic-like activity (sPLA); CCh application increased the incidence of this activity. This effect of CCh application was not observed with blockade of GABAA and glycine receptors, suggesting that the sPLA enhancement occurred likely because of the decreased synaptic transmission of LC I-INs onto LC-NA neurons by the m4 AChR activation and/or increased spiking rate of LC I-INs by the m1/3 AChR activation, which could lead to fatigue of the synaptic transmission. In conclusion, we report that CCh application, while inhibiting their synaptic transmission, increases sAP rates of LC-NA neurons and LC I-INs. Collectively, these effects provide insight into the cellular mechanisms underlying the behaviour modulations following the administration of muscarinic receptor agonists into the LC reported by the previous studies.
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Affiliation(s)
- Chao-Cheng Kuo
- Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan
| | - Hao Chan
- Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan
| | - Wei-Chen Hung
- Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan
| | - Ruei-Feng Chen
- Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan.,Neurobiology and Cognitive Science Center, National Taiwan University, Taipei, Taiwan
| | - Hsiu-Wen Yang
- Department of Biomedical Sciences, Chung-Shan Medical University, Taichung, Taiwan.,Department of Medical Research, Chung-Shan Medical University Hospital, Taichung, Taiwan
| | - Ming-Yuan Min
- Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan.,Neurobiology and Cognitive Science Center, National Taiwan University, Taipei, Taiwan
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9
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Ou Z, Guo Y, Gharibani P, Slepyan A, Routkevitch D, Bezerianos A, Geocadin RG, Thakor NV. Time-Frequency Analysis of Somatosensory Evoked High-Frequency (600 Hz) Oscillations as an Early Indicator of Arousal Recovery after Hypoxic-Ischemic Brain Injury. Brain Sci 2022; 13:2. [PMID: 36671984 PMCID: PMC9855942 DOI: 10.3390/brainsci13010002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 12/14/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022] Open
Abstract
Cardiac arrest (CA) remains the leading cause of coma, and early arousal recovery indicators are needed to allocate critical care resources properly. High-frequency oscillations (HFOs) of somatosensory evoked potentials (SSEPs) have been shown to indicate responsive wakefulness days following CA. Nonetheless, their potential in the acute recovery phase, where the injury is reversible, has not been tested. We hypothesize that time-frequency (TF) analysis of HFOs can determine arousal recovery in the acute recovery phase. To test our hypothesis, eleven adult male Wistar rats were subjected to asphyxial CA (five with 3-min mild and six with 7-min moderate to severe CA) and SSEPs were recorded for 60 min post-resuscitation. Arousal level was quantified by the neurological deficit scale (NDS) at 4 h. Our results demonstrated that continuous wavelet transform (CWT) of SSEPs localizes HFOs in the TF domain under baseline conditions. The energy dispersed immediately after injury and gradually recovered. We proposed a novel TF-domain measure of HFO: the total power in the normal time-frequency space (NTFS) of HFO. We found that the NTFS power significantly separated the favorable and unfavorable outcome groups. We conclude that the NTFS power of HFOs provides earlier and objective determination of arousal recovery after CA.
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Affiliation(s)
- Ze Ou
- Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Yu Guo
- Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Payam Gharibani
- Departments of Neurology, Division of Neuroimmunology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Ariel Slepyan
- Departments of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Denis Routkevitch
- Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Anastasios Bezerianos
- Information Technologies Institute (ITI), Center for Research and Technology Hellas (CERTH), 57001 Thessaloniki, Greece
| | - Romergryko G. Geocadin
- Departments of Neurology, Anesthesiology, Critical Care Medicine and Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Nitish V. Thakor
- Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
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10
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Polli FS, Kohlmeier KA. Prenatal nicotine alters development of the laterodorsal tegmentum: Possible role for attention-deficit/hyperactivity disorder and drug dependence. World J Psychiatry 2022; 12:212-235. [PMID: 35317337 PMCID: PMC8900586 DOI: 10.5498/wjp.v12.i2.212] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 08/07/2021] [Accepted: 01/14/2022] [Indexed: 02/06/2023] Open
Abstract
As we cycle between the states of wakefulness and sleep, a bilateral cholinergic nucleus in the pontine brain stem, the laterodorsal tegmentum (LDT), plays a critical role in controlling salience processing, attention, behavioral arousal, and electrophysiological signatures of the sub- and microstates of sleep. Disorders involving abnormal alterations in behavioral and motivated states, such as drug dependence, likely involve dysfunctions in LDT signaling. In addition, as the LDT exhibits connectivity with the thalamus and mesocortical circuits, as well as receives direct, excitatory input from the prefrontal cortex, a role for the LDT in cognitive symptoms characterizing attention-deficit/hyperactivity disorder (ADHD) including impulsivity, inflexibility, and dysfunctions of attention is suggested. Prenatal nicotine exposure (PNE) is associated with a higher risk for later life development of drug dependence and ADHD, suggesting alteration in development of brain regions involved in these behaviors. PNE has been shown to alter glutamate and cholinergic signaling within the LDT. As glutamate and acetylcholine are major excitatory mediators, these alterations would likely alter excitatory output to target regions in limbic motivational circuits and to thalamic and cortical networks mediating executive control. Further, PNE alters neuronal development and transmission within prefrontal cortex and limbic areas that send input to the LDT, which would compound effects of differential processing within the PNE LDT. When taken together, alterations in signaling in the LDT are likely to play a role in negative behavioral outcomes seen in PNE individuals, including a heightened risk of drug dependence and ADHD behaviors.
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Affiliation(s)
- Filip S Polli
- Drug Design and Pharmacology, University of Copenhagen, Copenhagen 2100, Denmark
| | - Kristi A Kohlmeier
- Drug Design and Pharmacology, University of Copenhagen, Copenhagen 2100, Denmark
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11
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Wright NC, Borden PY, Liew YJ, Bolus MF, Stoy WM, Forest CR, Stanley GB. Rapid Cortical Adaptation and the Role of Thalamic Synchrony during Wakefulness. J Neurosci 2021; 41:5421-5439. [PMID: 33986072 PMCID: PMC8221593 DOI: 10.1523/jneurosci.3018-20.2021] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 03/18/2021] [Accepted: 04/29/2021] [Indexed: 12/14/2022] Open
Abstract
Rapid sensory adaptation is observed across all sensory systems, and strongly shapes sensory percepts in complex sensory environments. Yet despite its ubiquity and likely necessity for survival, the mechanistic basis is poorly understood. A wide range of primarily in vitro and anesthetized studies have demonstrated the emergence of adaptation at the level of primary sensory cortex, with only modest signatures in earlier stages of processing. The nature of rapid adaptation and how it shapes sensory representations during wakefulness, and thus the potential role in perceptual adaptation, is underexplored, as are the mechanisms that underlie this phenomenon. To address these knowledge gaps, we recorded spiking activity in primary somatosensory cortex (S1) and the upstream ventral posteromedial (VPm) thalamic nucleus in the vibrissa pathway of awake male and female mice, and quantified responses to whisker stimuli delivered in isolation and embedded in an adapting sensory background. We found that cortical sensory responses were indeed adapted by persistent sensory stimulation; putative excitatory neurons were profoundly adapted, and inhibitory neurons only modestly so. Further optogenetic manipulation experiments and network modeling suggest this largely reflects adaptive changes in synchronous thalamic firing combined with robust engagement of feedforward inhibition, with little contribution from synaptic depression. Taken together, these results suggest that cortical adaptation in the regime explored here results from changes in the timing of thalamic input, and the way in which this differentially impacts cortical excitation and feedforward inhibition, pointing to a prominent role of thalamic gating in rapid adaptation of primary sensory cortex.SIGNIFICANCE STATEMENT Rapid adaptation of sensory activity strongly shapes representations of sensory inputs across all sensory pathways over the timescale of seconds, and has profound effects on sensory perception. Despite its ubiquity and theoretical role in the efficient encoding of complex sensory environments, the mechanistic basis is poorly understood, particularly during wakefulness. In this study in the vibrissa pathway of awake mice, we show that cortical representations of sensory inputs are strongly shaped by rapid adaptation, and that this is mediated primarily by adaptive gating of the thalamic inputs to primary sensory cortex and the differential way in which these inputs engage cortical subpopulations of neurons.
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Affiliation(s)
- Nathaniel C Wright
- Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332
| | - Peter Y Borden
- Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332
| | - Yi Juin Liew
- Department of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta, Georgia 30332 and Beijing University, Beijing China 100871
| | - Michael F Bolus
- Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332
| | - William M Stoy
- Department of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332
| | - Craig R Forest
- Department of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332
| | - Garrett B Stanley
- Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332
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12
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Neurophysiological basis of the N400 deflection, from Mismatch Negativity to Semantic Prediction Potentials and late positive components. Int J Psychophysiol 2021; 166:134-150. [PMID: 34097935 DOI: 10.1016/j.ijpsycho.2021.06.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 05/20/2021] [Accepted: 06/02/2021] [Indexed: 11/21/2022]
Abstract
The first theoretical model on the neurophysiological basis of the N400: the deflection reflects layer I dendritic plateaus on a preparatory state of synaptic integration that precedes layer V somatic burst firing for conscious identification of the higher-order features of the stimulus (a late positive shift). Plateaus ensue from apical disinhibition by vasoactive intestinal polypeptide-positive interneurons (VIPs) through suppression of Martinotti cells, opening the gates for glutamatergic feedback to trigger dendritic regenerative potentials. Cholinergic transients contribute to these dynamics directly, holding a central role in the N400 deflection. The stereotypical timing of the (frontal) glutamatergic feedback and the accompanying cholinergic transients account for the enigmatic "invariability" of the peak latency in the face of a gamut of different stimuli and paradigms. The theoretical postulations presented here may bring about unprecedented level of detail for the N400 deflection to be used in the study of schizophrenia, Alzheimer's disease and other higher-order pathologies. The substrates of a late positive component, the Mismatch Negativity and the Semantic Prediction Potentials are also surveyed.
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13
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Zou G, Xu J, Zhou S, Liu J, Su ZH, Zou Q, Gao JH. Functional MRI of arousals in nonrapid eye movement sleep. Sleep 2021; 43:5573984. [PMID: 31555827 DOI: 10.1093/sleep/zsz218] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 07/26/2019] [Indexed: 11/13/2022] Open
Abstract
Arousals commonly occur during human sleep and have been associated with several sleep disorders. Arousals are characterized as an abrupt electroencephalography (EEG) frequency change to higher frequencies during sleep. However, the human brain regions involved in arousal are not yet clear. Simultaneous EEG and functional magnetic resonance imaging (fMRI) data were recorded during the early portion of the sleep period in healthy young adults. Arousals were identified based on the EEG data, and fMRI signal changes associated with 83 arousals from 19 subjects were analyzed. Subcortical regions, including the midbrain, thalamus, basal ganglia, and cerebellum, were activated with arousal. Cortices, including the temporal gyrus, occipital gyrus, and frontal gyrus, were deactivated with arousal. The activations associated with arousal in the subcortical regions were consistent with previous findings of subcortical involvement in behavioral arousal and consciousness. Cortical deactivations may serve as a mechanism to direct incoming sensory stimuli to specific brain regions, thereby monitoring environmental perturbations during sleep.
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Affiliation(s)
- Guangyuan Zou
- Beijing City Key Lab for Medical Physics and Engineering, Institution of Heavy Ion Physics, School of Physics, Peking University, Beijing, China.,Center for MRI Research, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
| | - Jing Xu
- Laboratory of Applied Brain and Cognitive Sciences, College of International Business, Shanghai International Studies University, Shanghai, China
| | - Shuqin Zhou
- Center for MRI Research, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.,Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, China
| | - Jiayi Liu
- Beijing City Key Lab for Medical Physics and Engineering, Institution of Heavy Ion Physics, School of Physics, Peking University, Beijing, China.,Center for MRI Research, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
| | - Zi Hui Su
- Center for MRI Research, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.,Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, United Kingdom
| | - Qihong Zou
- Center for MRI Research, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
| | - Jia-Hong Gao
- Beijing City Key Lab for Medical Physics and Engineering, Institution of Heavy Ion Physics, School of Physics, Peking University, Beijing, China.,Center for MRI Research, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.,McGovern Institute for Brain Research, Peking University, Beijing, China.,Shenzhen Institute of Neuroscience, Shenzhen, China
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14
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Gasselin C, Hohl B, Vernet A, Crochet S, Petersen CCH. Cell-type-specific nicotinic input disinhibits mouse barrel cortex during active sensing. Neuron 2021; 109:778-787.e3. [PMID: 33472037 PMCID: PMC7927912 DOI: 10.1016/j.neuron.2020.12.018] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 11/24/2020] [Accepted: 12/21/2020] [Indexed: 12/14/2022]
Abstract
Fast synaptic transmission relies upon the activation of ionotropic receptors by neurotransmitter release to evoke postsynaptic potentials. Glutamate and GABA play dominant roles in driving highly dynamic activity in synaptically connected neuronal circuits, but ionotropic receptors for other neurotransmitters are also expressed in the neocortex, including nicotinic receptors, which are non-selective cation channels gated by acetylcholine. To study the function of non-glutamatergic excitation in neocortex, we used two-photon microscopy to target whole-cell membrane potential recordings to different types of genetically defined neurons in layer 2/3 of primary somatosensory barrel cortex in awake head-restrained mice combined with pharmacological and optogenetic manipulations. Here, we report a prominent nicotinic input, which selectively depolarizes a subtype of GABAergic neuron expressing vasoactive intestinal peptide leading to disinhibition during active sensorimotor processing. Nicotinic disinhibition of somatosensory cortex during active sensing might contribute importantly to integration of top-down and motor-related signals necessary for tactile perception and learning.
Acetylcholine is released in the mouse barrel cortex during active whisker sensing Acetylcholine depolarizes inhibitory cells expressing vasoactive intestinal peptide Excitation of vasoactive intestinal peptide-expressing neurons causes disinhibition Cholinergic-driven disinhibition could gate sensorimotor integration and plasticity
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Affiliation(s)
- Célia Gasselin
- Laboratory of Sensory Processing, Brain Mind Institute, Faculty of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
| | - Benoît Hohl
- Laboratory of Sensory Processing, Brain Mind Institute, Faculty of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
| | - Arthur Vernet
- Laboratory of Sensory Processing, Brain Mind Institute, Faculty of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
| | - Sylvain Crochet
- Laboratory of Sensory Processing, Brain Mind Institute, Faculty of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
| | - Carl C H Petersen
- Laboratory of Sensory Processing, Brain Mind Institute, Faculty of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
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15
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Staiger JF, Petersen CCH. Neuronal Circuits in Barrel Cortex for Whisker Sensory Perception. Physiol Rev 2020; 101:353-415. [PMID: 32816652 DOI: 10.1152/physrev.00019.2019] [Citation(s) in RCA: 72] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The array of whiskers on the snout provides rodents with tactile sensory information relating to the size, shape and texture of objects in their immediate environment. Rodents can use their whiskers to detect stimuli, distinguish textures, locate objects and navigate. Important aspects of whisker sensation are thought to result from neuronal computations in the whisker somatosensory cortex (wS1). Each whisker is individually represented in the somatotopic map of wS1 by an anatomical unit named a 'barrel' (hence also called barrel cortex). This allows precise investigation of sensory processing in the context of a well-defined map. Here, we first review the signaling pathways from the whiskers to wS1, and then discuss current understanding of the various types of excitatory and inhibitory neurons present within wS1. Different classes of cells can be defined according to anatomical, electrophysiological and molecular features. The synaptic connectivity of neurons within local wS1 microcircuits, as well as their long-range interactions and the impact of neuromodulators, are beginning to be understood. Recent technological progress has allowed cell-type-specific connectivity to be related to cell-type-specific activity during whisker-related behaviors. An important goal for future research is to obtain a causal and mechanistic understanding of how selected aspects of tactile sensory information are processed by specific types of neurons in the synaptically connected neuronal networks of wS1 and signaled to downstream brain areas, thus contributing to sensory-guided decision-making.
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Affiliation(s)
- Jochen F Staiger
- University Medical Center Göttingen, Institute for Neuroanatomy, Göttingen, Germany; and Laboratory of Sensory Processing, Faculty of Life Sciences, Brain Mind Institute, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
| | - Carl C H Petersen
- University Medical Center Göttingen, Institute for Neuroanatomy, Göttingen, Germany; and Laboratory of Sensory Processing, Faculty of Life Sciences, Brain Mind Institute, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
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16
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Laliberté G, Othman R, Vaucher E. Mesoscopic Mapping of Stimulus-Selective Response Plasticity in the Visual Pathways Modulated by the Cholinergic System. Front Neural Circuits 2020; 14:38. [PMID: 32719589 PMCID: PMC7350895 DOI: 10.3389/fncir.2020.00038] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Accepted: 05/22/2020] [Indexed: 11/13/2022] Open
Abstract
The cholinergic potentiation of visual conditioning enhances visual acuity and discrimination of the trained stimulus. To determine if this also induces long-term plastic changes on cortical maps and connectivity in the visual cortex and higher associative areas, mesoscopic calcium imaging was performed in head-fixed awake GCaMP6s adult mice before and after conditioning. The conditioned stimulus (0.03 cpd, 30°, 100% contrast, 1 Hz-drifting gratings) was presented 10 min daily for a week. Saline or Donepezil (DPZ, 0.3 mg/kg, s.c.), a cholinesterase inhibitor that potentiates cholinergic transmission, were injected prior to each conditioning session and compared to a sham-conditioned group. Cortical maps of resting state and evoked response to the monocular presentation of conditioned or non-conditioned stimulus (30°, 50 and 75% contrast; 90°, 50, 75, and 100% contrast) were established. Amplitude, duration, and latency of the peak response, as well as size of activation were measured in the primary visual cortex (V1), secondary visual areas (AL, A, AM, PM, LM, RL), retrosplenial cortex (RSC), and higher cortical areas. Visual stimulation increased calcium signaling in all primary and secondary visual areas, the RSC, but no other cortices. There were no significant effects of sham-conditioning or conditioning alone, but DPZ treatment during conditioning significantly decreased the integrated neuronal activity of superficial layers evoked by the conditioned stimulus in V1, AL, PM, and LM. The activity of downstream cortical areas was not changed. The size of the activated area was decreased in V1 and PM, and the signal-to-noise ratio was decreased in AL and PM. Interestingly, signal correlation was seen only between V1, the ventral visual pathway, and the RSC, and was decreased by DPZ administration. The resting state activity was slightly correlated and rarely affected by treatments, except between binocular and monocular V1 in both hemispheres. In conclusion, cholinergic potentiation of visual conditioning induced change in visual processing in the superficial cortical layers. This effect might be a key mechanism in the establishment of the fine cortical tuning in response to the conditioned visual stimulus.
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Affiliation(s)
- Guillaume Laliberté
- Laboratoire de Neurobiologie de la Cognition Visuelle, École d'Optométrie, Université de Montréal, Montréal, QC, Canada
| | - Rahmeh Othman
- Laboratoire de Neurobiologie de la Cognition Visuelle, École d'Optométrie, Université de Montréal, Montréal, QC, Canada.,Départment de Pharmacologie et Physiologie, Faculté de Médecine, Université de Montréal, Montréal, QC, Canada
| | - Elvire Vaucher
- Laboratoire de Neurobiologie de la Cognition Visuelle, École d'Optométrie, Université de Montréal, Montréal, QC, Canada
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17
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Pauzin FP, Schwarz N, Krieger P. Activation of Corticothalamic Layer 6 Cells Decreases Angular Tuning in Mouse Barrel Cortex. Front Neural Circuits 2019; 13:67. [PMID: 31736714 PMCID: PMC6838007 DOI: 10.3389/fncir.2019.00067] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Accepted: 09/30/2019] [Indexed: 01/21/2023] Open
Abstract
In the mouse whisker system, the contribution of L6 corticothalamic cells (L6 CT) to cortical and thalamic processing of the whisker deflection direction was investigated. A genetically defined population of L6 CT cells project to infragranular GABAergic interneurons that hyperpolarize neurons in somatosensory barrel cortex (BC). Optogenetic activation of these neurons switched BC to an adapted mode in which excitatory cells lost their angular tuning. In contrast, however, this was not the case with a general activation of inhibitory interneurons via optogenetic activation of Gad2-expressing cells. The decrease in angular tuning, when L6 CT cells were activated, was due to changes in cortical inhibition, and not inherited from changes in the thalamic output. Furthermore, L6 CT driven cortical inhibition, but not the general activation of GABAergic interneurons, abolished adaptation to whisker responses. In the present study, evidence is presented that a subpopulation of L6 CT activates a specific circuit of GABAergic interneurons that will predispose neocortex toward processing of tactile information requiring multiple whisker touches, such as in a texture discrimination task.
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Affiliation(s)
- François Philippe Pauzin
- Department of Systems Neuroscience, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany
| | - Nadja Schwarz
- Department of Systems Neuroscience, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany
| | - Patrik Krieger
- Department of Systems Neuroscience, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany
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18
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Enhanced Thalamocortical Synaptic Transmission and Dysregulation of the Excitatory-Inhibitory Balance at the Thalamocortical Feedforward Inhibitory Microcircuit in a Genetic Mouse Model of Migraine. J Neurosci 2019; 39:9841-9851. [PMID: 31645463 DOI: 10.1523/jneurosci.1840-19.2019] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Revised: 09/05/2019] [Accepted: 09/22/2019] [Indexed: 12/22/2022] Open
Abstract
Migraine is a complex brain disorder, characterized by attacks of unilateral headache and global dysfunction in multisensory information processing, whose underlying cellular and circuit mechanisms remain unknown. The finding of enhanced excitatory, but unaltered inhibitory, neurotransmission at intracortical synapses in mouse models of familial hemiplegic migraine (FHM) suggested the hypothesis that dysregulation of the excitatory-inhibitory balance in specific circuits is a key pathogenic mechanism. Here, we investigated the thalamocortical (TC) feedforward inhibitory microcircuit in FHM1 mice of both sexes carrying a gain-of-function mutation in CaV2.1. We show that TC synaptic transmission in somatosensory cortex is enhanced in FHM1 mice. Due to similar gain of function of TC excitation of layer 4 excitatory and fast-spiking inhibitory neurons elicited by single thalamic stimulations, neither the excitatory-inhibitory balance nor the integration time window set by the TC feedforward inhibitory microcircuit was altered in FHM1 mice. However, during repetitive thalamic stimulation, the typical shift of the excitatory-inhibitory balance toward excitation and the widening of the integration time window were both smaller in FHM1 compared with WT mice, revealing a dysregulation of the excitatory-inhibitory balance, whereby the balance is relatively skewed toward inhibition. This is due to an unexpected differential effect of the FHM1 mutation on short-term synaptic plasticity at TC synapses on cortical excitatory and fast-spiking inhibitory neurons. Our findings point to enhanced transmission of sensory, including trigeminovascular nociceptive, signals from thalamic nuclei to cortex and TC excitatory-inhibitory imbalance as mechanisms that may contribute to headache, increased sensory gain, and sensory processing dysfunctions in migraine.SIGNIFICANCE STATEMENT Migraine is a complex brain disorder, characterized by attacks of unilateral headache and by global dysfunction in multisensory information processing, whose underlying cellular and circuit mechanisms remain unknown. Here we provide insights into these mechanisms by investigating thalamocortical (TC) synaptic transmission and the function of the TC feedforward inhibitory microcircuit in a mouse model of a rare monogenic migraine. This microcircuit is critical for gating information flow to cortex and for sensory processing. We reveal increased TC transmission and dysregulation of the cortical excitatory-inhibitory balance set by the TC feedforward inhibitory microcircuit, whereby the balance is relatively skewed toward inhibition during repetitive thalamic activity. These alterations may contribute to headache, increased sensory gain, and sensory processing dysfunctions in migraine.
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19
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Bolus MF, Willats AA, Whitmire CJ, Rozell CJ, Stanley GB. Design strategies for dynamic closed-loop optogenetic neurocontrol in vivo. J Neural Eng 2019; 15:026011. [PMID: 29300002 DOI: 10.1088/1741-2552/aaa506] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVE Controlling neural activity enables the possibility of manipulating sensory perception, cognitive processes, and body movement, in addition to providing a powerful framework for functionally disentangling the neural circuits that underlie these complex phenomena. Over the last decade, optogenetic stimulation has become an increasingly important and powerful tool for understanding neural circuit function, owing to the ability to target specific cell types and bidirectionally modulate neural activity. To date, most stimulation has been provided in open-loop or in an on/off closed-loop fashion, where previously-determined stimulation is triggered by an event. Here, we describe and demonstrate a design approach for precise optogenetic control of neuronal firing rate modulation using feedback to guide stimulation continuously. APPROACH Using the rodent somatosensory thalamus as an experimental testbed for realizing desired time-varying patterns of firing rate modulation, we utilized a moving average exponential filter to estimate firing rate online from single-unit spiking measured extracellularly. This estimate of instantaneous rate served as feedback for a proportional integral (PI) controller, which was designed during the experiment based on a linear-nonlinear Poisson (LNP) model of the neuronal response to light. MAIN RESULTS The LNP model fit during the experiment enabled robust closed-loop control, resulting in good tracking of sinusoidal and non-sinusoidal targets, and rejection of unmeasured disturbances. Closed-loop control also enabled manipulation of trial-to-trial variability. SIGNIFICANCE Because neuroscientists are faced with the challenge of dissecting the functions of circuit components, the ability to maintain control of a region of interest in spite of changes in ongoing neural activity will be important for disambiguating function within networks. Closed-loop stimulation strategies are ideal for control that is robust to such changes, and the employment of continuous feedback to adjust stimulation in real-time can improve the quality of data collected using optogenetic manipulation.
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Affiliation(s)
- M F Bolus
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, United States of America
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20
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Adibi M. Whisker-Mediated Touch System in Rodents: From Neuron to Behavior. Front Syst Neurosci 2019; 13:40. [PMID: 31496942 PMCID: PMC6712080 DOI: 10.3389/fnsys.2019.00040] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Accepted: 08/02/2019] [Indexed: 01/02/2023] Open
Abstract
A key question in systems neuroscience is to identify how sensory stimuli are represented in neuronal activity, and how the activity of sensory neurons in turn is “read out” by downstream neurons and give rise to behavior. The choice of a proper model system to address these questions, is therefore a crucial step. Over the past decade, the increasingly powerful array of experimental approaches that has become available in non-primate models (e.g., optogenetics and two-photon imaging) has spurred a renewed interest for the use of rodent models in systems neuroscience research. Here, I introduce the rodent whisker-mediated touch system as a structurally well-established and well-organized model system which, despite its simplicity, gives rise to complex behaviors. This system serves as a behaviorally efficient model system; known as nocturnal animals, along with their olfaction, rodents rely on their whisker-mediated touch system to collect information about their surrounding environment. Moreover, this system represents a well-studied circuitry with a somatotopic organization. At every stage of processing, one can identify anatomical and functional topographic maps of whiskers; “barrelettes” in the brainstem nuclei, “barreloids” in the sensory thalamus, and “barrels” in the cortex. This article provides a brief review on the basic anatomy and function of the whisker system in rodents.
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Affiliation(s)
- Mehdi Adibi
- School of Psychology, University of New South Wales, Sydney, NSW, Australia.,Tactile Perception and Learning Lab, International School for Advanced Studies (SISSA), Trieste, Italy.,Padua Neuroscience Center, University of Padua, Padua, Italy
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21
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Abstract
Tactile sensory information from facial whiskers provides nocturnal tunnel-dwelling rodents, including mice and rats, with important spatial and textural information about their immediate surroundings. Whiskers are moved back and forth to scan the environment (whisking), and touch signals from each whisker evoke sparse patterns of neuronal activity in whisker-related primary somatosensory cortex (wS1; barrel cortex). Whisking is accompanied by desynchronized brain states and cell-type-specific changes in spontaneous and evoked neuronal activity. Tactile information, including object texture and location, appears to be computed in wS1 through integration of motor and sensory signals. wS1 also directly controls whisker movements and contributes to learned, whisker-dependent, goal-directed behaviours. The cell-type-specific neuronal circuitry in wS1 that contributes to whisker sensory perception is beginning to be defined.
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22
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Bereshpolova Y, Stoelzel CR, Su C, Alonso JM, Swadlow HA. Activation of a Visual Cortical Column by a Directionally Selective Thalamocortical Neuron. Cell Rep 2019; 27:3733-3740.e3. [PMID: 31242407 DOI: 10.1016/j.celrep.2019.05.094] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Revised: 05/07/2019] [Accepted: 05/22/2019] [Indexed: 01/26/2023] Open
Abstract
The retinas of rabbits and rodents have directionally selective (DS) retinal ganglion cells that convey directional signals through the lateral geniculate nucleus (LGN) of the thalamus to the primary visual cortex (V1). Notably, the function and synaptic impact in V1 of these directional LGN signals are unknown. Here we measured, in awake rabbits, the synaptic impact generated in V1 by individual LGN DS neurons. We show that these neurons make fast and strong connections in layers 4 and 6, with postsynaptic effects that are similar to those made by LGN concentric neurons, the main thalamic drivers of V1. By contrast, the synaptic impact of LGN DS neurons on superficial cortical layers was not detectable. These results suggest that LGN DS neurons activate a cortical column by targeting the main cortical input layers and that the role of DS input to superficial cortical layers is likely to be weak and/or modulatory.
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Affiliation(s)
- Yulia Bereshpolova
- Department of Psychological Sciences, University of Connecticut, Storrs, CT 06269, USA
| | - Carl R Stoelzel
- Department of Psychological Sciences, University of Connecticut, Storrs, CT 06269, USA
| | - Chuyi Su
- Department of Psychological Sciences, University of Connecticut, Storrs, CT 06269, USA
| | - Jose-Manuel Alonso
- Department of Psychological Sciences, University of Connecticut, Storrs, CT 06269, USA; Department of Biological and Vision Sciences, State University of New York College of Optometry, New York, NY 10036, USA
| | - Harvey A Swadlow
- Department of Psychological Sciences, University of Connecticut, Storrs, CT 06269, USA; Department of Biological and Vision Sciences, State University of New York College of Optometry, New York, NY 10036, USA.
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23
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Optogenetic reactivation of memory ensembles in the retrosplenial cortex induces systems consolidation. Proc Natl Acad Sci U S A 2019; 116:8576-8581. [PMID: 30877252 DOI: 10.1073/pnas.1818432116] [Citation(s) in RCA: 88] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
The neural circuits underlying memory change over prolonged periods after learning, in a process known as systems consolidation. Postlearning spontaneous reactivation of memory-related neural ensembles is thought to mediate this process, although a causal link has not been established. Here we test this hypothesis in mice by using optogenetics to selectively reactivate neural ensembles representing a contextual fear memory (sometimes referred to as engram neurons). High-frequency stimulation of these ensembles in the retrosplenial cortex 1 day after learning produced a recent memory with features normally observed in consolidated remote memories, including higher engagement of neocortical areas during retrieval, contextual generalization, and decreased hippocampal dependence. Moreover, this effect was only present if memory ensembles were reactivated during sleep or light anesthesia. These results provide direct support for postlearning memory ensemble reactivation as a mechanism of systems consolidation, and show that this process can be accelerated by ensemble reactivation in an unconscious state.
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24
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Poulet JFA, Crochet S. The Cortical States of Wakefulness. Front Syst Neurosci 2019; 12:64. [PMID: 30670952 PMCID: PMC6331430 DOI: 10.3389/fnsys.2018.00064] [Citation(s) in RCA: 70] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Accepted: 12/11/2018] [Indexed: 11/15/2022] Open
Abstract
Cortical neurons process information on a background of spontaneous, ongoing activity with distinct spatiotemporal profiles defining different cortical states. During wakefulness, cortical states alter constantly in relation to behavioral context, attentional level or general motor activity. In this review article, we will discuss our current understanding of cortical states in awake rodents, how they are controlled, their impact on sensory processing, and highlight areas for future research. A common observation in awake rodents is the rapid change in spontaneous cortical activity from high-amplitude, low-frequency (LF) fluctuations, when animals are quiet, to faster and smaller fluctuations when animals are active. This transition is typically thought of as a change in global brain state but recent work has shown variation in cortical states across regions, indicating the presence of a fine spatial scale control system. In sensory areas, the cortical state change is mediated by at least two convergent inputs, one from the thalamus and the other from cholinergic inputs in the basal forebrain. Cortical states have a major impact on the balance of activity between specific subtypes of neurons, on the synchronization between nearby neurons, as well as the functional coupling between distant cortical areas. This reorganization of the activity of cortical networks strongly affects sensory processing. Thus cortical states provide a dynamic control system for the moment-by-moment regulation of cortical processing.
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Affiliation(s)
- James F. A. Poulet
- Neural Circuits and Behaviour, Department of Neuroscience, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany
- Neuroscience Research Center and Cluster of Excellence NeuroCure, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Sylvain Crochet
- Laboratory of Sensory Processing, Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
- Lyon Neuroscience Research Center, INSERM U1028/CNRS UMR5292, University Lyon 1, Lyon, France
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25
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Vinokurova D, Zakharov AV, Lebedeva J, Burkhanova GF, Chernova KA, Lotfullina N, Khazipov R, Valeeva G. Pharmacodynamics of the Glutamate Receptor Antagonists in the Rat Barrel Cortex. Front Pharmacol 2018; 9:698. [PMID: 30018551 PMCID: PMC6038834 DOI: 10.3389/fphar.2018.00698] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2018] [Accepted: 06/08/2018] [Indexed: 02/01/2023] Open
Abstract
Epipial application is one of the approaches for drug delivery into the cortex. However, passive diffusion of epipially applied drugs through the cortical depth may be slow, and different drug concentrations may be achieved at different rates across the cortical depth. Here, we explored the pharmacodynamics of the inhibitory effects of epipially applied ionotropic glutamate receptor antagonists CNQX and dAPV on sensory-evoked and spontaneous activity across layers of the cortical barrel column in urethane-anesthetized rats. The inhibitory effects of CNQX and dAPV were observed at concentrations that were an order higher than in slices in vitro, and they slowly developed from the cortical surface to depth after epipial application. The level of the inhibitory effects also followed the surface-to-depth gradient, with full inhibition of sensory evoked potentials (SEPs) in the supragranular layers and L4 and only partial inhibition in L5 and L6. During epipial CNQX and dAPV application, spontaneous activity and the late component of multiple unit activity (MUA) during sensory-evoked responses were suppressed faster than the short-latency MUA component. Despite complete suppression of SEPs in L4, sensory-evoked short-latency multiunit responses in L4 persisted, and they were suppressed by further addition of lidocaine suggesting that spikes in thalamocortical axons contribute ∼20% to early multiunit responses. Epipial CNQX and dAPV also completely suppressed sensory-evoked very fast (∼500 Hz) oscillations and spontaneous slow wave activity in L2/3 and L4. However, delta oscillations persisted in L5/6. Thus, CNQX and dAPV exert inhibitory actions on cortical activity during epipial application at much higher concentrations than in vitro, and the pharmacodynamics of their inhibitory effects is characterized by the surface-to-depth gradients in the rate of development and the level of inhibition of sensory-evoked and spontaneous cortical activity.
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Affiliation(s)
- Daria Vinokurova
- Laboratory of Neurobiology, Kazan Federal University, Kazan, Russia.,Mediterranean Institute of Neurobiology - National Institute of Health and Medical Research, Aix-Marseille University, UMR1249, Marseille, France
| | | | - Julia Lebedeva
- Laboratory of Neurobiology, Kazan Federal University, Kazan, Russia
| | | | | | - Nailya Lotfullina
- Laboratory of Neurobiology, Kazan Federal University, Kazan, Russia.,Mediterranean Institute of Neurobiology - National Institute of Health and Medical Research, Aix-Marseille University, UMR1249, Marseille, France
| | - Rustem Khazipov
- Laboratory of Neurobiology, Kazan Federal University, Kazan, Russia.,Mediterranean Institute of Neurobiology - National Institute of Health and Medical Research, Aix-Marseille University, UMR1249, Marseille, France
| | - Guzel Valeeva
- Laboratory of Neurobiology, Kazan Federal University, Kazan, Russia
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26
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Neural Coding of Whisker-Mediated Touch in Primary Somatosensory Cortex Is Altered Following Early Blindness. J Neurosci 2018; 38:6172-6189. [PMID: 29807911 DOI: 10.1523/jneurosci.0066-18.2018] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2018] [Revised: 05/20/2018] [Accepted: 05/23/2018] [Indexed: 10/14/2022] Open
Abstract
Sensory systems do not develop and function independently of one another, yet they are typically studied in isolation. Effects of multisensory interactions on the developing neocortex can be revealed by altering the ratios of incoming sensory inputs associated with different modalities. We investigated neural responses in primary somatosensory cortex (S1) of short-tailed opossums (Monodelphis domestica; either sex) after the elimination of visual input through bilateral enucleation very early in development. To assess the influence of tactile experience after vision loss, we also examined naturally occurring patterns of exploratory behavior. In early blind (EB) animals, overall levels of tactile experience were similar to those of sighted controls (SC); locomotor activity was unimpaired and accompanied by whisking. Using extracellular single-unit recording techniques under anesthesia, we found that EB animals exhibited a reduction in the magnitude of neural responses to whisker stimuli in S1, coupled with spatial sharpening of receptive fields, in comparison to SC animals. These alterations manifested as two different effects on sensory processing in S1 of EB animals: the ability of neurons to detect single whisker stimulation was decreased, whereas their ability to discriminate between stimulation of neighboring whiskers was enhanced. The increased selectivity of S1 neurons in EB animals was reflected in improved population decoding performance for whisker stimulus position, particularly along the rostrocaudal axis of the snout, which aligns with the primary axis of natural whisker motion. These findings suggest that a functionally distinct form of somatosensory plasticity occurs when vision is lost early in development.SIGNIFICANCE STATEMENT After sensory loss, compensatory behavior mediated through the spared senses could be generated entirely through the recruitment of brain areas associated with the deprived sense. Alternatively, functional compensation in spared modalities may be achieved through a combination of plasticity in brain areas corresponding to both spared and deprived sensory modalities. Although activation of neurons in cortex associated with a deprived sense has been described frequently, it is unclear whether this is the only substrate available for compensation or if plasticity within cortical fields corresponding to spared modalities, particularly primary sensory cortices, may also contribute. Here, we demonstrate empirically that early loss of vision alters coding of sensory inputs in primary somatosensory cortex in a manner that supports enhanced tactile discrimination.
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Hetherington L, Dommett EJ, Turner AC, Riley TB, Haensel JX, Overton PG. Effect of methylphenidate on visual responses in the superior colliculus in the anaesthetised rat: Role of cortical activation. J Psychopharmacol 2017; 31:1347-1361. [PMID: 28925314 DOI: 10.1177/0269881117730661] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
The mechanism of action of psychostimulant drugs in the treatment of Attention Deficit Hyperactivity Disorder is still largely unknown, although recent evidence suggests one possibility is that the drugs affect the superior colliculus (SC). We have previously demonstrated that systemically administered d-amphetamine attenuates/abolishes visual responses to wholefield light flashes in the superficial layers of the SC in anaesthetised rats, and the present study sought to extend this work to methylphenidate (MPH). Anaesthetised rats were administered MPH at a range of doses (or saline) and subjected to monocular wholefield light flashes at two intensities, juxta-threshold and super-threshold. In contrast to d-amphetamine, systemic MPH produced an enhancement of visual activity at both intensities. Methylphenidate was also found to produce activation of the cortical EEG in anaesthetised rats. Furthermore, cortical activation induced by electrical stimulation of the pons was found to enhance visual responses in superficial layers of the SC, and when MPH was paired with pontine-induced cortical activation, the response-enhancing effects of MPH were substantially attenuated. Taken together, the results suggest that the enhancement of visual responses in the superficial layers of the SC by MPH in the anaesthetised rat is an artefact of the drug's interaction with cortical arousal.
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Affiliation(s)
- L Hetherington
- 1 Department of Psychology, University of Sheffield, Sheffield, UK
| | - E J Dommett
- 2 Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - A C Turner
- 3 School of Life, Health and Chemical Sciences, The Open University, Milton Keynes, UK
| | - T B Riley
- 1 Department of Psychology, University of Sheffield, Sheffield, UK
| | - J X Haensel
- 4 Department of Psychological Sciences, Birkbeck, University of London, London, UK
| | - P G Overton
- 1 Department of Psychology, University of Sheffield, Sheffield, UK
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28
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Casas-Torremocha D, Clascá F, Núñez Á. Posterior Thalamic Nucleus Modulation of Tactile Stimuli Processing in Rat Motor and Primary Somatosensory Cortices. Front Neural Circuits 2017; 11:69. [PMID: 29021744 PMCID: PMC5623691 DOI: 10.3389/fncir.2017.00069] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Accepted: 09/12/2017] [Indexed: 12/18/2022] Open
Abstract
Rodents move rhythmically their facial whiskers and compute differences between signals predicted and those resulting from the movement to infer information about objects near their head. These computations are carried out by a large network of forebrain structures that includes the thalamus and the primary somatosensory (S1BF) and motor (M1wk) cortices. Spatially and temporally precise mechanorreceptive whisker information reaches the S1BF cortex via the ventroposterior medial thalamic nucleus (VPM). Other whisker-related information may reach both M1wk and S1BF via the axons from the posterior thalamic nucleus (Po). However, Po axons may convey, in addition to direct sensory signals, the dynamic output of computations between whisker signals and descending motor commands. It has been proposed that this input may be relevant for adjusting cortical responses to predicted vs. unpredicted whisker signals, but the effects of Po input on M1wk and S1BF function have not been directly tested or compared in vivo. Here, using electrophysiology, optogenetics and pharmacological tools, we compared in adult rats M1wk and S1BF in vivo responses in the whisker areas of the motor and primary somatosensory cortices to passive multi-whisker deflection, their dependence on Po activity, and their changes after a brief intense activation of Po axons. We report that the latencies of the first component of tactile-evoked local field potentials in M1wk and S1BF are similar. The evoked potentials decrease markedly in M1wk, but not in S1BF, by injection in Po of the GABAA agonist muscimol. A brief high-frequency electrical stimulation of Po decreases the responsivity of M1wk and S1BF cells to subsequent whisker stimulation. This effect is prevented by the local application of omega-agatoxin, suggesting that it may in part depend on GABA release by fast-spiking parvalbumin (PV)-expressing cortical interneurons. Local optogenetic activation of Po synapses in different cortical layers also diminishes M1wk and S1BF responses. This effect is most pronounced in the superficial layers of both areas, known to be the main source and target of their reciprocal cortico-cortical connections.
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Affiliation(s)
- Diana Casas-Torremocha
- Department of Anatomy, Histology and Neuroscience, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain
| | - Francisco Clascá
- Department of Anatomy, Histology and Neuroscience, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain
| | - Ángel Núñez
- Department of Anatomy, Histology and Neuroscience, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain
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29
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Differential Excitation of Distally versus Proximally Targeting Cortical Interneurons by Unitary Thalamocortical Bursts. J Neurosci 2017; 36:6906-16. [PMID: 27358449 DOI: 10.1523/jneurosci.0739-16.2016] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2016] [Accepted: 05/16/2016] [Indexed: 12/18/2022] Open
Abstract
UNLABELLED Thalamocortical neurons relay sensory and motor information to the neocortex using both single spikes and bursts; bursts prevail during low-vigilance states but also occur during awake behavior. Bursts are suggested to provide an alerting signal to the cortex and enhance stimulus detection, but the synaptic mechanisms underlying these effects are not clear, because the postsynaptic responses of different subtypes of cortical neurons to unitary thalamocortical bursts are mostly unknown. Using optogenetically guided recordings in mouse thalamocortical slices, we achieved the first reported paired intracellular recordings from nine monosynaptically connected thalamic and cortical neurons, including principal cells and two subtypes of inhibitory interneurons, and compared between cortical responses to single thalamocortical spikes and bursts. In 18 additional cortical neurons, we elicited unitary burst responses optogenetically. Short-term dynamics and temporal summation of burst-evoked EPSPs were cell-type dependent: in principal cells and somatostatin-containing (SOM), but not fast-spiking (FS), interneurons, peak response during a burst was on average more than twofold larger than the response to the first spike. Thus, firing a burst instead of a single spike would more than double the probability of firing in postsynaptic excitatory neurons and in SOM, but not FS, interneurons. Consistent with this prediction, FS interneurons held near firing threshold fired most often on the first burst component, whereas SOM interneurons fired only on the second or later components. By increasing excitation of principal cells together with SOM-mediated, distally directed inhibition, thalamocortical bursts could momentarily enhance the saliency of the ascending sensory stimulus over less urgent, top-down inputs. SIGNIFICANCE STATEMENT Thalamocortical neurons relay sensory and motor information to the cerebral cortex using both single spikes and high-frequency bursts, but the function of bursts is not fully understood. Using brain slices from mouse somatosensory thalamus and cortex, we achieved the first dual recordings of directly connected thalamic and cortical neurons and compared between cortical responses to single thalamic spikes and to bursts. We report that bursts enhanced the responses of excitatory neurons and of inhibitory interneurons that preferentially target dendrites. A potential consequence is that bursts will enhance the response to the immediate sensory event over responses to less urgent, modulatory inputs.
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30
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Pluta SR, Lyall EH, Telian GI, Ryapolova-Webb E, Adesnik H. Surround Integration Organizes a Spatial Map during Active Sensation. Neuron 2017; 94:1220-1233.e5. [PMID: 28504117 DOI: 10.1016/j.neuron.2017.04.026] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2016] [Revised: 03/05/2017] [Accepted: 04/18/2017] [Indexed: 01/09/2023]
Abstract
During active sensation, sensors scan space in order to generate a representation of the outside world. However, since spatial coding in sensory systems is typically addressed by measuring receptive fields in a fixed, sensor-based coordinate frame, the cortical representation of scanned space is poorly understood. To address this question, we probed spatial coding in the rodent whisker system using a combination of two-photon imaging and electrophysiology during active touch. We found that surround whiskers powerfully transform the cortical representation of scanned space. On the single-neuron level, surround input profoundly alters response amplitude and modulates spatial preference in the cortex. On the population level, surround input organizes the spatial preference of neurons into a continuous map of the space swept out by the whiskers. These data demonstrate how spatial summation over a moving sensor array is critical to generating population codes of sensory space.
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Affiliation(s)
- Scott R Pluta
- Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
| | - Evan H Lyall
- Biophysics Graduate Group, University of California, Berkeley, Berkeley, CA 94720, USA
| | - Greg I Telian
- Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA
| | - Elena Ryapolova-Webb
- Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA
| | - Hillel Adesnik
- Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
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31
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Endocannabinoid signaling and memory dynamics: A synaptic perspective. Neurobiol Learn Mem 2017; 138:62-77. [DOI: 10.1016/j.nlm.2016.07.031] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2016] [Revised: 07/21/2016] [Accepted: 07/29/2016] [Indexed: 01/26/2023]
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Abstract
Adaptation is fundamental to life. All organisms adapt over timescales that span from evolution to generations and lifetimes to moment-by-moment interactions. The nervous system is particularly adept at rapidly adapting to change, and this in fact may be one of its fundamental principles of organization and function. Rapid forms of sensory adaptation have been well documented across all sensory modalities in a wide range of organisms, yet we do not have a comprehensive understanding of the adaptive cellular mechanisms that ultimately give rise to the corresponding percepts, due in part to the complexity of the circuitry. In this Perspective, we aim to build links between adaptation at multiple scales of neural circuitry by investigating the differential adaptation across brain regions and sub-regions and across specific cell types, for which the explosion of modern tools has just begun to enable. This investigation points to a set of challenges for the field to link functional observations to adaptive properties of the neural circuit that ultimately underlie percepts.
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Affiliation(s)
- Clarissa J Whitmire
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA
| | - Garrett B Stanley
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.
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33
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Bruyns-Haylett M, Luo J, Kennerley AJ, Harris S, Boorman L, Milne E, Vautrelle N, Hayashi Y, Whalley BJ, Jones M, Berwick J, Riera J, Zheng Y. The neurogenesis of P1 and N1: A concurrent EEG/LFP study. Neuroimage 2016; 146:575-588. [PMID: 27646129 PMCID: PMC5312787 DOI: 10.1016/j.neuroimage.2016.09.034] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2016] [Revised: 08/19/2016] [Accepted: 09/15/2016] [Indexed: 10/29/2022] Open
Abstract
It is generally recognised that event related potentials (ERPs) of electroencephalogram (EEG) primarily reflect summed post-synaptic activity of the local pyramidal neural population(s). However, it is still not understood how the positive and negative deflections (e.g. P1, N1 etc) observed in ERP recordings are related to the underlying excitatory and inhibitory post-synaptic activity. We investigated the neurogenesis of P1 and N1 in ERPs by pharmacologically manipulating inhibitory post-synaptic activity in the somatosensory cortex of rodent, and concurrently recording EEG and local field potentials (LFPs). We found that the P1 wave in the ERP and LFP of the supragranular layers is determined solely by the excitatory post-synaptic activity of the local pyramidal neural population, as is the initial segment of the N1 wave across cortical depth. The later part of the N1 wave was modulated by inhibitory post-synaptic activity, with its peak and the pulse width increasing as inhibition was reduced. These findings suggest that the temporal delay of inhibition with respect to excitation observed in intracellular recordings is also reflected in extracellular field potentials (FPs), resulting in a temporal window during which only excitatory post-synaptic activity and leak channel activity are recorded in the ERP and evoked LFP time series. Based on these findings, we provide clarification on the interpretation of P1 and N1 in terms of the excitatory and inhibitory post-synaptic activities of the local pyramidal neural population(s).
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Affiliation(s)
- Michael Bruyns-Haylett
- School of Systems Engineering, Whiteknights, University of Reading, Reading RG6 7AY, United Kingdom.
| | - Jingjing Luo
- School of Systems Engineering, Whiteknights, University of Reading, Reading RG6 7AY, United Kingdom.
| | - Aneurin J Kennerley
- Department of Psychology, University of Sheffield, Sheffield S10 2TP, United Kingdom
| | - Sam Harris
- Department of Psychology, University of Sheffield, Sheffield S10 2TP, United Kingdom
| | - Luke Boorman
- Department of Psychology, University of Sheffield, Sheffield S10 2TP, United Kingdom
| | - Elizabeth Milne
- Department of Psychology, University of Sheffield, Sheffield S10 2TP, United Kingdom
| | - Nicolas Vautrelle
- Department of Psychology, University of Sheffield, Sheffield S10 2TP, United Kingdom
| | - Yurie Hayashi
- School of Systems Engineering, Whiteknights, University of Reading, Reading RG6 7AY, United Kingdom
| | - Benjamin J Whalley
- School of Systems Engineering, Whiteknights, University of Reading, Reading RG6 7AY, United Kingdom
| | - Myles Jones
- Department of Psychology, University of Sheffield, Sheffield S10 2TP, United Kingdom
| | - Jason Berwick
- Department of Psychology, University of Sheffield, Sheffield S10 2TP, United Kingdom
| | - Jorge Riera
- Department of Biomedical Engineering, Florida International University, Miami, FL 33174, United States of America
| | - Ying Zheng
- School of Systems Engineering, Whiteknights, University of Reading, Reading RG6 7AY, United Kingdom.
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Arena A, Lamanna J, Gemma M, Ripamonti M, Ravasio G, Zimarino V, De Vitis A, Beretta L, Malgaroli A. Linear transformation of the encoding mechanism for light intensity underlies the paradoxical enhancement of cortical visual responses by sevoflurane. J Physiol 2016; 595:321-339. [PMID: 27416731 DOI: 10.1113/jp272215] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Accepted: 06/30/2016] [Indexed: 11/08/2022] Open
Abstract
KEY POINTS The mechanisms of action of anaesthetics on the living brain are still poorly understood. In this respect, the analysis of the differential effects of anaesthetics on spontaneous and sensory-evoked cortical activity might provide important and novel cues. Here we show that the anaesthetic sevoflurane strongly silences the brain but potentiates in a dose- and frequency-dependent manner the cortical visual response. Such enhancement arises from a linear scaling by sevoflurane of the power-law relation between light intensity and the cortical response. The fingerprint of sevoflurane action suggests that circuit silencing can boost linearly synaptic responsiveness presumably by scaling the number of responding units and/or their correlation following a sensory stimulation. ABSTRACT General anaesthetics, which are expected to silence brain activity, often spare sensory responses. To evaluate differential effects of anaesthetics on spontaneous and sensory-evoked cortical activity, we characterized their modulation by sevoflurane and propofol. Power spectra and the bust-suppression ratio from EEG data were used to evaluate anaesthesia depth. ON and OFF cortical responses were elicited by light pulses of variable intensity, duration and frequency, during light and deep states of anaesthesia. Both anaesthetics reduced spontaneous cortical activity but sevoflurane greatly enhanced while propofol diminished the ON visual response. Interestingly, the large potentiation of the ON visual response by sevoflurane was found to represent a linear scaling of the encoding mechanism for light intensity. To the contrary, the OFF cortical visual response was depressed by both anaesthetics. The selective depression of the OFF component by sevoflurane could be converted into a robust potentiation by the pharmacological blockade of the ON pathway, suggesting that the temporal order of ON and OFF responses leads to a depression of the latter. This hypothesis agrees with the finding that the enhancement of the ON response was converted into a depression by increasing the frequency of light-pulse stimulation from 0.1 to 1 Hz. Overall, our results support the view that inactivity-dependent modulation of cortical circuits produces an increase in their responsiveness. Among the implications of our findings, the silencing of cortical circuits can boost linearly the cortical responsiveness but with negative impact on their frequency transfer and with a loss of the information content of the sensory signal.
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Affiliation(s)
- Alessandro Arena
- Università Vita-Salute San Raffaele, Milan, Italy.,Neurobiology of Learning Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy
| | - Jacopo Lamanna
- Università Vita-Salute San Raffaele, Milan, Italy.,Neurobiology of Learning Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy
| | - Marco Gemma
- Department of Neuro-anaesthesia and Neuro-intensive Care, Ospedale San Raffaele, Milan, Italy
| | - Maddalena Ripamonti
- Università Vita-Salute San Raffaele, Milan, Italy.,Neurobiology of Learning Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy
| | - Giuliano Ravasio
- Department of Veterinary Science and Public Health, Università degli Studi di Milano, Milan, Italy
| | - Vincenzo Zimarino
- Università Vita-Salute San Raffaele, Milan, Italy.,Neurobiology of Learning Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy
| | - Assunta De Vitis
- Department of Neuro-anaesthesia and Neuro-intensive Care, Ospedale San Raffaele, Milan, Italy
| | - Luigi Beretta
- Department of Neuro-anaesthesia and Neuro-intensive Care, Ospedale San Raffaele, Milan, Italy
| | - Antonio Malgaroli
- Università Vita-Salute San Raffaele, Milan, Italy.,Neurobiology of Learning Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy
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35
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Kremkow J, Perrinet LU, Monier C, Alonso JM, Aertsen A, Frégnac Y, Masson GS. Push-Pull Receptive Field Organization and Synaptic Depression: Mechanisms for Reliably Encoding Naturalistic Stimuli in V1. Front Neural Circuits 2016; 10:37. [PMID: 27242445 PMCID: PMC4862982 DOI: 10.3389/fncir.2016.00037] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2016] [Accepted: 04/25/2016] [Indexed: 11/13/2022] Open
Abstract
Neurons in the primary visual cortex are known for responding vigorously but with high variability to classical stimuli such as drifting bars or gratings. By contrast, natural scenes are encoded more efficiently by sparse and temporal precise spiking responses. We used a conductance-based model of the visual system in higher mammals to investigate how two specific features of the thalamo-cortical pathway, namely push-pull receptive field organization and fast synaptic depression, can contribute to this contextual reshaping of V1 responses. By comparing cortical dynamics evoked respectively by natural vs. artificial stimuli in a comprehensive parametric space analysis, we demonstrate that the reliability and sparseness of the spiking responses during natural vision is not a mere consequence of the increased bandwidth in the sensory input spectrum. Rather, it results from the combined impacts of fast synaptic depression and push-pull inhibition, the later acting for natural scenes as a form of “effective” feed-forward inhibition as demonstrated in other sensory systems. Thus, the combination of feedforward-like inhibition with fast thalamo-cortical synaptic depression by simple cells receiving a direct structured input from thalamus composes a generic computational mechanism for generating a sparse and reliable encoding of natural sensory events.
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Affiliation(s)
- Jens Kremkow
- Institut de Neurosciences de la Timone, UMR 7289, Centre National de la Recherche Scientifique - Aix-Marseille UniversitéMarseille, France; Neurobiology and Biophysics, Faculty of Biology, University of FreiburgFreiburg, Germany; Bernstein Center Freiburg, University of FreiburgFreiburg, Germany; Department of Biological Sciences, State University of New York (SUNY-Optometry)New York, NY, USA
| | - Laurent U Perrinet
- Institut de Neurosciences de la Timone, UMR 7289, Centre National de la Recherche Scientifique - Aix-Marseille Université Marseille, France
| | - Cyril Monier
- Unité de Neurosciences, Information et Complexité, UPR Centre National de la Recherche Scientifique 3293 Gif-sur-Yvette, France
| | - Jose-Manuel Alonso
- Department of Biological Sciences, State University of New York (SUNY-Optometry) New York, NY, USA
| | - Ad Aertsen
- Neurobiology and Biophysics, Faculty of Biology, University of FreiburgFreiburg, Germany; Bernstein Center Freiburg, University of FreiburgFreiburg, Germany
| | - Yves Frégnac
- Unité de Neurosciences, Information et Complexité, UPR Centre National de la Recherche Scientifique 3293 Gif-sur-Yvette, France
| | - Guillaume S Masson
- Institut de Neurosciences de la Timone, UMR 7289, Centre National de la Recherche Scientifique - Aix-Marseille Université Marseille, France
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36
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Fazlali Z, Ranjbar-Slamloo Y, Adibi M, Arabzadeh E. Correlation between Cortical State and Locus Coeruleus Activity: Implications for Sensory Coding in Rat Barrel Cortex. Front Neural Circuits 2016; 10:14. [PMID: 27047339 PMCID: PMC4805600 DOI: 10.3389/fncir.2016.00014] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2015] [Accepted: 03/04/2016] [Indexed: 11/17/2022] Open
Abstract
Cortical state modulates the background activity of cortical neurons, and their evoked response to sensory stimulation. Multiple mechanisms are involved in switching between cortical states including various neuromodulatory systems. Locus Coeruleus (LC) is one of the major neuromodulatory nuclei in the brainstem with widespread projections throughout the brain and modulates the activity of cells and networks. Here, we quantified the link between the LC spontaneous activity, cortical state and sensory processing in the rat vibrissal somatosensory "barrel" cortex (BC). We simultaneously recorded unit activity from LC and BC along with prefrontal electroencephalogram (EEG) while presenting brief whisker deflections under urethane anesthesia. The ratio of low to high frequency components of EEG (referred to as the L/H ratio) was employed to identify cortical state. We found that the spontaneous activity of LC units exhibited a negative correlation with the L/H ratio. Cross-correlation analysis revealed that changes in LC firing preceded changes in the cortical state: the correlation of the LC firing profile with the L/H ratio was maximal at an average lag of -1.2 s. We further quantified BC neuronal responses to whisker stimulation during the synchronized and desynchronized states. In the desynchronized state, BC neurons showed lower stimulus detection threshold, higher response fidelity, and shorter response latency. The most prominent change was observed in the late phase of BC evoked activity (100-400 ms post stimulus onset): almost every BC unit exhibited a greater late response during the desynchronized state. Categorization of the BC evoked responses based on LC activity (into high and low LC discharge rates) resulted in highly similar response profiles compared to categorization based on the cortical state (low and high L/H ratios). These findings provide evidence for the involvement of the LC neuromodulatory system in desynchronization of cortical state and the consequent enhancement of sensory coding efficiency.
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Affiliation(s)
- Zeinab Fazlali
- School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM)Tehran, Iran
- Eccles Institute of Neuroscience, John Curtin School of Medical Research, The Australian National UniversityCanberra, ACT, Australia
- Australian Research Council Centre of Excellence for Integrative Brain Function, The Australian National University NodeCanberra, ACT, Australia
| | - Yadollah Ranjbar-Slamloo
- School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM)Tehran, Iran
- Eccles Institute of Neuroscience, John Curtin School of Medical Research, The Australian National UniversityCanberra, ACT, Australia
- Australian Research Council Centre of Excellence for Integrative Brain Function, The Australian National University NodeCanberra, ACT, Australia
| | - Mehdi Adibi
- Eccles Institute of Neuroscience, John Curtin School of Medical Research, The Australian National UniversityCanberra, ACT, Australia
- Australian Research Council Centre of Excellence for Integrative Brain Function, The Australian National University NodeCanberra, ACT, Australia
| | - Ehsan Arabzadeh
- Eccles Institute of Neuroscience, John Curtin School of Medical Research, The Australian National UniversityCanberra, ACT, Australia
- Australian Research Council Centre of Excellence for Integrative Brain Function, The Australian National University NodeCanberra, ACT, Australia
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37
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Ferrati G, Martini FJ, Maravall M. Presynaptic Adenosine Receptor-Mediated Regulation of Diverse Thalamocortical Short-Term Plasticity in the Mouse Whisker Pathway. Front Neural Circuits 2016; 10:9. [PMID: 26941610 PMCID: PMC4763074 DOI: 10.3389/fncir.2016.00009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2015] [Accepted: 02/05/2016] [Indexed: 12/27/2022] Open
Abstract
Short-term synaptic plasticity (STP) sets the sensitivity of a synapse to incoming activity and determines the temporal patterns that it best transmits. In “driver” thalamocortical (TC) synaptic populations, STP is dominated by depression during stimulation from rest. However, during ongoing stimulation, lemniscal TC connections onto layer 4 neurons in mouse barrel cortex express variable STP. Each synapse responds to input trains with a distinct pattern of depression or facilitation around its mean steady-state response. As a result, in common with other synaptic populations, lemniscal TC synapses express diverse rather than uniform dynamics, allowing for a rich representation of temporally varying stimuli. Here, we show that this STP diversity is regulated presynaptically. Presynaptic adenosine receptors of the A1R type, but not kainate receptors (KARs), modulate STP behavior. Blocking the receptors does not eliminate diversity, indicating that diversity is related to heterogeneous expression of multiple mechanisms in the pathway from presynaptic calcium influx to neurotransmitter release.
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Affiliation(s)
- Giovanni Ferrati
- Instituto de Neurociencias de Alicante UMH-CSIC Sant Joan d'Alacant, Spain
| | | | - Miguel Maravall
- Instituto de Neurociencias de Alicante UMH-CSICSant Joan d'Alacant, Spain; School of Life Sciences, Sussex Neuroscience, University of SussexBrighton, UK
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38
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39
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Distinct recurrent versus afferent dynamics in cortical visual processing. Nat Neurosci 2015; 18:1789-97. [PMID: 26502263 DOI: 10.1038/nn.4153] [Citation(s) in RCA: 120] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Accepted: 09/30/2015] [Indexed: 01/21/2023]
Abstract
How intracortical recurrent circuits in mammalian sensory cortex influence dynamics of sensory representation is not understood. Previous methods could not distinguish the relative contributions of recurrent circuits and thalamic afferents to cortical dynamics. We accomplish this by optogenetically manipulating thalamus and cortex. Over the initial 40 ms of visual stimulation, excitation from recurrent circuits in visual cortex progressively increased to exceed direct thalamocortical excitation. Even when recurrent excitation exceeded thalamic excitation, upon silencing thalamus, sensory-evoked activity in cortex decayed rapidly, with a time constant of 10 ms, which is similar to a neuron's integration time window. In awake mice, this cortical decay function predicted the time-locking of cortical activity to thalamic input at frequencies <15 Hz and attenuation of the cortical response to higher frequencies. Under anesthesia, depression at thalamocortical synapses disrupted the fidelity of sensory transmission. Thus, we determine dynamics intrinsic to cortical recurrent circuits that transform afferent input in time.
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40
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Stoelzel CR, Huff JM, Bereshpolova Y, Zhuang J, Hei X, Alonso JM, Swadlow HA. Hour-long adaptation in the awake early visual system. J Neurophysiol 2015; 114:1172-82. [PMID: 26108950 DOI: 10.1152/jn.00116.2015] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2015] [Accepted: 06/16/2015] [Indexed: 12/30/2022] Open
Abstract
Sensory adaptation serves to adjust awake brains to changing environments on different time scales. However, adaptation has been studied traditionally under anesthesia and for short time periods. Here, we demonstrate in awake rabbits a novel type of sensory adaptation that persists for >1 h and acts on visual thalamocortical neurons and their synapses in the input layers of the visual cortex. Following prolonged visual stimulation (10-30 min), cells in the dorsal lateral geniculate nucleus (LGN) show a severe and prolonged reduction in spontaneous firing rate. This effect is bidirectional, and prolonged visually induced response suppression is followed by a prolonged increase in spontaneous activity. The reduction in thalamic spontaneous activity following prolonged visual activation is accompanied by increases in 1) response reliability, 2) signal detectability, and 3) the ratio of visual signal/spontaneous activity. In addition, following such prolonged activation of an LGN neuron, the monosynaptic currents generated by thalamic impulses in layer 4 of the primary visual cortex are enhanced. These results demonstrate that in awake brains, prolonged sensory stimulation can have a profound, long-lasting effect on the information conveyed by thalamocortical inputs to the visual cortex.
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Affiliation(s)
- Carl R Stoelzel
- Department of Psychology, University of Connecticut, Storrs, Connecticut; and
| | - Joseph M Huff
- Department of Psychology, University of Connecticut, Storrs, Connecticut; and
| | - Yulia Bereshpolova
- Department of Psychology, University of Connecticut, Storrs, Connecticut; and
| | - Jun Zhuang
- Department of Psychology, University of Connecticut, Storrs, Connecticut; and
| | - Xiaojuan Hei
- Department of Psychology, University of Connecticut, Storrs, Connecticut; and
| | - Jose-Manuel Alonso
- Department of Psychology, University of Connecticut, Storrs, Connecticut; and Department of Biological Sciences, State University of New York, New York, New York
| | - Harvey A Swadlow
- Department of Psychology, University of Connecticut, Storrs, Connecticut; and Department of Biological Sciences, State University of New York, New York, New York
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41
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Schiemann J, Puggioni P, Dacre J, Pelko M, Domanski A, van Rossum MCW, Duguid I. Cellular mechanisms underlying behavioral state-dependent bidirectional modulation of motor cortex output. Cell Rep 2015; 11:1319-30. [PMID: 25981037 PMCID: PMC4451462 DOI: 10.1016/j.celrep.2015.04.042] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2014] [Revised: 03/16/2015] [Accepted: 04/20/2015] [Indexed: 11/25/2022] Open
Abstract
Neuronal activity in primary motor cortex (M1) correlates with behavioral state, but the cellular mechanisms underpinning behavioral state-dependent modulation of M1 output remain largely unresolved. Here, we performed in vivo patch-clamp recordings from layer 5B (L5B) pyramidal neurons in awake mice during quiet wakefulness and self-paced, voluntary movement. We show that L5B output neurons display bidirectional (i.e., enhanced or suppressed) firing rate changes during movement, mediated via two opposing subthreshold mechanisms: (1) a global decrease in membrane potential variability that reduced L5B firing rates (L5Bsuppressed neurons), and (2) a coincident noradrenaline-mediated increase in excitatory drive to a subpopulation of L5B neurons (L5Benhanced neurons) that elevated firing rates. Blocking noradrenergic receptors in forelimb M1 abolished the bidirectional modulation of M1 output during movement and selectively impaired contralateral forelimb motor coordination. Together, our results provide a mechanism for how noradrenergic neuromodulation and network-driven input changes bidirectionally modulate M1 output during motor behavior.
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Affiliation(s)
- Julia Schiemann
- Centre for Integrative Physiology and Patrick Wild Centre, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK
| | - Paolo Puggioni
- Centre for Integrative Physiology and Patrick Wild Centre, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK; Institute for Adaptive and Neural Computation, School of Informatics, University of Edinburgh, Edinburgh EH8 9AB, UK; Neuroinformatics Doctoral Training Centre, School of Informatics, University of Edinburgh, Edinburgh EH8 9AB, UK
| | - Joshua Dacre
- Centre for Integrative Physiology and Patrick Wild Centre, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK
| | - Miha Pelko
- Institute for Adaptive and Neural Computation, School of Informatics, University of Edinburgh, Edinburgh EH8 9AB, UK; Neuroinformatics Doctoral Training Centre, School of Informatics, University of Edinburgh, Edinburgh EH8 9AB, UK
| | - Aleksander Domanski
- Centre for Integrative Physiology and Patrick Wild Centre, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK
| | - Mark C W van Rossum
- Institute for Adaptive and Neural Computation, School of Informatics, University of Edinburgh, Edinburgh EH8 9AB, UK
| | - Ian Duguid
- Centre for Integrative Physiology and Patrick Wild Centre, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK.
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42
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Sobolewski A, Kublik E, Swiejkowski DA, Kamiński J, Wróbel A. Alertness opens the effective flow of sensory information through rat thalamic posterior nucleus. Eur J Neurosci 2015; 41:1321-31. [DOI: 10.1111/ejn.12901] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2013] [Accepted: 03/18/2015] [Indexed: 02/03/2023]
Affiliation(s)
- Aleksander Sobolewski
- Department of Neurophysiology; Nencki Institute of Experimental Biology; 3 Pasteur Str. Warsaw 02-093 Poland
| | - Ewa Kublik
- Department of Neurophysiology; Nencki Institute of Experimental Biology; 3 Pasteur Str. Warsaw 02-093 Poland
| | - Daniel A. Swiejkowski
- Department of Neurophysiology; Nencki Institute of Experimental Biology; 3 Pasteur Str. Warsaw 02-093 Poland
| | - Jan Kamiński
- Department of Neurophysiology; Nencki Institute of Experimental Biology; 3 Pasteur Str. Warsaw 02-093 Poland
| | - Andrzej Wróbel
- Department of Neurophysiology; Nencki Institute of Experimental Biology; 3 Pasteur Str. Warsaw 02-093 Poland
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43
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Abstract
The cortical network recurrent circuitry generates spontaneous activity organized into Up (active) and Down (quiescent) states during slow-wave sleep or anesthesia. These different states of cortical activation gain modulate synaptic transmission. However, the reported modulation that Up states impose on synaptic inputs is disparate in the literature, including both increases and decreases of responsiveness. Here, we tested the hypothesis that such disparate observations may depend on the intensity of the stimulation. By means of intracellular recordings, we studied synaptic transmission during Up and Down states in rat auditory cortex in vivo. Synaptic potentials were evoked either by auditory or electrical (thalamocortical, intracortical) stimulation while randomly varying the intensity of the stimulus. Synaptic potentials evoked by the same stimulus intensity were compared in Up/Down states. Up states had a scaling effect on the stimulus-evoked synaptic responses: the amplitude of weaker responses was potentiated whereas that of larger responses was maintained or decreased with respect to the amplitude during Down states. We used a computational model to explore the potential mechanisms explaining this nontrivial stimulus-response relationship. During Up/Down states, there is different excitability in the network and the neuronal conductance varies. We demonstrate that the competition between presynaptic recruitment and the changing conductance might be the central mechanism explaining the experimentally observed stimulus-response relationships. We conclude that the effect that cortical network activation has on synaptic transmission is not constant but contingent on the strength of the stimulation, with a larger modulation for stimuli involving both thalamic and cortical networks.
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44
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Castro-Alamancos MA, Bezdudnaya T. Modulation of artificial whisking related signals in barrel cortex. J Neurophysiol 2015; 113:1287-301. [PMID: 25505118 PMCID: PMC4346718 DOI: 10.1152/jn.00809.2014] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2014] [Accepted: 12/08/2014] [Indexed: 11/22/2022] Open
Abstract
Rats use rhythmic whisker movements, called active whisking, to sense the environment, which include whisker protractions followed by retractions at various frequencies. Using a proxy of active whisking in anesthetized rats, called artificial whisking, which is induced by electrically stimulating the facial motor nerve, we characterized the neural responses evoked in the barrel cortex by whisking in air (without contact) and on a surface (with contact). Neural responses were compared between distinct network states consisting of cortical deactivation (synchronized slow oscillations) and activation (desynchronized state) produced by neuromodulation (cholinergic or noradrenergic stimulation in neocortex or thalamus). Here we show that population responses in the barrel cortex consist of a robust signal driven by the onset of the whisker protraction followed by a whisking retraction signal that emerges during low frequency whisking on a surface. The whisking movement onset signal is suppressed by increasing whisking frequency, is controlled by cortical synaptic inhibition, is suppressed during cortical activation states, is little affected by whisking on a surface, and is ubiquitous in ventroposterior medial (VPM) thalamus, barrel cortex, and superior colliculus. The whisking retraction signal codes the duration of the preceding whisker protraction, is present in thalamocortical networks but not in superior colliculus, and is robust during cortical activation; a state associated with natural exploratory whisking. The expression of different whisking signals in forebrain and midbrain may define the sensory processing abilities of those sensorimotor circuits. Whisking related signals in the barrel cortex are controlled by network states that are set by neuromodulators.
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Affiliation(s)
- Manuel A Castro-Alamancos
- Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania
| | - Tatiana Bezdudnaya
- Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania
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45
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Abstract
Neocortical population activity varies between deactivated and activated states marked by the presence and absence of slow oscillations, respectively. Neocortex activation occurs during waking and vigilance and is readily induced in anesthetized animals by stimulating the brainstem reticular formation, basal forebrain, or thalamus. Neuromodulators are thought to be responsible for these changes in cortical activity, but their selective cortical effects (i.e., without actions in other brain areas) on neocortical population activity in vivo are not well defined. We found that selective cholinergic and noradrenergic stimulation of the barrel cortex produces well differentiated activated states in rats. Cholinergic cortical stimulation activates the cortex by abolishing synchronous slow oscillations and shifting firing to a tonic mode, which increases in rate at high doses. This shift causes the sensory thalamus itself to become activated. In contrast, noradrenergic cortical stimulation activates the cortex by abolishing synchronous slow oscillations but suppresses overall cortical firing rate, which deactivates the thalamus. Cortical activation produced by either of these neuromodulators leads to suppressed sensory responses and more focused receptive fields. High-frequency sensory stimuli are best relayed to barrel cortex during cortical cholinergic activation because this also activates the thalamus. Cortical neuromodulation sets different cortical and thalamic states that may serve to control sensory information processing according to behavioral contingencies.
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46
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Zagha E, McCormick DA. Neural control of brain state. Curr Opin Neurobiol 2014; 29:178-86. [PMID: 25310628 DOI: 10.1016/j.conb.2014.09.010] [Citation(s) in RCA: 118] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2014] [Revised: 08/28/2014] [Accepted: 09/13/2014] [Indexed: 11/16/2022]
Abstract
How the brain takes in information, makes a decision, and acts on this decision is strongly influenced by the ongoing and constant fluctuations of state. Understanding the nature of these brain states and how they are controlled is critical to making sense of how the nervous system operates, both normally and abnormally. While broadly projecting neuromodulatory systems acting through metabotropic pathways have long been appreciated to be critical for determining brain state, more recent investigations have revealed a prominent role for fast acting neurotransmitter pathways for temporally and spatially precise control of neural processing. Corticocortical and thalamocortical glutamatergic projections can rapidly and precisely control brain state by changing both the nature of ongoing activity and by controlling the gain and precision of neural responses.
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Affiliation(s)
- Edward Zagha
- Department of Neurobiology, Kavli Institute for Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, United States
| | - David A McCormick
- Department of Neurobiology, Kavli Institute for Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, United States.
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47
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Cimenser A, Miller KD. The effects of short-term synaptic depression at thalamocortical synapses on orientation tuning in cat V1. PLoS One 2014; 9:e106046. [PMID: 25157879 PMCID: PMC4144965 DOI: 10.1371/journal.pone.0106046] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2014] [Accepted: 07/30/2014] [Indexed: 12/02/2022] Open
Abstract
We examine the effects of short-term synaptic depression on the orientation tuning of the LGN input to simple cells in cat primary visual cortex (V1). The total LGN input has an untuned component as well as a tuned component, both of which grow with stimulus contrast. The untuned component is not visible in the firing rate responses of the simple cells. The suppression of the contribution of the untuned input component to firing rate responses is key to establishing orientation selectivity and its invariance with stimulus contrast. It has been argued that synaptic depression of LGN inputs could contribute to the selective suppression of the untuned component and thus contribute to the tuning observed in simple cells. We examine this using a model fit to the depression observed at thalamocortical synapses in-vivo, and compare this to an earlier model fit based on in-vitro observations. We examine the tuning of both the conductance and the firing rate induced in simple cells by the net LGN input. We find that depression causes minimal suppression of the untuned component. The primary effect of depression is to cause the contrast response curve to saturate at lower contrasts without differentially affecting the tuned vs. untuned components. This effect is slightly weaker for in-vivo vs. in-vitro parameters. Thus, synaptic depression of LGN inputs does not appreciably contribute to the orientation tuning of V1 simple cells.
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Affiliation(s)
- Aylin Cimenser
- Harvard Medical School, Boston, Massachusetts, United States of America
- Department of Physics, Boston University, Boston, Massachusetts, United States of America
- * E-mail:
| | - Kenneth D. Miller
- Center for Theoretical Neuroscience, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America
- Department of Neuroscience, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America
- Swartz Program in Theoretical Neuroscience, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America
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48
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Abstract
The superior colliculus is part of a broader neural network that can decode whisker movements in air and on objects, which is a strategy used by behaving rats to sense the environment. The intermediate layers of the superior colliculus receive whisker-related excitatory afferents from the trigeminal complex and barrel cortex, inhibitory afferents from extrinsic and intrinsic sources, and neuromodulatory afferents from cholinergic and monoaminergic nuclei. However, it is not well known how these inputs regulate whisker-related activity in the superior colliculus. We found that barrel cortex afferents drive the superior colliculus during the middle portion of the rising phase of the whisker movement protraction elicited by artificial (fictive) whisking in anesthetized rats. In addition, both spontaneous and whisker-related neural activities in the superior colliculus are under strong inhibitory and neuromodulator control. Cholinergic stimulation activates the superior colliculus by increasing spontaneous firing and, in some cells, whisker-evoked responses. Monoaminergic stimulation has the opposite effects. The actions of neuromodulator and inhibitory afferents may be the basis of the different firing rates and sensory responsiveness observed in the superior colliculus of behaving animals during distinct behavioral states.
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49
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Dynamic circuit motifs underlying rhythmic gain control, gating and integration. Nat Neurosci 2014; 17:1031-9. [DOI: 10.1038/nn.3764] [Citation(s) in RCA: 228] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2014] [Accepted: 06/16/2014] [Indexed: 12/12/2022]
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50
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Abstract
To produce sensation, neuronal pathways must transmit and process stimulus patterns that unfold over time. This behavior is determined by short-term synaptic plasticity (STP), which shapes the temporal filtering properties of synapses in a pathway. We explored STP variability across thalamocortical (TC) synapses, measuring whole-cell responses to stimulation of TC fibers in layer 4 neurons of mouse barrel cortex in vitro. As expected, STP during stimulation from rest was dominated by depression. However, STP during ongoing stimulation was strikingly diverse across TC connections. Diversity took the form of variable tuning to the latest interstimulus interval: some connections responded weakly to shorter intervals, while other connections were facilitated. These behaviors did not cluster into categories but formed a continuum. Diverse tuning did not require disynaptic inhibition. Hence, monosynaptic excitatory lemniscal TC connections onto layer 4 do not behave uniformly during ongoing stimulation. Each connection responds differentially to particular stimulation intervals, enriching the ability of the pathway to convey complex, temporally fluctuating information.
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