|
1
|
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.
Collapse
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
| |
Collapse
|
|
2
|
McLachlan NM, Wilson SJ. The Contribution of Brainstem and Cerebellar Pathways to Auditory Recognition. Front Psychol 2017; 8:265. [PMID: 28373850 PMCID: PMC5357638 DOI: 10.3389/fpsyg.2017.00265] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2016] [Accepted: 02/10/2017] [Indexed: 12/02/2022] Open
Abstract
The cerebellum has been known to play an important role in motor functions for many years. More recently its role has been expanded to include a range of cognitive and sensory-motor processes, and substantial neuroimaging and clinical evidence now points to cerebellar involvement in most auditory processing tasks. In particular, an increase in the size of the cerebellum over recent human evolution has been attributed in part to the development of speech. Despite this, the auditory cognition literature has largely overlooked afferent auditory connections to the cerebellum that have been implicated in acoustically conditioned reflexes in animals, and could subserve speech and other auditory processing in humans. This review expands our understanding of auditory processing by incorporating cerebellar pathways into the anatomy and functions of the human auditory system. We reason that plasticity in the cerebellar pathways underpins implicit learning of spectrotemporal information necessary for sound and speech recognition. Once learnt, this information automatically recognizes incoming auditory signals and predicts likely subsequent information based on previous experience. Since sound recognition processes involving the brainstem and cerebellum initiate early in auditory processing, learnt information stored in cerebellar memory templates could then support a range of auditory processing functions such as streaming, habituation, the integration of auditory feature information such as pitch, and the recognition of vocal communications.
Collapse
Affiliation(s)
- Neil M. McLachlan
- Melbourne School of Psychological Sciences, University of MelbourneMelbourne, VIC, Australia
| | | |
Collapse
|
|
3
|
Petzold A, Valencia M, Pál B, Mena-Segovia J. Decoding brain state transitions in the pedunculopontine nucleus: cooperative phasic and tonic mechanisms. Front Neural Circuits 2015; 9:68. [PMID: 26582977 PMCID: PMC4628121 DOI: 10.3389/fncir.2015.00068] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2015] [Accepted: 10/15/2015] [Indexed: 02/03/2023] Open
Abstract
Cholinergic neurons of the pedunculopontine nucleus (PPN) are most active during the waking state. Their activation is deemed to cause a switch in the global brain activity from sleep to wakefulness, while their sustained discharge may contribute to upholding the waking state and enhancing arousal. Similarly, non-cholinergic PPN neurons are responsive to brain state transitions and their activation may influence some of the same targets of cholinergic neurons, suggesting that they operate in coordination. Yet, it is not clear how the discharge of distinct classes of PPN neurons organize during brain states. Here, we monitored the in vivo network activity of PPN neurons in the anesthetized rat across two distinct levels of cortical dynamics and their transitions. We identified a highly structured configuration in PPN network activity during slow-wave activity that was replaced by decorrelated activity during the activated state (AS). During the transition, neurons were predominantly excited (phasically or tonically), but some were inhibited. Identified cholinergic neurons displayed phasic and short latency responses to sensory stimulation, whereas the majority of non-cholinergic showed tonic responses and remained at high discharge rates beyond the state transition. In vitro recordings demonstrate that cholinergic neurons exhibit fast adaptation that prevents them from discharging at high rates over prolonged time periods. Our data shows that PPN neurons have distinct but complementary roles during brain state transitions, where cholinergic neurons provide a fast and transient response to sensory events that drive state transitions, whereas non-cholinergic neurons maintain an elevated firing rate during global activation.
Collapse
Affiliation(s)
- Anne Petzold
- MRC Anatomical Neuropharmacology Unit, Department of Pharmacology, University of Oxford Oxford, UK
| | - Miguel Valencia
- Neurosciences Area, CIMA, Universidad de Navarra Pamplona, Spain ; IdiSNA, Navarra Institute for Health Research Pamplona, Spain
| | - Balázs Pál
- Department of Physiology, Faculty of Medicine University of Debrecen Debrecen, Hungary
| | - Juan Mena-Segovia
- MRC Anatomical Neuropharmacology Unit, Department of Pharmacology, University of Oxford Oxford, UK ; Center for Molecular and Behavioral Neuroscience, Rutgers University Newark, NJ, USA
| |
Collapse
|
|
4
|
Tsanov M, O'Mara SM. Decoding signal processing in thalamo-hippocampal circuitry: implications for theories of memory and spatial processing. Brain Res 2014; 1621:368-79. [PMID: 25498107 DOI: 10.1016/j.brainres.2014.12.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Revised: 11/30/2014] [Accepted: 12/01/2014] [Indexed: 10/24/2022]
Abstract
A major tool in understanding how information is processed in the brain is the analysis of neuronal output at each hierarchical level through which neurophysiological signals are propagated. Since the experimental brain operation performed on Henry Gustav Molaison (known as patient H.M.) in 1953, the hippocampal formation has gained special attention, resulting in a very large number of studies investigating signals processed by the hippocampal formation. One of the main information streams to the hippocampal formation, vital for episodic memory formation, arises from thalamo-hippocampal projections, as there is extensive connectivity between these structures. This connectivity is sometimes overlooked by theories of memory formation by the brain, in favour of theories with a strong cortico-hippocampal flavour. In this review, we attempt to address some of the complexity of the signals processed within the thalamo-hippocampal circuitry. To understand the signals encoded by the anterior thalamic nuclei in particular, we review key findings from electrophysiological, anatomical, behavioural and computational studies. We include recent findings elucidating the integration of different signal modalities by single thalamic neurons; we focus in particular on the propagation of two prominent signals: head directionality and theta rhythm. We conclude that thalamo-hippocampal processing provides a centrally important, substantive, and dynamic input modulating and moderating hippocampal spatial and mnemonic processing. This article is part of a Special Issue entitled SI: Brain and Memory.
Collapse
Affiliation(s)
- Marian Tsanov
- Trinity College Institute of Neuroscience, Trinity College Dublin, Ireland; School of Psychology, Trinity College Dublin, Ireland
| | - Shane M O'Mara
- Trinity College Institute of Neuroscience, Trinity College Dublin, Ireland; School of Psychology, Trinity College Dublin, Ireland.
| |
Collapse
|
|
5
|
Tsanov M, Chah E, Noor MS, Egan C, Reilly RB, Aggleton JP, Erichsen JT, Vann SD, O'Mara SM. The irregular firing properties of thalamic head direction cells mediate turn-specific modulation of the directional tuning curve. J Neurophysiol 2014; 112:2316-31. [PMID: 25122712 PMCID: PMC4274931 DOI: 10.1152/jn.00583.2013] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Head direction cells encode an animal's heading in the horizontal plane. However, it is not clear
why the directionality of a cell's mean firing rate differs for clockwise, compared with
counterclockwise, head turns (this difference is known as the “separation angle”) in
anterior thalamus. Here we investigated in freely behaving rats whether intrinsic neuronal firing
properties are linked to this phenomenon. We found a positive correlation between the separation
angle and the spiking variability of thalamic head direction cells. To test whether this link is
driven by hyperpolarization-inducing currents, we investigated the effect of thalamic reticular
inhibition during high-voltage spindles on directional spiking. While the selective directional
firing of thalamic neurons was preserved, we found no evidence for entrainment of thalamic head
direction cells by high-voltage spindle oscillations. We then examined the role of
depolarization-inducing currents in the formation of separation angle. Using a single-compartment
Hodgkin-Huxley model, we show that modeled neurons fire with higher frequencies during the ascending
phase of sinusoidal current injection (mimicking the head direction tuning curve) when simulated
with higher high-threshold calcium channel conductance. These findings demonstrate that the
turn-specific encoding of directional signal strongly depends on the ability of thalamic neurons to
fire irregularly in response to sinusoidal excitatory activation. Another crucial factor for
inducing phase lead to sinusoidal current injection was the presence of spike-frequency adaptation
current in the modeled neurons. Our data support a model in which intrinsic biophysical properties
of thalamic neurons mediate the physiological encoding of directional information.
Collapse
Affiliation(s)
- Marian Tsanov
- Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland; School of Psychology, Trinity College Dublin, Dublin, Ireland
| | - Ehsan Chah
- Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland; Trinity Centre for Bioengineering, Trinity College Dublin, Dublin, Ireland
| | - Muhammad S Noor
- Trinity Centre for Bioengineering, Trinity College Dublin, Dublin, Ireland
| | - Catriona Egan
- Trinity Centre for Bioengineering, Trinity College Dublin, Dublin, Ireland
| | - Richard B Reilly
- Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland; Trinity Centre for Bioengineering, Trinity College Dublin, Dublin, Ireland
| | - John P Aggleton
- School of Psychology, Cardiff University, Cardiff, United Kingdom; and
| | - Jonathan T Erichsen
- School of Optometry and Vision Sciences, Cardiff University, Cardiff, United Kingdom
| | - Seralynne D Vann
- School of Psychology, Cardiff University, Cardiff, United Kingdom; and
| | - Shane M O'Mara
- Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland; School of Psychology, Trinity College Dublin, Dublin, Ireland;
| |
Collapse
|
|
6
|
Kulkarni M, Zhang K, Kirkwood A. Single-cell persistent activity in anterodorsal thalamus. Neurosci Lett 2011; 498:179-84. [PMID: 21362457 PMCID: PMC3117030 DOI: 10.1016/j.neulet.2011.02.051] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2010] [Revised: 02/14/2011] [Accepted: 02/22/2011] [Indexed: 10/18/2022]
Abstract
The anterodorsal nucleus of the thalamus contains a high percentage of head-direction cells whose activities are correlated with an animal's directional heading in the horizontal plane. The firing of head-direction cells could involve self-sustaining reverberating activity in a recurrent network, but the thalamus by itself lacks strong excitatory recurrent synaptic connections to sustain tonic reverberating activity. Here we examined whether a single thalamic neuron could sustain its own activity without synaptic input by recording from individual neurons from anterodorsal thalamus in brain slices with synaptic blockers. We found that the rebound firing induced by hyperpolarizing pulses often decayed slowly so that a thalamic neuron could keep on firing for many minutes after stimulation. The hyperpolarization-induced persistent firing rate was graded under repeated current injections, and could be enhanced by serotonin. The effect of depolarizing pulses was much weaker and only slightly accelerated the decay of the hyperpolarization-induced persistent firing. Our finding provides the first direct evidence for single-cell persistent activity in the thalamus, supporting the notion that cellular mechanisms at the slow time scale of minutes might potentially contribute to the operations of the head-direction system.
Collapse
Affiliation(s)
- Mauktik Kulkarni
- Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21218, United States
| | | | | |
Collapse
|
|
7
|
Aggleton JP, O'Mara SM, Vann SD, Wright NF, Tsanov M, Erichsen JT. Hippocampal-anterior thalamic pathways for memory: uncovering a network of direct and indirect actions. Eur J Neurosci 2010; 31:2292-307. [PMID: 20550571 PMCID: PMC2936113 DOI: 10.1111/j.1460-9568.2010.07251.x] [Citation(s) in RCA: 333] [Impact Index Per Article: 22.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
This review charts recent advances from a variety of disciplines that create a new perspective on why the multiple hippocampal–anterior thalamic interconnections are together vital for human episodic memory and rodent event memory. Evidence has emerged for the existence of a series of parallel temporal–diencephalic pathways that function in a reciprocal manner, both directly and indirectly, between the hippocampal formation and the anterior thalamic nuclei. These extended pathways also involve the mammillary bodies, the retrosplenial cortex and parts of the prefrontal cortex. Recent neuropsychological findings reveal the disproportionate importance of these hippocampal–anterior thalamic systems for recollective rather than familiarity-based recognition, while anatomical studies highlight the precise manner in which information streams are kept separate but can also converge at key points within these pathways. These latter findings are developed further by electrophysiological stimulation studies showing how the properties of the direct hippocampal–anterior thalamic projections are often opposed by the indirect hippocampal projections via the mammillary bodies to the thalamus. Just as these hippocampal–anterior thalamic interactions reflect an interdependent system, so it is also the case that pathology in one of the component sites within this system can induce dysfunctional changes to distal sites both directly and indirectly across the system. Such distal effects challenge more traditional views of neuropathology as they reveal how extensive covert pathology might accompany localised overt pathology, and so impair memory.
Collapse
Affiliation(s)
- John P Aggleton
- School of Psychology, Cardiff University, Tower Building, Park Place, Cardiff, Wales CF10 3AT, UK.
| | | | | | | | | | | |
Collapse
|
|
8
|
Oda S, Sato F, Okada A, Akahane S, Igarashi H, Yokofujita J, Yang J, Kuroda M. Immunolocalization of muscarinic receptor subtypes in the reticular thalamic nucleus of rats. Brain Res Bull 2007; 74:376-84. [PMID: 17845913 DOI: 10.1016/j.brainresbull.2007.07.017] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2006] [Revised: 04/24/2007] [Accepted: 07/05/2007] [Indexed: 11/29/2022]
Abstract
In this study, to identify the precise localization of the muscarinic receptor subtypes m2, m3 and m4 in the rostral part of the rat reticular thalamic nucleus (rRt), namely, the limbic sector, we used receptor-subtype-specific antibodies and characterized the immunolabeled structures by light, confocal laser scanning, and electron microscopies. The m2-immunolabeling was preferentially distributed in the distal dendrite region where cholinergic afferent fibers tend to terminate and in the peripheral region of somata, whereas the m3-immunolabeling was more preferentially distributed in a large part of somata and in proximal dendrite shafts than in the distal dendrite region. Dual-immunofluorescence experiments demonstrated that majority of rRt neurons with parvalbumin immunoreactivity contain both m2 and m3. Neither m2 nor m3 was detected in presynaptic terminals or axonal elements. No m4-immunolabeling was detected in the rostral part of the thalamus including rRt. These results show the different distributions of m2 and m3 in rRt neurons, and strongly suggest that m2 is more closely associated with cholinergic afferents than m3.
Collapse
Affiliation(s)
- Satoko Oda
- Department of Anatomy, Toho University School of Medicine, Tokyo, Japan.
| | | | | | | | | | | | | | | |
Collapse
|
|
9
|
Trageser JC, Burke KA, Masri R, Li Y, Sellers L, Keller A. State-dependent gating of sensory inputs by zona incerta. J Neurophysiol 2006; 96:1456-63. [PMID: 16775205 PMCID: PMC1764852 DOI: 10.1152/jn.00423.2006] [Citation(s) in RCA: 80] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
We have previously shown that the GABAergic nucleus zona incerta (ZI) suppresses vibrissae-evoked responses in the posterior medial (POm) thalamus of the rodent somatosensory system. We proposed that this inhibitory incerto-thalamic pathway regulates POm responses during different behavioral states. Here we tested the hypothesis that the cholinergic reticular activating system, implicated in regulating states of arousal, modulates ZI activity. We show that stimulation of brain stem cholinergic nuclei (laterodorsal tegmental and pedunculopontine tegmental) results in suppression of spontaneous firing of ZI neurons. Iontophoretic application of the cholinergic agonist carbachol to ZI neurons suppresses both their spontaneous firing and their vibrissae-evoked responses. We also found that carbachol application to an in vitro slice preparation suppresses spontaneous firing of neurons in the ventral sector of ZI (ZIv). Finally, we demonstrate that the majority of ZIv neurons contain parvalbumin and project to POm. Based on these results, we present the state-dependent gating hypothesis, which states that differing behavioral states-regulated by the brain stem cholinergic system-modulate ZI activity, thereby regulating the response properties of higher-order nuclei such as POm.
Collapse
Affiliation(s)
| | | | | | | | | | - Asaf Keller
- Address for reprint requests and other correspondence: A. Keller, Dept. of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn St., Baltimore, MD 21201 (E-mail: )
| |
Collapse
|
|
10
|
Endoh T. Modulation of voltage-dependent calcium channels by neurotransmitters and neuropeptides in parasympathetic submandibular ganglion neurons. Arch Oral Biol 2004; 49:539-57. [PMID: 15126136 DOI: 10.1016/j.archoralbio.2004.02.005] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/03/2004] [Indexed: 12/20/2022]
Abstract
The control of saliva secretion is mainly under parasympathetic control, although there also could be a sympathetic component. Sympathetic nerves are held to have a limited action in secretion in submandibular glands because, on electrical stimulation, only a very small increase to the normal background, basal secretion occurs. Parasympathetic stimulation, on the other hand, caused a good flow of saliva with moderate secretion of acinar mucin, plus an extensive secretion of granules from the granular tubules. The submandibular ganglion (SMG) is a parasympathetic ganglion which receives inputs from preganglionic cholinergic neurons, and innervates the submandibular salivary gland to control saliva secretion. Neurotransmitters and neuropeptides acting via G-protein coupled receptors (GPCRs) change the electrical excitability of neurons. In these neurons, many neurotransmitters and neuropeptides modulate voltage-dependent calcium channels (VDCCs). The modulation is mediated by a family of GPCRs acting either directly through the membrane delimited G-proteins or through second messengers. However, the mechanism of modulation and the signal transduction pathway linked to an individual GPCRs depend on the animal species. This review reports how neurotransmitters and neuropeptides modulate VDCCs and how these modulatory actions are integrated in SMG systems. The action of neurotransmitters and neuropeptides on VDCCs may provide a mechanism for regulating SMG excitability and also provide a cellular mechanism of a variety of neuronal Ca(2+)-dependent processes.
Collapse
Affiliation(s)
- Takayuki Endoh
- Department of Physiology, Tokyo Dental College, 1-2-2 Masago, Mihama-ku, Chiba 261-8502, Japan.
| |
Collapse
|
|
11
|
Hasselmo ME, McGaughy J. High acetylcholine levels set circuit dynamics for attention and encoding and low acetylcholine levels set dynamics for consolidation. PROGRESS IN BRAIN RESEARCH 2004; 145:207-31. [PMID: 14650918 DOI: 10.1016/s0079-6123(03)45015-2] [Citation(s) in RCA: 381] [Impact Index Per Article: 18.1] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/03/2022]
Affiliation(s)
- Michael E Hasselmo
- Department of Psychology, Center for Memory and Brain, Program in Neuroscience, Boston University, 2 Cummington St., Boston, MA 02215, USA.
| | | |
Collapse
|
|
12
|
Oda S, Kuroda M, Kakuta S, Tanihata S, Ishikawa Y, Kishi K. Ultrastructure of ascending cholinergic terminals in the anteroventral thalamic nucleus of the rat: a comparison with the mammillothalamic terminals. Brain Res Bull 2003; 59:473-83. [PMID: 12576145 DOI: 10.1016/s0361-9230(02)00964-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
In this study, to identify the ultrastructure and distribution of ascending cholinergic afferent terminals in the anteroventral thalamic nucleus, we used an anti-vesicular acetylcholine transporter antibody as marker of cholinergic afferents, and characterized the immunoreactive terminals at the ultrastructural level. We then compared the distribution pattern of the cholinergic terminals and that of the mammillothalamic terminals identified by anterograde transport of a tracer injected into the mammillary body. The cholinergic terminals were small, and formed both symmetrical and asymmetrical synaptic contacts throughout the dendritic arborizations, particularly in the distal region. This distribution pattern differed from that of mammillothalamic terminals, that were of LR (large terminal containing round synaptic vesicles) type and were preferentially distributed in the proximal region of dendrites. We also found relatively numerous cholinergic terminals making contact directly with immunonegative excitatory terminals, both LR and SR (small terminal containing round vesicles) terminals, without clear postsynaptic specialization. A few cholinergic terminals even seemed to form a synaptic complex with the LR or SR terminals. These findings suggest that the ascending cholinergic afferents in the anteroventral thalamic nucleus can effectively modulate excitatory inputs from both the mammillothalamic and corticothalamic terminals, in close vicinity to a synaptic site.
Collapse
Affiliation(s)
- Satoko Oda
- Department of Anatomy, Toho University School of Medicine, Tokyo, Japan.
| | | | | | | | | | | |
Collapse
|
|
13
|
Castro-Alamancos MA. Different temporal processing of sensory inputs in the rat thalamus during quiescent and information processing states in vivo. J Physiol 2002; 539:567-78. [PMID: 11882688 PMCID: PMC2290158 DOI: 10.1113/jphysiol.2001.013283] [Citation(s) in RCA: 106] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
Sensory inputs from the whiskers reach the primary somatosensory thalamus through the medial lemniscus tract. The main role of the thalamus is to relay these sensory inputs to the neocortex according to the regulations dictated by behavioural state. Intracellular recordings in urethane-anaesthetized rats show that whisker stimulation evokes EPSP-IPSP sequences in thalamic neurons. Both EPSPs and IPSPs depress with repetitive whisker stimulation at frequencies above 2 Hz. Single-unit recordings reveal that during quiescent states thalamic responses to repetitive whisker stimulation are suppressed at frequencies above 2 Hz, so that only low-frequency sensory stimulation is relayed to the neocortex. In contrast, during activated states, induced by stimulation of the brainstem reticular formation or application of acetylcholine in the thalamus, high-frequency whisker stimulation at up to 40 Hz is relayed to the neocortex. Sensory suppression is caused by the depression of lemniscal EPSPs in relatively hyperpolarized thalamocortical neurons. Sensory suppression is abolished during activated states because thalamocortical neurons depolarize and the depressed lemniscal EPSPs are able to reach firing threshold. Strong IPSPs may also contribute to sensory suppression by hyperpolarizing thalamocortical neurons, but during activated states IPSPs are strongly reduced altogether. The results indicate that the synaptic depression of lemniscal EPSPs and the level of depolarization of thalamocortical neurons work together in thalamic primary sensory pathways to suppress high-frequency sensory inputs during non-activated (quiescent) states while permitting the faithful relay of high-frequency sensory information during activated (processing) states.
Collapse
Affiliation(s)
- Manuel A Castro-Alamancos
- Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A2B4, Canada.
| |
Collapse
|
|
14
|
Castro-Alamancos MA. Properties of primary sensory (lemniscal) synapses in the ventrobasal thalamus and the relay of high-frequency sensory inputs. J Neurophysiol 2002; 87:946-53. [PMID: 11826059 DOI: 10.1152/jn.00426.2001] [Citation(s) in RCA: 110] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
The main role of the thalamus is to relay sensory inputs to the neocortex. In the primary somatosensory thalamus (ventrobasal thalamus), sensory inputs deliver tactile information through the medial lemniscus tract. The transmission of sensory information through this pathway is affected by behavioral state. For instance, the relay of high-frequency somatosensory inputs through the thalamus is suppressed during anesthesia or quiescent states but allowed during behaviorally activated states. This change may be due to the effects of modulators on the efficacy of lemniscal synapses. Here I show that lemniscal synapses of adult rodents studied in vitro produce large amplitude-highly secure unitary excitatory postsynaptic potentials (EPSPs), which depress in response to repetitive stimulation at frequencies >2 Hz. Acetylcholine and norepinephrine, which are important thalamic modulators, have no effect on the efficacy of lemniscal EPSPs but reduce evoked inhibitory postsynaptic potentials and corticothalamic EPSPs. Although acetylcholine and norepinephrine do not affect lemniscal synapses, the postsynaptic depolarization they produce on thalamocortical neurons serves to warrant the relay of lemniscal inputs at high-frequency rates by bringing the depressed lemniscal EPSPs close to firing threshold. In conclusion, acetylcholine and norepinephrine released during activated states selectively enhance sensory transmission through the lemniscal pathway by depolarizing thalamocortical neurons and simultaneously depressing the other afferent pathways.
Collapse
Affiliation(s)
- Manuel A Castro-Alamancos
- Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Room WB210, Montreal, Quebec H3A 2B4, Canada.
| |
Collapse
|
|
15
|
Abstract
Data from in vivo and in vitro experiments are discussed to emphasize that synaptic activities in neocortex and thalamus have a decisive impact on intrinsic neuronal properties in intact-brain preparations under anesthesia and even more so during natural states of vigilance. Thus the firing patterns of cortical neuronal types are not inflexible but may change with the level of membrane potential and during periods rich in synaptic activity. The incidences of some cortical cell classes (defined by their responses to depolarizing current pulses) are different in isolated cortical slabs in vivo or in slices maintained in vitro compared with the intact cortex of naturally awake animals. Network activities, which include the actions of generalized modulatory systems, have a profound influence on the membrane potential, apparent input resistance, and backpropagation of action potentials. The analysis of various oscillatory types leads to the conclusion that in the intact brain, there are no "pure" rhythms, generated in simple circuits, but complex wave sequences (consisting of different, low- and fast-frequency oscillations) that result from synaptic interactions in corticocortical and corticothalamic neuronal loops under the control of activating systems arising in the brain stem core or forebrain structures. As an illustration, it is shown that the neocortex governs the synchronization of network or intrinsically generated oscillations in the thalamus. The rhythmic recurrence of spike bursts and spike trains fired by thalamic and cortical neurons during states of decreased vigilance may lead to plasticity processes in neocortical neurons. If these phenomena, which may contribute to the consolidation of memory traces, are not constrained by inhibitory processes, they induce seizures in which the neocortex initiates the paroxysms and controls their thalamic reflection. The results indicate that intact-brain preparations are necessary to investigate global brain functions such as behavioral states of vigilance and paroxysmal activities.
Collapse
Affiliation(s)
- M Steriade
- Laboratoire de Neurophysiologie, Faculté de Médecine, Université Laval, Quebec G1K 7P4, Canada.
| |
Collapse
|
|
16
|
Castro-Alamancos MA, Calcagnotto ME. High-pass filtering of corticothalamic activity by neuromodulators released in the thalamus during arousal: in vitro and in vivo. J Neurophysiol 2001; 85:1489-97. [PMID: 11287472 DOI: 10.1152/jn.2001.85.4.1489] [Citation(s) in RCA: 63] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
The thalamus is the principal relay station of sensory information to the neocortex. In return, the neocortex sends a massive feedback projection back to the thalamus. The thalamus also receives neuromodulatory inputs from the brain stem reticular formation, which is vigorously activated during arousal. We investigated the effects of two neuromodulators, acetylcholine and norepinephrine, on corticothalamic responses in vitro and in vivo. Results from rodent slices in vitro showed that acetylcholine and norepinephrine depress the efficacy of corticothalamic synapses while enhancing their frequency-dependent facilitation. This produces a stronger depression of low-frequency responses than of high-frequency responses. The effects of acetylcholine and norepinephrine were mimicked by muscarinic and alpha(2)-adrenergic receptor agonists and blocked by muscarinic and alpha-adrenergic antagonists, respectively. Stimulation of the brain stem reticular formation in vivo also strongly depressed corticothalamic responses. The suppression was very strong for low-frequency responses, which do not produce synaptic facilitation, but absent for high-frequency corticothalamic responses. As in vitro, application of muscarinic and alpha-adrenergic antagonists into the thalamus in vivo abolished the suppression of corticothalamic responses induced by stimulating the reticular formation. In conclusion, cholinergic and noradrenergic activation during arousal high-pass filters corticothalamic activity. Thus, during arousal only high-frequency inputs from the neocortex are allowed to reach the thalamus. Neuromodulators acting on corticothalamic synapses gate the flow of cortical activity to the thalamus as dictated by behavioral state.
Collapse
Affiliation(s)
- M A Castro-Alamancos
- Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada.
| | | |
Collapse
|
|
17
|
Oda S, Kuroda M, Kakuta S, Kishi K. Differential immunolocalization of m2 and m3 muscarinic receptors in the anteroventral and anterodorsal thalamic nuclei of the rat. Brain Res 2001; 894:109-20. [PMID: 11245821 DOI: 10.1016/s0006-8993(01)01986-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
In this study, to identify the precise localization of m2 and m3 muscarinic receptors in the anteroventral and anterodorsal thalamic nuclei of the rat, we used receptor-subtype-specific antibodies and characterized their immunolocalization patterns by light and electron microscopy. Many m2-positive neurons were distributed throughout these nuclei. Ultrastructural analysis showed that more than 30% of m2-positive dendritic profiles in these nuclei are proximal dendritic shafts. Moreover, a few m2-positive fiber terminals were found only in the anterodorsal thalamic nucleus. These m2-positive terminals were large (1.10+/-0.30 microm in diameter) and formed asymmetrical synapses with dendritic profiles. The m3-positive neurons were also distributed in both nuclei, and the m3-positive neuropil exhibited a significant staining gradient, with the most intense staining in the ventrolateral part of the anteroventral thalamic nucleus. This region receives the densest cholinergic input originating from the dorsal tegmental region. At the ultrastructural level, the majority of m3-positive dendritic profiles were more distal regions of the dendrites compared to the m2 receptors in the anteroventral thalamic nucleus. However, no significant difference in the intradendritic distribution pattern between m2 and m3 receptors was found in the anterodorsal thalamic nucleus, which receives no cholinergic input. These findings show the differential localization of m2 and m3 receptors in the anteroventral and anterodorsal thalamic nuclei, and suggest that the m3 receptors are spatially more closely associated with ascending cholinergic afferent fibers in the anteroventral thalamic nucleus.
Collapse
Affiliation(s)
- S Oda
- Department of Anatomy, Toho University School of Medicine, Omori Nishi 5-21-16, Ota-ku, 143-8540, Tokyo, Japan.
| | | | | | | |
Collapse
|
|
18
|
Abstract
The traditional specificity theory of pain perception holds that pain involves a direct transmission system from somatic receptors to the brain. The amount of pain perceived, moreover, is assumed to be directly proportional to the extent of injury. Recent research, however, indicates far more complex mechanisms. Clinical and experimental evidence shows that noxious stimuli may sensitize central neural structures involved in pain perception. Salient clinical examples of these effects include amputees with pains in a phantom limb that are similar or identical to those felt in the limb before it was amputated, and patients after surgery who have benefited from preemptive analgesia which blocks the surgery-induced afferent barrage and/or its central consequences. Experimental evidence of these changes is illustrated by the development of sensitization, wind-up, or expansion of receptive fields of CNS neurons, as well as by the enhancement of flexion reflexes and the persistence of pain or hyperalgesia after inputs from injured tissues are blocked. It is clear from the material presented that the perception of pain does not simply involve a moment-to-moment analysis of afferent noxious input, but rather involves a dynamic process that is influenced by the effects of past experiences. Sensory stimuli act on neural systems that have been modified by past inputs, and the behavioral output is significantly influenced by the "memory" of these prior events. An increased understanding of the central changes induced by peripheral injury or noxious stimulation should lead to new and improved clinical treatment for the relief and prevention of pathological pain.
Collapse
Affiliation(s)
- R Melzack
- Department of Psychology, McGill University, Montreal, Quebec, Canada
| | | | | | | |
Collapse
|
|
19
|
Rome HP, Rome JD. Limbically Augmented Pain Syndrome (LAPS): Kindling, Corticolimbic Sensitization, and the Convergence of Affective and Sensory Symptoms in Chronic Pain Disorders. PAIN MEDICINE 2000; 1:7-23. [PMID: 15101960 DOI: 10.1046/j.1526-4637.2000.99105.x] [Citation(s) in RCA: 102] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
There is abundant clinical evidence that depression occurs with high frequency among chronic pain patients. When compared with other serious medical disorders, the prevalence of depression in chronic pain appears high. The fundamental reason for this association is unknown. Theories have attempted to explain the link between pain and depression in terms of psychologic mechanisms. Other theories highlight shared neurobiologic substrates. However, a comprehensive theory integrating biologic and psychologic viewpoints remains elusive. In this article, we draw on research on neuroplastic processes in corticolimbic structures to model the linkage between the sensory and affective domains of pain. Our hypothesis is based on kindling experiments in animals that elucidate the complex neurobiologic mechanisms that transduce exteroceptive and interoceptive stimuli into "memory" at the cellular/synaptic level. This experimental model has found application in the affective disorders to explain how a person's history of exposure to psychologic trauma configures the neurobiologic substrate for later-amplified pathologic response. In applying kindling research to pain, we begin by reviewing the literature on nociception-induced neuroplasticity at the corticolimbic level. We suggest that kindling and related models of neuroplasticity can be used to describe ways in which exposure to a noxious stimulus may, under certain conditions, lead to a sensitized corticolimbic state. This sensitized state can be described in terms of the kindling properties of amplification, spontaneity, neuroanatomic spreading, and cross-sensitization. A case example illustrates how these properties offer a neurobiologic framework for understanding the sensory/affective/behavioral symptom complex seen in a subset of chronic pain patients. These patients are characterized by atypical and treatment-refractory pain complaints, in association with disturbances of mood, sleep, energy, libido, memory/concentration, behavior, and stress intolerance. We introduce the term "limbically augmented pain syndrome" to describe this symptom complex.
Collapse
Affiliation(s)
- H P Rome
- Pacific Pain Treatment Centers, Oakland, CA 94618, USA
| | | |
Collapse
|
|
20
|
Rodrigo-Angulo ML, Rodriguez-Veiga E, Reinoso-Suárez F. Serotonergic connections to the ventral oral pontine reticular nucleus: implication in paradoxical sleep modulation. J Comp Neurol 2000; 418:93-105. [PMID: 10701758 DOI: 10.1002/(sici)1096-9861(20000228)418:1<93::aid-cne7>3.0.co;2-1] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Cholinergic microstimulation of the ventral part of the oral pontine reticular nucleus (vRPO) in cats generates and maintains paradoxical sleep. The implication of rostral raphe nuclei in modulating the sleep-wakefulness cycle has been based on their serotonergic projections to the pontine structures responsible for the induction of paradoxical sleep. However, serotonergic neurons have also been described in brainstem structures other than the raphe nuclei. The aim of the present work is to trace the origin of the serotonergic afferents to the vRPO and to the locus coeruleus alpha and perilocus coeruleu alpha nuclei, closely related with different paradoxical sleep events. Anterograde and retrograde horseradish peroxidase conjugated with wheat germ agglutinin tracer injections in these nuclei in cats were combined with serotonin antiserum immunohistochemistry. Our results demonstrate that reciprocal connections linking the rostral raphe nuclei to those oral pontine nuclei are scarce. The percentage of double-labeled neurons after injections in the vRPO averaged 18% in rostral raphe nuclei, while a level of 82% was estimated in mesopontine tegmentum structures other than the raphe nuclei. These results showed that the main source of serotonin to the vRPO, implicated in generation and maintenance of paradoxical sleep, arises from these mesopontine tegmentum structures. This indicates that the serotonin modulation of paradoxical sleep could be the result of activation in non-raphe mesopontine tegmentum structures. The existence of a complicated network in the vRPO, which maintains a balance between different neurotransmitters responsible for the generation and alternance of paradoxical sleep episodes, is discussed.
Collapse
Affiliation(s)
- M L Rodrigo-Angulo
- Departamento de Morfología, Facultad de Medicina, Universidad Autónoma de Madrid, Spain
| | | | | |
Collapse
|
|
21
|
Abstract
Recent immunoelectron microscopic studies have revealed a low frequency of synaptic membrane differentiations on ACh (ChAT-immunostained) axon terminals (boutons or varicosities) in adult rat cerebral cortex, hippocampus and neostriatum, suggesting that, besides synaptic transmission, diffuse transmission by ACh prevails in many regions of the CNS. Cytological analysis of the immediate micro-environment of these ACh terminals, as well as currently available immunocytochemical data on the cellular and subcellular distribution of ACh receptors, is congruent with this view. At least in brain regions densely innervated by ACh neurons, a further aspect of the diffuse transmission paradigm is envisaged: the existence of an ambient level of ACh in the extracellular space, to which all tissue elements would be permanently exposed. Recent experimental data on the various molecular forms of AChE and their presumptive role at the neuromuscular junction support this hypothesis. As in the peripheral nervous system, degradation of ACh by the prevalent G4 form of AChE in the CNS would primarily serve to keep the extrasynaptic, ambient level of ACh within physiological limits, rather than totally eliminate ACh from synaptic clefts. Long-lasting and widespread electrophysiological effects imputable to ACh in the CNS might be explained in this manner. The notions of diffuse transmission and of an ambient level of ACh in the CNS could also be of clinical relevance, in accounting for the production and nature of certain cholinergic deficits and the efficacy of substitution therapies.
Collapse
Affiliation(s)
- L Descarries
- Département de physiologie, Faculté de médecine, Université de Montréal, QC, Canada.
| | | | | |
Collapse
|
|
22
|
Steriade M, Timofeev I. Short-term plasticity during intrathalamic augmenting responses in decorticated cats. J Neurosci 1997; 17:3778-95. [PMID: 9133397 PMCID: PMC6573710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
The intrathalamic mechanisms of frequency-dependent augmenting responses were investigated in decorticated cats by means of intracellular recordings from thalamocortical (TC) neurons in ventrolateral (VL) nucleus, including simultaneous impalements from two TC neurons. Pulse trains (10 Hz) applied to VL nucleus elicited two types of augmenting responses: (1) in 68% of cells, the incremental responses occurred on a progressive depolarization associated with the decrease in IPSPs produced by preceding stimuli in the train; (2) in the remaining cells, progressively growing low-threshold (LT) responses resulted from the enhancement of Cl--dependent IPSPs, giving rise to postinhibitory rebound bursts, followed by a self-sustained sequence of spindle waves. Although in some TC cells the augmenting responses developed from LT responses once the latter reached a given level of depolarization, other neurons displayed augmenting responses immediately after the early antidromic spike that depolarized the neuron to the required level, without an intermediate step of LT rebound. Repeated pulse trains led to a progressive and persistent increase in slow depolarizing responses of TC cells, as well as to a persistent and prolonged decrease in the amplitudes of the IPSPs. On the basis of parallel experiments, we propose that the two types of augmentation in TC cells are a result of contrasting responses of thalamic reticular neurons evoked by repetitive thalamic stimuli: decremental responses, which may account for disinhibition leading to depolarizing responses in TC cells, and incremental responses, explaining the progressive hyperpolarization of TC cells. These data demonstrate that frequency-dependent changes in neuronal excitability are present in the thalamus of a decorticated hemisphere and suggest that short-term plasticity processes in the gateway to the cerebral cortex may decisively influence cortical excitability during repetitive responses.
Collapse
Affiliation(s)
- M Steriade
- Laboratoire de Neurophysiologie, Faculté de Médecine, Université Laval, Quebec, Canada G1K 7P4
| | | |
Collapse
|
|
23
|
Affiliation(s)
- M Steriade
- Laboratoire de Neurophysiologie, Départment de Physiologie, Université Laval, Quebec, Canada
| |
Collapse
|
|
24
|
Van Groen T, Wyss JM. Projections from the anterodorsal and anteroventral nucleus of the thalamus to the limbic cortex in the rat. J Comp Neurol 1995; 358:584-604. [PMID: 7593752 DOI: 10.1002/cne.903580411] [Citation(s) in RCA: 167] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
The present study characterized the projections of the anterodorsal (AD) and the anteroventral (AV) thalamic nuclei to the limbic cortex. Both AD and AV project to the full extent of the retrosplenial granular cortex in a topographic pattern. Neurons in caudal parts of both nuclei project to rostral retrosplenial cortex, and neurons in rostral parts of both nuclei project to caudal retrosplenial cortex. Within AV, the magnocellular neurons project primarily to the retrosplenial granular a cortex, whereas the parvicellular neurons project mainly to the retrosplenial granular b cortex. AD projections to retrosplenial cortex terminate in very different patterns than do AV projections: The AD projection terminates with equal density in layers I, III, and IV of the retrosplenial granular cortex, whereas, in contrast, the AV projections terminate very densely in layer Ia and less densely in layer IV. Further, both AD and AV project densely to the postsubicular, presubicular, and parasubicular cortices and lightly to the entorhinal (only the most caudal part) cortex and to the subiculum proper (only the most septal part). Rostral parts of AD project equally to all three subicular cortices, whereas neurons in caudal AD project primarily to the postsubicular cortex. Compared to AD, neurons in AV have a less extensive projection to the subicular cortex, and this projection terminates primarily in the postsubicular and presubicular cortices. Further, the AD projection terminates in layers I, II/III, and V of postsubiculum, whereas the AV projection terminates only in layers I and V.
Collapse
Affiliation(s)
- T Van Groen
- Department of Cell Biology, University of Alabama, Birmingham 35294, USA
| | | |
Collapse
|
|
25
|
Garcia-Rill E, Biedermann JA, Chambers T, Skinner RD, Mrak RE, Husain M, Karson CN. Mesopontine neurons in schizophrenia. Neuroscience 1995; 66:321-35. [PMID: 7477875 DOI: 10.1016/0306-4522(94)00564-l] [Citation(s) in RCA: 70] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Findings reported here show that there is a significant increase in the number of neurons in the pedunculopontine nucleus in most schizophrenic patients compared to age-matched controls. Nicotinamide adenine dinucleotide phosphate diaphorase histochemistry was used to label putative cholinergic neurons in the pedunculopontine nucleus and laterodorsal tegmental nucleus, while noradrenergic locus coeruleus neurons were labeled immunocytochemically using an antibody to tryosine hydroxylase. Cell counts of these neuronal groups were carried out using a Biographics image analysis system. We found significantly increased cell numbers in the pedunculopontine nucleus of schizophrenic patients compared to controls. The number of laterodorsal tegmental nucleus neurons was increased but this was not statistically significant. However, the total cell counts for pedunculopontine and laterodorsal tegmental nuclei were significantly higher in schizophrenic subjects. The number of locus coeruleus noradrenergic neurons was similar in both groups. These results implicate the brainstem reticular formation as a pathophysiological site in at least some patients with schizophrenia. In addition, these findings suggest a developmental etiology for the disease and account for some, but not all, of the symptoms of schizophrenia, including sensory gating abnormalities, sleep-wake disturbances and, perhaps, hallucinations. Overdriving of thalamic and substantia nigra function by cholinergic afferents from the midbrain may account for some of the symptoms seen in schizophrenia. These findings suggest that, at least in some schizophrenic patients, there is an increased number of neurons in the cholinergic arm of the reticular activating system. This may explain some of the symptoms of schizophrenia and points to a prenatal disturbance as one of the possible causes of the disease.
Collapse
Affiliation(s)
- E Garcia-Rill
- Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock 72205, USA
| | | | | | | | | | | | | |
Collapse
|
|
26
|
Brown TJ, Shipley LA. Determination of xanomeline (LY246708 tartrate), an investigational agent for the treatment of Alzheimer's disease, in rat and monkey plasma by capillary gas chromatography with nitrogen-phosphorus detection. JOURNAL OF CHROMATOGRAPHY. B, BIOMEDICAL APPLICATIONS 1995; 665:337-44. [PMID: 7795813 DOI: 10.1016/0378-4347(94)00538-g] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
A GC method is described for the determination of xanomeline (LY246708 tartrate) and selected metabolites in rat and monkey plasma. The analytes, including an internal standard, were extracted from plasma at basic pH with hexane. The organic extract was evaporated to dryness and the residue was reconstituted in hexane. The analytes were separated from metabolites and endogenous substances using a DB1701 capillary column. The analytes were detected using nitrogen-phosphorus detection (NPD). The limit of quantitation was determined to be 8 ng/ml, and the response was linear from 8 to 800 ng/ml. The method has been successfully applied to rat and monkey samples pursuant to the development of xanomeline as an agent for the symptomatic treatment of Alzheimer's disease.
Collapse
Affiliation(s)
- T J Brown
- Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
| | | |
Collapse
|
|
27
|
Reese NB, Garcia-Rill E, Skinner RD. Auditory input to the pedunculopontine nucleus: II. Unit responses. Brain Res Bull 1995; 37:265-73. [PMID: 7627569 DOI: 10.1016/0361-9230(95)00001-u] [Citation(s) in RCA: 55] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
The pedunculopontine nucleus (PPN) has been implicated in sleep-wake control, arousal responses, and motor functions. The PPN also has been implicated in the generation of the P1 middle-latency auditory-evoked potential. The present study was undertaken to determine the nature of the responsiveness of single neurons in and around the PPN following auditory stimulation. Somatosensory responsiveness also was tested in some cells. These results demonstrate a) the presence of a significant proportion of PPN neurons that respond to auditory click stimuli; b) two populations of neurons showing either low threshold/short latency/low habituation or high threshold/longer latency/high habituation; c) the responses of longer latency neurons precede the onset and peak of depth- and vertex-recorded middle-latency auditory-evoked potentials; d) thresholds of longer latency neurons similar to the threshold for wave A in the intact cat, the P13 potential in the intact rat, or the startle reflex; and e) convergent somatosensory and auditory responses at a similar latency in a number of PPN neurons. These findings suggest that neurons in and around the PPN may participate in auditory and somatosensory information processing related to arousal, and may contribute to the manifestation of the P1 auditory middle-latency evoked potential.
Collapse
Affiliation(s)
- N B Reese
- Department of Physical Therapy, University of Central Arkansas, Conway 72035, USA
| | | | | |
Collapse
|
|
28
|
Reese NB, Garcia-Rill E, Skinner RD. Auditory input to the pedunculopontine nucleus: I. Evoked potentials. Brain Res Bull 1995; 37:257-64. [PMID: 7627568 DOI: 10.1016/0361-9230(95)00002-v] [Citation(s) in RCA: 46] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
The pedunculopontine nucleus (PPN) has been implicated in sleep-wake control, arousal responses, and motor functions. The PPN also has been implicated in the generation of the P1 middle-latency auditory-evoked potential. The present study was undertaken to determine the topographical distribution, threshold, and response properties of depth-recorded potentials following auditory click stimulation. Experiments were conducted in both decerebrate cat and rat, with a view towards determining the presence of P1-like middle-latency auditory-evoked potentials in the midbrain of both species. These results demonstrate a) the presence in and around the PPN of a P1-like potential in the decerebrate rat similar to that described in the accompanying article as the P13 in the intact rat; b) the presence in and around the PPN of a P1-like potential in the decerebrate cat similar to that previously described by others as wave A in the intact cat; c) although thresholds for these potentials were similar to those of intact preparations, following frequencies were higher in the decerebrate preparations, i.e., responsiveness to repetitive stimulation was higher; and d) depth-recorded somatosensory-evoked potentials also were studied in the cat and found to show an evoked potential at a similar latency as middle-latency auditory depth-recorded potentials. These findings suggest that click stimulus-evoked, depth-recorded potentials are present in and around the PPN in the decerebrate rat and cat, i.e., in the absence of cortex, at a similar latency as in intact preparations.
Collapse
Affiliation(s)
- N B Reese
- Department of Physical Therapy, University of Central Arkansas, Conway 72035, USA
| | | | | |
Collapse
|
|
29
|
Vertes RP, Kocsis B. Projections of the dorsal raphe nucleus to the brainstem: PHA-L analysis in the rat. J Comp Neurol 1994; 340:11-26. [PMID: 8176000 DOI: 10.1002/cne.903400103] [Citation(s) in RCA: 138] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Early studies that used older tracing techniques reported exceedingly few projections from the dorsal raphe nucleus (DR) to the brainstem. The present report examined DR projections to the brainstem by use of the anterograde anatomical tracer Phaseolus vulgaris leucoagglutinin (PHA-L). DR fibers were found to terminate relatively substantially in several structures of the midbrain, pons, and medulla. The following pontine and midbrain nuclei receive moderate to dense projections from the DR: pontomesencephalic central gray, mesencephalic reticular formation, pedunculopontine tegmental nucleus, medial and lateral parabrachial nuclei, nucleus pontis oralis, nucleus pontis caudalis, locus coeruleus, laterodorsal tegmental nucleus, and raphe nuclei, including the central linear nucleus, median raphe nucleus, and raphe pontis. The following nuclei of the medulla receive moderately dense projections from the DR: nucleus gigantocellularis, nucleus raphe magnus, nucleus raphe obscurus, facial nucleus, nucleus gigantocellularis-pars alpha, and the rostral ventrolateral medullary area. DR fibers project lightly to nucleus cuneiformis, nucleus prepositus hypoglossi, nucleus paragigantocellularis, nucleus reticularis ventralis, and hypoglossal nucleus. Some differences were observed in projections from rostral and caudal parts of the DR. The major difference was that fibers from the rostral DR distribute more widely and heavily than do those from the caudal DR to structures of the medulla, including raphe magnus and obscurus, nucleus gigantocellularis-pars alpha, nucleus paragigantocellularis, facial nucleus, and the rostral ventrolateral medullary area. A role for the dorsal raphe nucleus in several brainstem controlled functions is discussed, including REM sleep and its events, nociception, and sensory motor control.
Collapse
Affiliation(s)
- R P Vertes
- Center for Complex Systems, Florida Atlantic University, Boca Raton 33431
| | | |
Collapse
|
|
30
|
Affiliation(s)
- M Davis
- Ribicoff Research Facilities of the Connecticut Mental Health Center, Department of Psychiatry, Yale University School of Medicine, New Haven 06508
| |
Collapse
|
|
31
|
Núñez A, Barrenechea C, Avendaño C. Spontaneous activity and responses to sensory stimulation in ventrobasal thalamic neurons in the rat: an in vivo intracellular recording and staining study. Somatosens Mot Res 1994; 11:89-98. [PMID: 8017148 DOI: 10.3109/08990229409028861] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Spontaneous activity and responses to sensory stimulation in ventrobasal (VB) thalamic neurons were studied in barbiturate-anesthetized rats through intracellular recordings. The recordings were carried out with micropipettes filled with K acetate KCl plus horseradish peroxidase (HRP), our KCl plus biocytin. Two types of spontaneous depolarizing events were observed: fast potentials (FPs), characterized by a low amplitude (5.3 +/- 1.8 mV [mean and standard deviation]), a fast rising slope (1.15 +/- 0.19 msec), and a short duration (8.47 +/- 0.89 msec); and slow potentials (SPs), characterized by a larger and more variable amplitude (9.1 +/- 5.6 mV) and a longer duration (62.5 +/- 27.2 msec), with a slower rising slope (26.2 +/- 6.4 msec). The potential changes elicited by sensory stimuli delivered manually were similar to those elicited by electronically gated short air jets to the receptive fields. FPs were evoked by sensory stimulation in 62.7% of the recorded neurons, and SPs in the remaining 37.3%. Both types of events could occur spontaneously in the same neuron, but only one of them was triggered by stimulation of the receptive field. Five neurons that were successfully stained with either HRP or biocytin were studied in detail. All were medium-sized stellate cells, with spine-like appendages sparsely distributed along slender radiating dendrites. The axons took a rostrolateral course across the VB, and all but one left one or two thin collaterals in the reticular thalamic nucleus. No overt morphological differences were observed between VB neurons that responded with FPS or SPs to sensory stimulation.
Collapse
Affiliation(s)
- A Núñez
- Departamento de Morfologia, Facultad de Medicina, Universidad Autónoma de Madrid, Spain
| | | | | |
Collapse
|
|
32
|
Pascoe JP, Kapp BS. Electrophysiology of the dorsolateral mesopontine reticular formation during Pavlovian conditioning in the rabbit. Neuroscience 1993; 54:753-72. [PMID: 8332260 DOI: 10.1016/0306-4522(93)90245-b] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Extracellular single-unit recording methods were used to study the activity of neurons within a restricted portion of the dorsolateral mesopontine reticular formation, an area which includes the parabrachial, pedunculopontine tegmental and cuneiform nuclei. Recordings were obtained during presentations of unfamiliar and familiar sensory stimuli, during Pavlovian differential conditioning procedures that elicited conditioned bradycardia, and while stimulating the amygdaloid central nucleus to identify neurons that projected to, or received projections from, the amygdaloid central nucleus. Activity in most dorsolateral mesopontine reticular neurons was altered during sensory stimulation, and the convergence of auditory and somatic inputs onto single neurons was common. Moreover, neural responses were often of a different magnitude and/or direction to auditory stimuli that were unfamiliar vs familiar vs reinforced (paired with pinna stimulation), and many of these differentially responsive neurons were activated orthodromically by stimulation of the amygdaloid central nucleus. In contrast, neurons activated antidromically by stimulation of the amygdaloid central nucleus were relatively quiescent during all phases of the experiment. Results are discussed in relation to current hypotheses concerning the functional significance of various neuronal subpopulations within the dorsolateral mesopontine reticular formation during Pavlovian conditioning.
Collapse
Affiliation(s)
- J P Pascoe
- Department of Psychology, University of Vermont, Burlington 05405
| | | |
Collapse
|
|
33
|
Coderre TJ, Katz J, Vaccarino AL, Melzack R. Contribution of central neuroplasticity to pathological pain: review of clinical and experimental evidence. Pain 1993; 52:259-285. [PMID: 7681556 DOI: 10.1016/0304-3959(93)90161-h] [Citation(s) in RCA: 1300] [Impact Index Per Article: 40.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Peripheral tissue damage or nerve injury often leads to pathological pain processes, such as spontaneous pain, hyperalgesia and allodynia, that persist for years or decades after all possible tissue healing has occurred. Although peripheral neural mechanisms, such as nociceptor sensitization and neuroma formation, contribute to these pathological pain processes, recent evidence indicates that changes in central neural function may also play a significant role. In this review, we examine the clinical and experimental evidence which points to a contribution of central neural plasticity to the development of pathological pain. We also assess the physiological, biochemical, cellular and molecular mechanisms that underlie plasticity induced in the central nervous system (CNS) in response to noxious peripheral stimulation. Finally, we examine theories which have been proposed to explain how injury or noxious stimulation lead to alterations in CNS function which influence subsequent pain experience.
Collapse
Affiliation(s)
- Terence J Coderre
- Pain Mechanisms Laboratory, Clinical Research Institute of Montreal, MontrealCanada Département de Médecine, Université de Montréal, MontrealCanada Department of Psychology, McGill University, MontrealCanada Department of Psychology, Toronto General Hospital, TorontoCanada Departments of Behavioral Science and Anaesthesia, University of Toronto, TorontoCanada
| | | | | | | |
Collapse
|
|
34
|
Steriade M. Modulation of information processing in thalamocortical systems: chairman's introductory remarks. PROGRESS IN BRAIN RESEARCH 1993; 98:341-3. [PMID: 7902594 DOI: 10.1016/s0079-6123(08)62417-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Affiliation(s)
- M Steriade
- Laboratoire de Neurophysiologie, Faculté de Médecine, Université Laval, Quebec, Canada
| |
Collapse
|
|
35
|
Steriade M. Cholinergic blockage of network- and intrinsically generated slow oscillations promotes waking and REM sleep activity patterns in thalamic and cortical neurons. PROGRESS IN BRAIN RESEARCH 1993; 98:345-55. [PMID: 8248523 DOI: 10.1016/s0079-6123(08)62418-8] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Affiliation(s)
- M Steriade
- Laboratoire de Neurophysiologie, Faculté de Médecine, Université Laval, Quebec, Canada
| |
Collapse
|
|
36
|
Albrecht D, Davidowa H. Extraretinal modulation of geniculate neuronal activity by conditioning. PROGRESS IN BRAIN RESEARCH 1993; 95:271-86. [PMID: 8493338 DOI: 10.1016/s0079-6123(08)60375-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Affiliation(s)
- D Albrecht
- Institute of Physiology, Medical School Charité, Humboldt University of Berlin, Germany
| | | |
Collapse
|
|
37
|
Mello LE, Tan AM, Finch DM. Convergence of projections from the rat hippocampal formation, medial geniculate and basal forebrain onto single amygdaloid neurons: an in vivo extra- and intracellular electrophysiological study. Brain Res 1992; 587:24-40. [PMID: 1525648 DOI: 10.1016/0006-8993(92)91425-e] [Citation(s) in RCA: 45] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
We recorded extra- and intracellular responses from rat amygdaloid neurons in vivo after electrical stimulation of the hippocampal formation (dentate gyrus, hippocampal fields CA3 and CA4, entorhinal cortex, subicular complex); medial geniculate; and basal forebrain (diagonal band, ventral pallidum, olfactory tubercle, nucleus accumbens, bed nucleus of stria terminalis, lateral preoptic area, substantia innominata). Stimulation of hippocampal formation structures evoked IPSPs or EPSP-IPSP sequences in which the IPSP had a lower threshold than the EPSP. Recordings from candidate inhibitory neurons in the amygdala indicated that excitatory afferents from the hippocampal formation contact both amygdaloid inhibitory and principal neurons (feedforward inhibition), and that the inhibitory neurons have a lower threshold of activation. Medial geniculate stimulation also evoked EPSP-IPSP sequences. In marked contrast to these results, stimulation of basal forebrain structures evoked short latency IPSPs in amygdaloid neurons. This provides the first physiological evidence for direct inhibition of the amygdala by the basal forebrain. Basal forebrain stimulation also evoked EPSP-IPSP sequences in amygdaloid neurons. Individual amygdaloid neurons could show responses to stimulation of the hippocampal formation, basal forebrain, and medial geniculate, indicating that synaptic input from these areas converges onto single amygdaloid cells. The findings provide further information about the synaptic organization of afferents to the amygdala, and indicate that single amygdaloid neurons play a role in the synaptic integration of input from these diverse sources.
Collapse
Affiliation(s)
- L E Mello
- Brain Research Institute, Reed Neurological Research Center, University of California, Los Angeles 90024
| | | | | |
Collapse
|
|
38
|
Vaccarino AL, Melzack R. Temporal processes of formalin pain: differential role of the cingulum bundle, fornix pathway and medial bulboreticular formation. Pain 1992; 49:257-271. [PMID: 1608649 DOI: 10.1016/0304-3959(92)90150-a] [Citation(s) in RCA: 88] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Subcutaneous injection of formalin produces a characteristic biphasic pain response. An early phase develops in the first 5 min after injection; the pain then decreases for 10-15 min, followed by a gradual rise to a stable plateau that lasts about 1 h. Rats were injected with 1 microliter of 2% lidocaine or saline into the anterior cingulum bundle at 0 (immediately), 10 or 30 min prior to formalin injection, or 10, 20 or 30 min after formalin injection, and tested for analgesia in the late phase of the formalin test, 30-70 min after formalin injection. A time-dependent increase in analgesia was obtained when lidocaine was injected into the cingulum at periods ranging from 10 to 30 min after formalin injection, reflecting an anaesthetic duration of less than 20 min. When lidocaine was injected 0 or 10 min prior to formalin injection, a time-dependent increase in analgesia in the late phase was again observed. In these groups, lidocaine should have blocked cingulum activity during the early but not the late phase. The role of the fornix pathway and the medial bulboreticular formation in mediating formalin pain was also examined. Lidocaine produced analgesia in the late phase when injected into the fornix prior to formalin injection but had no effect when administered after it. In contrast, when lidocaine was injected into the medial bulboreticular formation it produced analgesia in the late phase when administered after formalin injection, but not prior to it. Taken together, these results suggest that the late pain response to formalin is in part dependent upon plasticity in the central nervous system which occurs during the transient early phase.
Collapse
Affiliation(s)
- Anthony L Vaccarino
- Department of Psychology, University of California, Los Angeles, CA 90024 USA Department of Psychology, McGill University, Quebec H3A 1B1 Canada
| | | |
Collapse
|
|
39
|
Curró Dossi R, Paré D, Steriade M. Various types of inhibitory postsynaptic potentials in anterior thalamic cells are differentially altered by stimulation of laterodorsal tegmental cholinergic nucleus. Neuroscience 1992; 47:279-89. [PMID: 1641124 DOI: 10.1016/0306-4522(92)90244-v] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
The effects of stimulating the laterodorsal tegmental cholinergic nucleus upon inhibitory postsynaptic potentials recorded in relay cells of the anterior thalamic complex were studied in urethane-anesthetized cats. The inhibitory postsynaptic potentials induced in anterior thalamic relay cells by stimulating mammillary nuclei or retrosplenial cortex are generated by local-circuit inhibitory neurons since this nuclear complex is devoid of afferents from the other intrathalamic source of inhibition, the reticular thalamic nucleus. In a parallel study from this laboratory, it has been shown that cortical stimulation elicits a biphasic inhibitory postsynaptic potential consisting of two (A and B) components attributed to axonal firing of local interneurons, whereas mammillary stimulation elicits, in addition to the A-B sequence, an earlier component (a) presumably generated by presynaptic dendrites in thalamic glomeruli. In the present study, short pulse-trains applied to the laterodorsal tegmental nucleus diminished the amplitudes of A and B inhibitory components or completely suppressed them. The B component was more sensitive to the depressive effect. By contrast with the changes of the A and B components, the mammillary-evoked a inhibitory component was not reduced and, in many instances, was enhanced following laterodorsal tegmental stimulation. The effects of laterodorsal tegmental stimulation survived monoamine depletion by reserpine. We suggest that mesopontine cholinergic depressive actions on A and B inhibitory postsynaptic potentials may be due to an increased conductance in thalamocortical cells during the short-lasting nicotinic action combined with a somatic hyperpolarization of local-circuit cells, whereas the enhancement of the earliest (a) inhibitory postsynaptic potential reflects a concomitant potentiating action at the level of intraglomerular presynaptic dendrites.
Collapse
Affiliation(s)
- R Curró Dossi
- Laboratoire de Neurophysiologie, Faculté de Médecine, Université Laval, Canada
| | | | | |
Collapse
|
|
40
|
Gabriel M, Vogt BA, Kubota Y, Poremba A, Kang E. Training-stage related neuronal plasticity in limbic thalamus and cingulate cortex during learning: a possible key to mnemonic retrieval. Behav Brain Res 1991; 46:175-85. [PMID: 1664730 DOI: 10.1016/s0166-4328(05)80111-1] [Citation(s) in RCA: 58] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
This study is part of an ongoing project concerned with the analysis of the neural substrates of discriminative avoidance learning in rabbits. Multi-unit activity was recorded in 5 anterior and lateral thalamic nuclei and in 4 layers of 2 posterior cingulate cortical areas (29c/d and 29b) during learning. The rabbits learned to step in response to a warning tone to avoid a foot-shock, and to ignore a different tone not followed by shock. Excitatory training-induced unit activity (TIA, increased tone-elicited activity during training relative to a pretraining session with unpaired tone-shock presentations) and/or discriminative TIA (greater discharges to the warning than to the safe tone) developed during training in 11 of the 13 areas. Discriminative TIA in the thalamic nuclei increased monotonically as learning occurred. Anterodorsal (AD) thalamic excitatory TIA peaked in an early stage (the first session of training), laterodorsal thalamic and parvocellular anteroventral (AVp) excitatory TIA peaked in an intermediate stage (the session of the first behavioral discrimination), and magnocellular anteroventral (AVm) and anteromedial (AM) thalamic excitatory TIA peaked in a late stage (the session in which asymptotic behavioral discrimination first occurred). The excitatory TIA in these nuclei declined as training continued beyond the stage in which the peak occurred. Peaks of excitatory TIA developed in area 29c/d of posterior cingulate cortex in the early (layer IV), intermediate (layers I-III and V) and late (layer IV) training stages, as just defined. Only layer IV in area 29b of posterior cingulate cortex exhibited a peak of excitatory TIA, which occurred in the early and intermediate training stages. As in limbic thalamus, discriminative TIA increased monotonically over training stages in layers V and VI of areas 29c/d and in layer VI of area 29b. However, layers I-III and IV in area 29c exhibited peak discriminative TIA in the intermediate and late training stages, respectively. Lesion studies indicate that limbic thalamus and cingulate cortex are essential for learning. The peaks represent a unique topographic pattern of thalamic and cortical excitation elicited by the CS+. It is proposed that the peaks constitute a retrieval pattern, i.e. a unique topographic array of excitation. This pattern encodes the spatio-temporal context which defines the learning situation and is necessary for recall and output of the learned response.
Collapse
Affiliation(s)
- M Gabriel
- Department of Psychology, University of Illinois, Urbana 61801
| | | | | | | | | |
Collapse
|
|
41
|
McKinney M, Coyle JT. The potential for muscarinic receptor subtype-specific pharmacotherapy for Alzheimer's disease. Mayo Clin Proc 1991; 66:1225-37. [PMID: 1749291 DOI: 10.1016/s0025-6196(12)62474-4] [Citation(s) in RCA: 59] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
In several neurodegenerative disorders, including Alzheimer's disease, a loss of the cholinergic projections of the basal forebrain to the cerebral cortex and hippocampus occurs. Studies of the anatomic and physiologic characteristics of these ascending cholinergic systems suggest that they are important in processing information and in memory function. Muscarinic receptors are situated at various critical control points in these pathways. Activation of postsynaptic muscarinic receptors often increases the excitability of neurons; thus, the signal-to-noise ratio for sensory processing is enhanced. In addition, muscarinic receptors negatively control cholinergic tone at presynaptic sites. Molecular biologic methods have disclosed the existence of five muscarinic receptors, which are coupled to different second messenger systems. The evidence reviewed suggests that at least four of the five muscarinic receptor genes are expressed as functional receptor proteins in the neocortex and hippocampal formation. On the basis of the current information about their pharmacologic properties and coupling mechanisms in nervous tissue, drugs that selectively affect subtypes of muscarinic receptors could enhance cortical cholinergic function and thereby ameliorate certain cognitive impairments in Alzheimer's disease.
Collapse
Affiliation(s)
- M McKinney
- Section of Neuropharmacology, Mayo Clinic Jacksonville, FL 32224
| | | |
Collapse
|
|
42
|
Karson CN, Garcia-Rill E, Biedermann J, Mrak RE, Husain MM, Skinner RD. The brain stem reticular formation in schizophrenia. Psychiatry Res 1991; 40:31-48. [PMID: 1682969 DOI: 10.1016/0925-4927(91)90027-n] [Citation(s) in RCA: 59] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Post-mortem brain tissue was obtained from four patients with schizophrenia and five controls to study cell groups in the brain stem reticular formation. Cholinergic neurons in the pedunculopontine nucleus (PPN) and lateral dorsal tegmental nucleus (LDT) were labeled using nicotinamide adenosine dinucleotide phosphate (NADPH)-diaphorase histochemistry, while catecholaminergic neurons of the locus ceruleus (LC) were labeled immunocytochemically using an antibody to tyrosine hydroxylase. In schizophrenic patients, there were increased numbers of neurons in the PPN labeled by NADPH-diaphorase and reduced cell size in the LC. These results implicate the reticular formation as a possible pathophysiological site for at least some patients with schizophrenia. This also suggests that some of the deficits observed may be based on faulty neurodevelopment.
Collapse
Affiliation(s)
- C N Karson
- University of Arkansas for Medical Sciences, Little Rock
| | | | | | | | | | | |
Collapse
|
|
43
|
|
|
44
|
Steriade M, Gloor P, Llinás RR, Lopes de Silva FH, Mesulam MM. Report of IFCN Committee on Basic Mechanisms. Basic mechanisms of cerebral rhythmic activities. ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY 1990; 76:481-508. [PMID: 1701118 DOI: 10.1016/0013-4694(90)90001-z] [Citation(s) in RCA: 768] [Impact Index Per Article: 21.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Affiliation(s)
- M Steriade
- Laboratoire de Neurophysiologie, Faculté de Médecine, Université Laval, Quebec, Canada
| | | | | | | | | |
Collapse
|