Functional Properties of Human Stem Cell-Derived Neurons in Health and Disease

Table 1

Dysfunction and treatment of diseased human stem cell-derived neurons.

Disease	Cell type(s)	Observed phenotypes	Refs	Treatment
Amyotrophic lateral sclerosis (ALS)	iPSC-derived motor neurons	Motor neurons derived from ALS iPSCs displayed hyperexcitability	[5]	Kv7 channel-activator retigabine reversed MN hyperexcitability
Bipolar disorder	Forebrain hPSNs	Increased AP frequency and amplitude in lithium-responsive and -nonresponsive hPSNs selectively responded to treatments (column 5)	[6]	Li^2+ reduced hyperexcitability in hPSNs from Li^2+-responsive patients; Lamotrigine reduced hyperexcitability in Li^2+-nonresponsive hPSNs
Down syndrome	Forebrain hPSNs	Decreased frequency (not amplitude) of spontaneous excitatory and inhibitory synaptic events	[7]	None reported
Dravet syndrome	Forebrain hPSNs	(i) Spike generation impaired in GABAergic neurons	[8]	Phenytoin reduced hyperexcitability
		(ii) Increased sodium currents	[9]
		(iii) Hyperexcitability/spontaneous bursting resembling epileptiform activity	[10]
Huntington’s disease	Forebrain and striatal hPSNs	CAG repeat length-dependent reductions in spiking associated with increased cell death	[11]	None reported
Phelan-McDermid syndrome (22q13 deletion)	Forebrain hPSNs	Selective reduction in amplitude and frequency of spontaneous excitatory postsynaptic currents (excitation-inhibition ratio altered)	[12]	Genetic expression of Shank3 or IGF1 treatment restored EPSCs
Psychiatric disease; (ASD/SCZ); (NRXN1 mutants)	Forebrain hPSNs and iNs	Impaired neurotransmitter release; reduced sEPSC frequency upregulation of presynaptic CASK protein	[2]	None reported
Rett syndrome	Glutamatergic hPSNs	Decreased activity-dependent calcium oscillations; Reduced frequency and amplitude of spontaneous synaptic currents	[13]	None reported
Spinal muscular atrophy (SMA)	iPSC-derived motor neurons	Hyperexcitability and impaired neurotransmission; Greater and lower voltage threshold for spike induction	[14]	Genetic correction reversed phenotypes
Timothy syndrome	Forebrain hPSNs	Increased action potential width; Greater elevations of intracellular calcium	[15]	None reported
Williams-Beuren syndrome	Forebrain hPSNs	Reduced AP amplitude and prolonged decay; no effect on other passive/active conductance nor mEPSCs	[16]	None reported