Figure 5.

Neuro-specific hippocampal AAV9 delivery in vivo restores inhibitory GABAergic signaling in acute brain slices from Ts65Dn mice

(A) Schematic representation of the experimental timeline and of the hippocampal region of acute brain slices, showing the site of electrophysiological recordings. Two-3-month-old WT and Ts65Dn mice were stereotaxically injected in the dorsal hippocampal CA1 region with AAV9 vectors and analyzed by electrophysiology 4 WPIs. (B) Percentage of spontaneously active CA1 hippocampal neurons during baseline recordings for the different experimental groups. Numbers inside the bars indicate the number of recorded cells (4–5 animals/each experimental group) that were either active or silent during baseline recordings. ∗p < 0.05, Fisher’s exact test with the Sidak adjustment for multiple comparisons. (C) Quantification of the means ± SEM spontaneous spiking activity recorded in cell-attached, patch-clamp configuration in AAV9-transduced hippocampal CA1 neurons from WT and Ts65Dn mice before and after bath application of the GABA_AR antagonist bicuculline (20 μM). (D) Example traces and spiking frequency of single, active CA1 neurons, from experiments in (C), in WT and Ts65Dn brain slices before (baseline) and during bath application of bicuculline. Numbers in parentheses indicate the number of active cells either before or after bicuculline application that were recorded for each experimental group; boxed numbers indicate the percentages of cells showing at least a 20% increase (↑) or decrease (↓) in spiking frequency after bicuculline application. ∗∗∗p < 0.001, Tukey post hoc test after two-way RMs ANOVA; ^##p < 0.01, ^###p < 0.001, Wilcoxon signed-rank test.