Fig. 4: Chemogenetic and optogenetic manipulation of vSub D1 and D2 neurons during EPM testing.
a, Experimental schematic. Male D1-Cre and D2-Cre mice were injected in vSub with an AAV-DIO-hM3Dq (n = 8 D1, n = 12 D2) or a control AAV-DIO-mCherry (n = 12 D1, n = 11 D2). CNO (3 mg/kg) was administered i.p. to all animals 15 min before testing. b, Representative examples of EPM exploration from D1-Cre mice (left) and quantification of open arm (OA) exploration time (right). Welch’s t-test: t14.86 = 2.1775 p = 0.0460. c, Representative examples of EPM exploration from D2-Cre mice (left) and quantification of open arm exploration time (right). Welch’s t-test: t16.65 = −2.8063 p = 0.0123. d, Experimental schematic. Male D1-Cre and D2-Cre mice were injected in vSub with an AAV-DIO-hM4Di (n = 11 D1, n = 12 D2) or a control AAV-DIO-mCherry (n = 12 D1, n = 12 D2). CNO (3 mg/kg) was administered i.p. to all animals 15 min before testing. e, Representative examples of EPM exploration from D1-Cre mice (left) and quantification of open arm exploration time (right). Welch’s t-test: t16.97 = −0.967 p = 0.3471. f, Representative examples of EPM exploration from D2-Cre mice (left) and quantification of open arm exploration time (right). Welch’s t-test: t21.43 = 2.5307 p = 0.0193. g, Experimental schematic. Male D1-Cre and D2-Cre mice were injected in vSub with an AAV-DIO-ChR2 (n = 9 D1, n = 10 D2) or a control AAV-DIO-EYFP (n = 10 D1, n = 11 D2). Optogenetic stimulation (473 nm laser, 8 mW, 20 Hz, 10 ms pulses) was delivered when the animal was either in the center or open arm (Ce+OA) or in the center and closed arm (Ce+CA) in a within-subject design. h, Representative examples of EPM exploration from D1-Cre mice (left) and quantification of open arm exploration time (right). LMM-ANOVA: stimulation zone F1,17 = 6.21 p = 0.0233, virus F1,17 = 0.26 p = 0.6145, stimulation zone x virus F1,17 = 6.72 p = 0.0190; followed by FDR-adjusted post-hoc tests. i, Representative examples of EPM exploration from D2-Cre mice (left) and quantification of open arm exploration time (right). LMM-ANOVA: stimulation zone F1,19 = 9.34 p = 0.0065, virus F1,19 = 8.96 p = 0.0075, stimulation zone x virus F1,19 = 7.68 p = 0.0121; followed by FDR-adjusted post-hoc tests. Data represented as mean ± sem.