Fig. 3: Activity dependent regulation of aberrant neurogenesis is restricted to an early critical period. | Nature Communications

Fig. 3: Activity dependent regulation of aberrant neurogenesis is restricted to an early critical period.

From: A critical period of neuronal activity results in aberrant neurogenesis rewiring hippocampal circuitry in a mouse model of epilepsy

Fig. 3: Activity dependent regulation of aberrant neurogenesis is restricted to an early critical period.

a Mice were injected with retrovirus to express hM3Dq (green) or CAG-GFP (gray) in neural stem cells. Eight weeks following injections, mice were implanted for video-EEG and recorded for seizures. One week of baseline was recorded and then either saline (Veh) or CNO was injected daily. b Representative images. c Quantification of migration distance. d Sholl analysis of dendrite complexity from GFP group (e) and hM3Dq group. For c–e, n = 110 (hM3Dq + Veh:gray), 55 (hM3Dq + CNO;green), 124 (GFP + Veh:green), 143(GFP + CNO:gray) cells per group. Ten mice per group. f There was no difference in dendrite angle in GFP. g Cumulative distribution of the primary dendrite angle of GFP angle. *p < 0.01, Kolmogorov–Smirnov test. h There was no difference in dendrite angle in hM3Dq. i Cumulative distribution of hM4Di group. j Table of spontaneous seizures with each group reporting baseline and percentage of responses to CNO. *p < 0.05, Chi-squared test. k Experimental design for silencing mature aberrant abGCs. Following retrovirus delivery of DREADDs or control GFP, and pilo-induced SE, EEG recording was performed at day 42 to collect baseline data. At day 43 post SE, CNO was administered and the acute effects were monitored for 24 h. l Quantification of the change in SRS from baseline. m Quantification of the change in spike activity from baseline. n Quantification of the frequency and o duration of spontaneous seizures. For l–r, n = 11 (GFP + CNO), 9 (hM4Di + CNO) mice per group. p Experimental design for the chronic effect of silencing aberrant mature neurons. Six weeks following SE, mice were EEG monitored while receiving CNO administration. q Silencing mature aberrant abGCs does not alter dendrite morphology in GFP group or r hM4Di group. For q, r, n = 58 (GFP + Veh; gray), 63(GFP + CNO; gray), 44(hM4Di + CNO;green), 16 (hM4DI + Veh;green) cells per group. *p < 0.05, ANOVA with multiple comparisons. All statistics calculated using two-tailed test.

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