Fig. 3: Optogenetic activation of the BLA-DMS circuit induces anxiety-like behavior followed by compulsive grooming. | Nature Communications

Fig. 3: Optogenetic activation of the BLA-DMS circuit induces anxiety-like behavior followed by compulsive grooming.

From: Persistent enhancement of basolateral amygdala-dorsomedial striatum synapses causes compulsive-like behaviors in mice

Fig. 3

a Experimental scheme (ChR2BLA-DMS, n = 7; ChR2BLA-NAc, n = 8) used in (b–d, f, g). b–d Behavioral responses in EPM induced by optical stimulation of BLA-DMS. Open arm duration (b, one-way repeated measures ANOVA with Greenhouse-Geisser correction and post hoc Tukey’s test, F2.361, 14.17 = 14.86, P = 0.0002), immobility (c, two-sided Friedman test and post hoc Dunn’s multiple comparisons test, H = 23.09, P = 0.0001), and grooming duration (d, two-sided Friedman test and post hoc Dunn’s multiple comparisons test (H = 23.88, P = 8.440e−05) showed significant effects of optical stimulation. There was a significant difference between Off1 and Off3 in grooming (paired t-test, t = 9.690, df = 6, P = 6.929e−05). e Scheme (left), representative images (middle), quantification (right, n = 4 mice) of retrograde tracing of BLA-DMS and BLA-NAc projections. f Anxiety measured in EPM with BLA-DMS vs BLA-NAc activation (two-way repeated measures ANOVA with post hoc Sidak’s multiple comparisons test, interactionlight × region, F1,13 = 4.159, P = 0.0623; Light effect, F1,13 = 16.36, P = 0.0014). g Grooming behavior induced by BLA-DMS vs BLA-NAc activation (two-sided Friedman test with post hoc Dunn’s multiple comparisons test, BLA-DMS, H = 11.14, P = 0.0012; BLA-NAc, H = 1.355, P = 0.5444). h Schematic of injections in (i–m). i Representative images of anterograde transsynaptic tagging in the DMS. A subset of D1-MSNs expressing EYFP after Flpo-mediated recombination is shown in yellow. This experiment was repeated 3 times with similar results. j Inactivation of the target D1-MSNs prevented induction of excessive grooming by BLA-DMS activation (Saline, n = 6; CNO, n = 6) (Two-way repeated measures ANOVA with post hoc Sidak’s multiple comparisons test, interactionlight × drug, F4, 40 = 10.38, P = 7.324e−6). k The total distance traveled in EPM (Saline, n = 6; CNO, n = 6) (two-sided unpaired t test, t = 1.582, df = 10, P = 0.1447). l Open arm duration in EPM (Saline, n = 6; CNO, n = 6) (two-sided paired t-test, saline, t = 7.324, df = 5, P = 0.0007; CNO, t = 0.8654, df = 5, P = 0.4264). m Active climbing in FST (Saline, n = 5; CNO, n = 5) (two-way repeated measures ANOVA with post hoc Sidak’s multiple comparisons test, Drug effect, F1, 8 = 18.01, P = 0.0028).

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