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. 2014 May 28;34(22):7485–7492. doi: 10.1523/JNEUROSCI.5294-13.2014

Figure 4.

Figure 4.

Chemical–genetic activation of mPFC neurons in ROSA-stopflox-TRPV1; TRPV1−/− mice converts resilience to helplessness-like behavior. A, Representative image of the mPFC of a ROSA-stopflox-TRPV1;TRPV1−/− mouse with bilateral injections of AAV-GFP-IRES-Cre to activate TRPV expression. B, Capsaicin treatment (20 mg/kg, i.p.) of the injected mice markedly increased both the number of failures and escape latency in the learned helplessness testing session. These behavioral parameters for each mouse are represented by a pair of circles, with the black and red circles indicating parameters measured in the absence and presence, respectively, of capsaicin treatment. Dashed line connects circles representing the same mouse. Compared with the black circles, the red circles are closer to the LH centroid (red star, reproduced from Fig. 1A for visual inspection). C, Behavioral effect of capsaicin treatment, quantified as the squared M-distance to the LH centroid (Fig. 1A; see Materials and Methods), was dose-dependent and reversible. The same mice were tested for learned helplessness at 5 min after each of the capsaicin treatment at the indicated dose, and also at 1 h for 20 mg/kg only. D, Chemical–genetic activation of mPFC neurons does not affect motor activity in an open field test. The “TRPV1” mice are the same ROSA-stopflox-TRPV1;TRPV1−/− mice (in which the mPFC were injected with AAV-GFP-IRES-Cre) used in B and C. The “Control” mice are ROSA-stopflox-TRPV1;TRPV1−/− mice without viral injection. At 5 min after treatment with capsaicin, mice were tested in an open field test. The total distance traveled (left), distance traveled in the center (middle), and velocity in the center (right) of the arena were measured. Activation of mPFC neurons by capsaicin did not significantly affect these parameters. E, Resilient mice were repeatedly tested in the learned helplessness testing sessions, with a 2 d intersession interval. Behavioral responses are quantified as in C. The resilient behavior did not change with repeated testing. ***p < 0.001.