Fig. 2: Chemogenetic activation of inhibitory PV-IN in Ambra1^+/− females normalizes autistic-like behaviors.

A Histogram report 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 (PV_Wt/Veh: Obj vs S1: t₍₁₆₎=7.116, p = 0.0001; PV_A/Veh: Obj vs S1: t₍₁₃₎=7.714, p = 0.0001; PV_A/CNO: Obj vs S1: t₍₁₀₎=5.507, p = 0.0003; Dotted-line indicate mean values detected in PV_Wt/CNO control mice infused with vehicle instead of DREADDs. B Histogram report mean-time spent exploring the familiar female (S1) and the novel female (S2) during the social novelty phase of the TC test. Only PV_A/Veh females show impairment in recognition of the social novelty as they spent equal amounts of time sniffing S1 and S2. (PV_Wt/Veh: S1 vs S2: W = 119, p = 0.0032; PV_A/Veh: S1 vs S2: t₍₁₃₎=1.740, p = 0.1; PV_A/CNO: S1 vs S2: W = 55, p = 0.002). Dotted-line indicate mean values detected in PV_Wt/CNO control mice infused with vehicle instead of DREADDs. C 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: PV_Wt/Veh (N = 17), PV_A/Veh, (N = 14), PV_A/CNO (N = 11), F_(2,39)=11.26 p = 0.0001; PV_Wt/Veh vs PV_A/Veh, p = 0.00086; PV_A/Veh vs PV_A/CNO, p = 0.037. Dotted-line indicate mean values detected in PV_Wt/CNO control mice infused with vehicle instead of DREADDs. D Histogram reports mean time spent exploring an unknown conspecific during the social interaction in pair test (SIP). Social interaction impairments of PV_A/Veh females in SIP test are rescued in PV_A/CNO females (SIP: PV_Wt/Veh (N = 8), PV_A/Veh (N = 8), PV_A/CNO (N = 9), F_(2,22)=6.186, p = 0.007; PV_Wt/Veh vs PV_A/Veh, p = 0.009; PV_A/Veh vs PV_A/CNO, p = 0.04). E Histogram report mean time spent exploring the two identical objects (Object 1 (Obj1) and Identical Object (Obj I)) during the object exploration phase of the NOR test by PV_Wt/Veh females and PV_A females injected with Veh or CNO. Data indicate that regardless of genotype and treatment all mice similarly explore the identical objects (PV_Wt/Veh: Obj1 vs ObjI: W = 7, p = 0.88; PV_A/Veh: Obj1 vs ObjI: W = -38, p = 0.24; PV_A/CNO: Obj1 vs ObjI: t₍₁₂₎=1.102, p = 0.29). Dotted-line indicate mean values detected in PV_Wt/CNO control mice infused with vehicle instead of DREADDs. F Histogram report mean time spent exploring the familiar object (ObjF) and the novel object (Obj N) during the test phase of the NOR by PV_Wt/Veh females and PV_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: PV_Wt/Veh: t₍₁₆₎=7.06, p = 0.0001; PV_A/Veh: W = -29, p = 0.38; PV_A/CNO: W = -91, p = 0.0002). Dotted-line indicate mean values detected in PV_Wt/CNO control mice infused with vehicle instead of DREADDs. G Histogram reporting the mean recognition index (RI) calculated during the test phase of NOR test. Novel object recognition impairments in PV_A/Veh females are rescued in PV_A/CNO females. (PV_Wt/Veh (N = 17), PV_A/Veh (N = 14), PV_A/CNO (N = 13), F_(2,41)=6.59, p = 0.003; PV_Wt/Veh vs PV_A/Veh, p = 0.023; PV_A/Veh vs PV_CNO, p = 0.004). Dotted-line indicate mean values detected in PV_Wt/CNO control mice infused with vehicle instead of DREADDs. Data are expressed as mean ± s.e.m. *p < 0.05, **p < 0.01, ***p < 0.001.