Fig. 7.

Chronic reactivation of the BLA-NAc circuit responding to positive experience rescues attenuated reward sensitivity induced by chronic restraint stress.

(A) Diagram illustrating virus injection and implanting cannula in target areas and subsequent experiments. (B) Chronic reactivation of projections from BLA to NAc specially activated during positive experience by infusion of CNO into NAc increased sucrose preference under chronic stress condition. Left, water consumption (Mann-Whitney Utest, P = 0.3531); Middle, sucrose consumption (two-tailed unpaired t-test, t₍₂₀₎ = 3.451, P = 0.0025); Right, sucrose preference (wo-tailed unpaired t-test, t₍₂₀₎ = 4.624, P = 0.0002). Chronic reactivation of projections from BLA to NAc specially activated during positive experience increased female urine sniff time (C, two-tailed unpaired t-test, t₍₂₀₎ = 5.117, P < 0.0001), but did not influence the locomotor activity between two groups (D, two-tailed unpaired t-test, t₍₂₁₎ = 1.353, P = 0.1911), under chronic stress condition. Neutral experience group n = 10, positive experience group n = 12 in SPT (B), FUST (C), and locomotor (D). (E) Diagram illustrating virus injection and implanting cannula in target areas and subsequent experiments. Blockade of the projections from BLA to NAc responding to positive experience by CNO infusion increased the number of spontaneously active GABAergic neurons per track in the VTA (F, two-tailed unpaired t-test, t₍₁₄₎ = 2.616, P = 0.0203; mCherry n = 8 mice (37 neurons), hM4D n = 8 mice (50 neurons)), didn't influence the firing rate (G, two-tailed unpaired t-test with Welch's correction, t_(8.766) = 1.004, P = 0.3423: mCherry n = 8 mice (37 neurons), hM4D n = 8 mice (50 neurons)), while decreased the number of spontaneously active the dopaminergic neurons per track in the VTA (H, Mann-Whitney U test, P = 0.0023; mCherry n = 6 mice (40 neurons), hM4D n = 7 mice (24 neurons)) and no change in the firing rate (I, two-tailed unpaired t-test, t₍₁₁₎ = 0.2173, P = 0.8320; mCherry n = 6 mice (40 neurons), hM4D n = 7 mice (24 neurons)) and the percentage of burst firing (J, two-tailed unpaired t-test, t₍₁₁₎ = 0.6126, P = 0.5526; mCherry n = 6 mice (40 neurons), hM4D n = 7 mice (24 neurons)). (K) Diagram illustrating virus injection and implanting cannula in target areas and subsequent experiments. Reactivation of the projections from BLA to NAc responding to positive experience by CNO infusion decreased the number of spontaneously active GABAergic neurons per track in the VTA (L, two-tailed unpaired t-test, t₍₁₆₎ = 2.146, P = 0.0476; mCherry n = 8 mice (39 neurons), hM3D n = 10 mice (36 neurons)), didn't influence the firing rate (M, two-tailed unpaired t-test, t₍₁₆₎ = 0.02529, P = 0.9801: mCherry n = 8 mice (39 neurons), hM3D n = 10 mice (36 neurons)), while increased the number of spontaneously active the dopaminergic neurons per track in the VTA (N, two-tailed unpaired t-test, t₍₁₃₎ = 2.386, P = 0.0330: mCherry n = 7 mice (46 neurons), hM3D n = 8 mice (68 neurons)) and no change in the firing rate (O, two-tailed unpaired t-test, t₍₁₃₎ = 0.1097, P = 0.9143; mCherry n = 7 mice (46 neurons), hM3D n = 8 mice (68 neurons)) and the percentage of burst firing (P, Mann-Whitney U test, P = 0.5358; mCherry n = 7 mice (46 neurons), hM3D n = 8 mice (68 neurons)). *P < 0.05, **P < 0.01, ***P < 0.001. Data are presented as means±SEM.