Fig. 4: Chemogenetic activation of inhibitory PV-IN in Ambra1+/− females normalizes autistic-like dendritic spines. | Translational Psychiatry

Fig. 4: Chemogenetic activation of inhibitory PV-IN in Ambra1+/− females normalizes autistic-like dendritic spines.

From: Chemogenetic rectification of the inhibitory tone onto hippocampal neurons reverts autistic-like traits and normalizes local expression of estrogen receptors in the Ambra1+/- mouse model of female autism

Fig. 4

A Representative Golgi-stained dorsal hippocampal section. Left panel: 5x magnification, scale bar: 250 μm. Right panels: 100x magnification, scale bar: 5 μm. B Histogram reporting the mean spine density (mean ± s.e.m.): number of spines is similar in PV_Wt/Veh and PV_A/CNO females [PV_Wt/Veh (N = 6, 25 neurons), PV_A/Veh (N = 5, 25 neurons), PV_A/CNO (N = 4, 17 neurons), F(2,64)=21.63, p = 0.0001; PV_A/Veh vs PV_A/CNO, p = 0.0001; PV_Wt/Veh vs PV_A/CNO, p = 0.55]. C Spine head diameters length are expressed as cumulative frequencies (~1000 spines per group). Spine head diameters in PV_A/CNO females exceed those in PV_Wt/Veh females. (Kolmogorov Smirnoff (KS) test: PV_Wt/Veh vs PV_A/Veh, KS: D = 0.243, p < 0.001; PV_A/Veh vs PV_A/CNO, D = 0.431 p < 0.001; PV_Wt/Veh vs PV_A/CNO, D = 0.259, p < 0.001). D Upper panel: enlarged 100x magnification (scale bar: 5 μm) of a representative dendritic segment where dendritic spines types of CA1 pyramidal neurons are pointed out (mushroom spines by light blue arrows, stubby by yellow arrows and thin by dark blue arrows). Immediately below, the skeleton of the same dendritic segment with the visualization of the neck length and head diameter of each spine. Bottom square: the critical formula used for objective classification of spine-type (see methods for details). E, F Histograms reporting the percentage of thin (E) and mushroom (F) spines: percentage of thin (E) and mushroom (F) spines is similar in PV_Wt/Veh and PV_A/CNO females [PV_Wt/Veh (N = 4, neurons: 8; segments: 29), PV_A/Veh (N = 4, neurons: 8; segments: 27), PV_A/CNO (N = 4, neurons: 8; segments: 22). Thin spines: F(2,75)=16.68, p = 0.00002; PV_Wt/Veh vs PV_A/Veh, p = 0.0002; PV_A/Veh vs PV_A/CNO, p = 0.0001 = ; PV_Wt/Veh vs PV_A/CNO, p = 1; Mushroom spines: main effect Kruskal-Wallis H = 28, p = 0.0001; Dunn’s multiple comparison PV_Wt/Veh vs PV_A/Veh, p = 0.001; PV_A/Veh vs PV_A/CNO, p = 0.001]. Data are expressed as mean ± s.e.m. *p < 0.05, **p < 0.01, ***p < 0.001.

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