Fig. 3: Chemogenetic inhibition of CA1 principal neuron activity in Ambra1+/− females rescues autistic-like behaviors. | Translational Psychiatry

Fig. 3: Chemogenetic inhibition of CA1 principal neuron activity in Ambra1+/− females rescues autistic-like behaviors.

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. 3

A Breeding. B Representative images of NeuroTrace/CamKII/mCherry labelling showing overlapping signals (yellow) of mCherry (red) and CamKII- neurons (green). hM4Di receptors are selectively expressed in CA1 principal neurons. Scale bars: top, 200 μm; below, 50 μm. C Experimental design: the inhibitory rAAV5/CaMKIIa-hM4D(Gi)-mCherry vector was bilaterally injected in CA1 of Wt and Ambra1+/− females. Behavioral tests were performed 4 weeks later. Vehicle (Veh) or CNO were injected i.p. 40 min before testing. D Histogram reporting mean time spent exploring the object (Obj) and the conspecific stranger (S1) during the sociability phase of the TC test. All mice explore more the conspecific stranger than the object (Wt/Veh: Obj vs S1: t(8)=5.43, p = 0.0006; A/Veh: Obj vs S1: t(7)=7.389, p = 0.0002; A/CNO: Obj vs S1: t(7)=5.531, p = 0.0009). E Histogram reports mean time spent exploring the familiar female (S1) and the novel female (S2) during the social novelty phase of the TC test. Only A/Veh females show impairment in recognition of the social novelty as they spent equal amount of time sniffing S1 and S2. (Wt/Veh: S1 vs S2: t(8)=2.517, p = 0.036; A/Veh: S1 vs S2: t(7)=0.562, p = 0.59; A/CNO: S1 vs S2: t(7)=5.251, p = 0.001). F Histogram reporting the mean recognition index (RI) calculated during the social novelty phase of TC. Social novelty impairments in A/Veh females are rescued in A/CNO females. (TC social novelty phase: Wt/Veh (N = 9), A/Veh (N = 8) and A/CNO (N = 8); Kruskal-Wallis H = 12.01, p = 0.002; Dunn’s multiple comparison Wt/Veh vs A/Veh, p = 0.029; A/Veh vs A/CNO, p = 0.005). G Histogram reports mean time spent exploring the two identical objects during the object exploration phase of the NOR test by Wt and A females injected with Veh or CNO. Data indicate that regardless of genotype and treatment all mice similarly explore the identical objects (Obj1 vs ObjI: Wt/Veh: W = -9, p = 0.63; A/Veh: W = -17, p = 0.17; A/CNO: t(6)=0.98, p = 0.36). H Histogram reports mean time spent exploring the familiar object (ObjF) and the novel object (ObjN) during the test phase of the NOR by Wt/Veh females and A females injected with Veh or CNO. Data indicate that recognition impairments of the novel object in A/Veh females are rescued in A/CNO females (ObjF vs ObjN: Wt/Veh: W = 45, p = 0.0039; A/Veh: W = 12, p = 0.37; A/CNO: W = -26, p = 0.031). I Histogram reporting the mean recognition index (RI) calculated during the test phase of NOR test. Novel object recognition impairments in A/Veh females are rescued in A/CNO females (Wt/Veh (N = 9), A/Veh (N = 7), and A/CNO (N = 7); F(2,20)=7.473, p = 0.0038; Wt/Veh vs A/Veh p = 0.004 A/Veh vs A/CNO, p = 0.021). Data are expressed as mean ± s.e.m. *p < 0.05, **p < 0.01, ***p < 0.001.

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