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. 2025 Jan 8;13:RP98661. doi: 10.7554/eLife.98661

Figure 6. AAV-mediated expression of FGF13 isoforms rescues excitability deficits in Gad2-Fgf13 cKO neurons.

Figure 6.

(A) Examples of FGF13-stained neurons from primary hippocampal neuron cultures generated from Gad2-Fgf13 cKO male mice transduced with AAV8-DIO-GFP only, AAV8-DIO-GFP and AAV8-DIO-Fgf13-S, or AAV8-DIO-GFP and AAV8-DIO-Fgf13-VY (scale bar, 20 μm). (B) Gad2-Fgf13 cKO neurons expressing FGF13-VY or FGF13-S were not different in terms of threshold potential or rheobase, and were not different from wildtype (black line, from Figure 5) and Gad2-Fgf13 cKO neurons (red line, from Figure 5) (t-test, p=ns, KO +VY N=3, n=14; KO +S N=3 n=17). (C) Evoked action potential traces from Gad2-Fgf13 cKO interneurons expressing FGF13-VY or FGF13-S. Input-output curve shows increased firing of evoked action potentials from the FGF13-VY or FGF13-S expressing interneurons, relative to Gad2-Fgf13 cKO interneurons (red line, from Figure 5; black line = wild type, from Figure 5) (two-way ANOVA, *, p<0.05). (D) Gad2-Fgf13 cKO interneurons expressing FGF13-VY and FGF13-S do not enter depolarization block as early as Gad2-Fgf13 cKO interneurons (Red line [Gad2-Fgf13 cKO] and black line [wild type] are from Figure 5) (log-rank test, *, p<0.05). (E) Action potential wave forms and phase plots for the initial three action potentials of the spike train for FGF13-VY and FGF13-S rescued Gad2-Fgf13 cKO interneurons. The black and red lines are from Figure 5. (F) For the first three action potentials in the spike train, Gad2-Fgf13 cKO neurons re-expressed with FGF13-VY show no difference from Gad2-Fgf13 cKO neurons in terms of dV/dt max, AP peak, and AP amplitude, and AP50. Gad2-Fgf13 cKO neurons re-expressed with FGF13-S show difference from Gad2-Fgf13 cKO neurons only for the first action potential for AP peak and AP amplitude, but not dV/dt max or AP50. (two-way ANOVA, ***, p<0.001, KO +S vs. KO; **, p<0.01, KO +S vs. KO). (G) FGF13-S rescued neurons show a significant decrease in membrane voltage from Gad2-Fgf13 cKO neurons by the third action potential in the spike train (two-way ANOVA, *, p<0.05, KO +S vs. KO). (H) Example traces of K+ currents from Gad2-Fgf13 cKO neurons expressing FGF13-VY and FGF13-S. K+ currents are rescued by expression of FGF13-S in Gad2-Fgf13 cKO interneurons (two-way ANOVA, *, p<0.05, KO +VY N=5, n=21, KO +S N=5, n=21).