Importance of being Nernst: Synaptic activity and functional relevance in stem cell-derived neurons

Table 1 Stem cell-derived neurons characterized for synaptic activity

Cell type	Source	Technical approach	Post-synaptic measurement(days after differentiation)	Additional notes	Ref.
ESC	Human (BG01, BG03)	Stromal cell factors applied	mEPSCs (21)	Also dopaminergic	[254]
				Continued expression of NPC marker Msx1
	Human (WiCell H9, H1)	SHH application on ESCs or NPCs	mEPSCs, mIPSCs (30)	Also dopaminergic	[110]
	Human (H9 and SA121)	Dual SMAD inhibition, variable SHH, several additional neurotrophic factors	sEPSCs, sIPSCs (35)	SHH concentration-dependent GABAergic and glutamatergic, or dopaminergic fates	[240]
	Mouse (R1)	RA treatment, suspension culture	mEPSCs, mIPSCs (21)		[6,59,226]
	Mouse (J1)	FACS sorting for dopaminergic NPCs, SHH treatment	sEPSCs (22)	Also dopaminergic	[255]
NSC	Human (NSI-566RSC from fetal spinal cord)	9 component differentiation media	mEPSCs (12-48)		[256]
	Mouse (Adult C57/Bl6 SEZ)	BDNF treatment	mEPSCs, mIPSCs (11-28)	Perforated patch recording	[171]
iPSC	Human (normal and ALS fibroblasts)	Dual SMAD inhibition, RA and purmorphamine treatment	sEPSCs (21-42)	sEPSCs only detected with picrotoxin and 4-aminopyridine	[86]
	Human (normal and AD fibroblasts)	FACS sorting of NPCs, BDNF, GDNF and cAMP treatment	mIPSCs, mEPSCs (26)	Currents detected in approximately 40% of cells	[148]
iN	Human (postnatal and adult fibroblasts)	Two-stage Dox, bFGF, Noggin, GDNF, BDNF, forskolin treatments	mEPSCs (30)	Currents detected in 25%-43% of converted cells	[158]
	Mouse (perinatal tail tip fibroblasts)	Glial co-culture, FACS sorting	sEPSCs (15-27)		[156,157]
ESC + iPSC	Human (HES3, BioTime ESI, and WiCell H9 ESCs + melanocyte hiPSCs)	5 morphogenic factors, FACS sorting, glial co-culture	sIPSCs (42-84)	% of cells with currents increases over time	[28]
				Implanted neurons also received EPSCs
	Human (HUES9 ESCs + fibroblast hiPSCs)	Noggin and dorsomorphin treatment, recombinant human Dkk1 treatment of hiPSC EBs, glial co-culture	mEPSCs (35)	Currents detected in 33% of differentiated ESCs and 46% of differentiated iPSCs tested	[111]
	Human (WiCell H9 and SHEF4 ESCs + fibroblast hiPSCs)	3% O2	mEPSCs (35)	Mature AMPA and GABA profiles	[47,116]

ESC: Embryonic stem cell; NSC: Neural stem cell; iPSC: Induced pluripotent stem cell; ALS: Amyotrophic lateral sclerosis; AD: Alzheimer’s disease; SHH: Sonic hedgehog; NPC: Neural precursor cell; SMAD: Sma and Mad related proteins; RA: Retinoic acid; FACS: Fluorescence-activated cell sorting; BDNF: Brain-derived neurotrophic factor; GDNF: Glia-derived neurotrophic factor; iN: Induced neuron; cAMP: Cyclic adenosine monophosphate; bFGF: Basic fibroblast growth factor; mEPSC/mIPSC: Miniature excitatory/inhibitory post-synaptic current; sEPSC/sIPSC: Spontaneous excitatory/inhibitory post-synaptic current; GABA: Gamma aminobutyric acid; AMPA: Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid.