Figure 3.

Implantation of ESI-017 hNSCs Reduces Corticostriatal Hyperexcitability in R6/2 Mice

(A) Biocytin-filled (red, yellow arrow) hNSC that was recorded in the striatum and IHC with SC121 (green). Scale bar, 20 μm.

(B) Top trace: cell-attached recording of spontaneously firing hNSC. Bottom traces: sEPSCs and sIPSCs from hNSC. Recordings illustrate spontaneous inward and outward synaptic currents in the hNSC.

(C) sEPSCs and sIPSCs recorded in MSN.

(D) Biocytin-filled MSN (red) near a cluster of hNSCs (SC121 green). Scale bar, 20 μm.

(E) Recordings of sEPSCs in a subpopulation of R6/2 MSNs show “epileptiform” activity after the addition of the GABA_A receptor antagonist, bicuculline (10 μM) (first trace). These large-amplitude excitatory events are usually followed by high-frequency small-amplitude sEPSCs. In mice with hNSC implants these events were markedly reduced in frequency (second trace).

(F) In cells with “epileptiform” activity (6–8 min after BIC), there was a rightward shift in the cumulative inter-event interval probability distributions for the hNSC-implanted R6/2 group compared with vehicle, corresponding to a significant decrease in high-frequency spontaneous events (p < 0.001, two-way repeated-measures ANOVA followed by Bonferroni post hoc analysis; ^∗p < 0.05).