Figure 5. PVVP→LHb and PVVP→VTA neurons mediate discrete symptoms of depression.
(A and B) Schematic of viral injections and optic fiber implantations for optogenetic manipulation in stressed animals.
(C and D) Representative traces of animals expressing NpHR in VP PV neurons in social interaction (SI) test in susceptible animals during light stimulation: off (left panel) and light on (589 nm; right panel). Red rectangle indicates cage in which aggressive CD1 animal was placed, yellow dashed lines outline ‘interaction zone.’ Warmer colors indicate increased time spent.
(E and F) Silencing terminals of VP PV neurons in VTA, but not in LHb, alleviates social withdrawal symptoms in SI test. SI ratio = time interaction zone light ON / light OFF. Dashed line indicates no change. Each line in (E) represents single animal, bolded line indicates average ± SEM. Mann-Whitney U-test U = 80, P < .05. (F) shows population means of data in (E). VTA SI: one-way ANOVA F2,21 = 6.132, P < .01. Tukey post-test: * P < .05; n = 5, 9, 10 and n = 6, 7, 9 animals for eYFP, ChR2, NpHR groups in VTA and LHb conditions, respectively.
(G and H) Modulation of VP PV neuronal terminals in LHb, but not in VTA induces bidirectional effects on the tail suspension test (TST). For (G), LHb-ChR2: Mann-Whitney U-test U = 56, ** P < .01; LHb-NpHR U = 15, *** P < .001. For (H), LHb TST: one-way ANOVA F2,25 = 24.49 P < .001. Tukey post-test: * P < .05; n = 5, 8, 11 and 6, 8, 14 for eYFP, ChR2, and NpHR in VTA and LHb groups, respectively. All data reported as mean ± SEM.