Figure 2. Elevated neuronal firing is reversible by FlpO-mediated restoration of Na_V1.2 expression in adult Na_V1.2-deficient mice.

(A) Cartoon illustration of mice systemically administered PHP.eB.AAV-control or PHP.eB.AAV-FlpO via tail vein injection.

(B) Coronal views of LacZ staining of the striatum from WT and Scn2a^gt/gt (HOM) mice injected with AAV-control or AAV-FlpO. Blue staining of HOM mice largely disappeared in the AAV-FlpO group. CPu, caudate nucleus and the putamen (dorsal striatum). Scale bar, 1 mm.

(C) Western blot analysis showing Na_V1.2 protein levels in whole-brain homogenates from HOM mice in the AAV-control or AAV-FlpO group. One-way ANOVA with multiple comparisons.

(D) Representative current-clamp recordings of MSNs from WT mice transduced with AAV-FlpO (red), HOM mice transduced with AAV-Control (blue), and HOM mice transduced with AAV-Control (magenta) obtained at the RMP. Inset: representative trace in response to +350 pA injection.

(E) The average number of APs generated in response to depolarizing current pulses at the RMP. Unpaired Mann-Whitney U test for each current pulse.

(F) Typical spikes of MSNs were obtained at the normal RMP.

(G) Associated phase-plane plots.

(H) Individuals and average spike rheobase. Unpaired t test.

(I) Typical spikes of MSNs at a fixed MP of −80 mV.

(J) Associated phase-plane plots at −80 mV. Data were shown as mean ± SEM.