Fig. 3: Shank3 KO mice showed reduced activation in neurons controlling orienting response. | Molecular Psychiatry

Fig. 3: Shank3 KO mice showed reduced activation in neurons controlling orienting response.

From: Translational research approach to social orienting deficits in autism: the role of superior colliculus-ventral tegmental pathway

Fig. 3: Shank3 KO mice showed reduced activation in neurons controlling orienting response.

a Schema reporting the viral injections (AAVrg-Ef1α-mCherry-IRES-Cre in the VTA and AAV-hSyn1-dlox-jGCaMP7f(rev)-dlox-WPRE in the SC) and the GRIN lens implantation above the SC. b Right panel: schema of the free social interaction test. Left panel: example traces of calcium signals recordings (z-score) from SC-VTA-projecting neurons during the free social interaction test. c Intrinsic parameters of the calcium transients recorded in Shank3+/+ (in blue, 119 neurons from 9 mice) and Shank3−/− (in orange, 118 neurons from 9 mice): frequency (Mann-Whitney test: p-value < 0.001), decay time (Mann-Whitney test: p-value = 0.04), and amplitude (Mann-Whitney test: p-value = 0.85). d interneuronal correlation. Left panel: example of estimation of partial correlation networks using EBIC selection (hyperparameter = 0.5). Right panel: violin plots reporting the percentage of significant correlations for a neuron in Shank3+/+ (in blue, 119 neurons from 9 mice) and Shank3−/− (in orange, 118 neurons from 9 mice) brains during habituation phase (Mann-Whitney test: p-value < 0.001) and interaction with a juvenile (Mann-Whitney test: p-value < 0.001). e Neural responses to social orientation. Heatmaps reporting the peri-event time histogram (PETH) of normalized calcium signals (mean z-score) for SC-VTA-projecting neurons in Shank3+/+ (in blue, 119 neurons from 9 mice) and Shank3−/− (in orange, 118 neurons from 9 mice) centered on ipsi- and contra-recorded orientations. f AUC (periods [−2:0] and [0:2]) calculated from the mean z-score reported in e per Shank3+/+ and Shank3−/− neurons (two-way ANOVA with Bonferroni post-hoc comparison. Ipsi: genotype main effect F(1, 235) = 2.580, p  =  0.109, period main effect F(1, 235) = 21.34, p  < 0.001, genotype x period interaction F(1, 235) = 23.19, p  < 0.001. Contra: genotype main effect F(1, 235) = 0.7460, p  =  0.389, period main effect F(1, 235) = 8.489, p  = 0.004, genotype x period interaction F(1, 235) = 0.09, p  = 0.764). g Barplot reporting the percentage of responding neurons according to the increase of AUC (AUC[0; 2] - AUC[−2; 0]) per Shank3+/+ and Shank3−/− group. Violin plots are reporting the mean +/− s.e.m. as error bars.

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