Learned helplessness assessed by active avoidance in dMHbCKO mice.

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Learned helplessness assessed by active avoidance in dMHbCKO mice. Learned helplessness assessed by active avoidance in dMHbCKO mice. A, Learned helplessness response: the mean latency to escape in the shuttle box following 1 d of inescapable shock training, or exposure to the training chamber without a shock, is shown. Both the dMHbCKO and dMHbCtrl mice that received shocks during training showed increased latency to escape, but dMHbCKO mice exhibited a stronger effect. **p < 0.01, ****p < 0.0001 for difference between groups indicated. B, Persistence of the learned helplessness response: the mean latency to escape was reassessed for the cohort shown in A 3 weeks after inescapable shock training. dMHbCtrl mice that received inescapable shocks returned to near-baseline escape times. dMHbCKO mice that received inescapable shocks retained the learned helplessness behavior. **p < 0.01 and ****p < 0.0001, significant difference between groups. N = 13 no-shock dMHbCtrl, 10 shocked dMHbCtrl, 11 no-shock dMHbCKO, and 17 shocked dMHbCKO mice. C, Convergence of learned helplessness response with extended training: the mean latency to escape was assessed after 3 d of inescapable shock training in a different cohort of mice. Both the dMHbCKO and dMHbCtrl mice received shocks during the training. The prolonged training increased escape latency for both genotypes when assessed by active avoidance 1 d after the final training session. N = 11 dMHbCtrl and 9 dMHbCKO mice. D, E, Assessment of learned helplessness in a separate cohort of Pou4f1 hemizygous mice. D, Learned helplessness response: the mean latency to escape in the shuttle box following 1 d of inescapable shock training is shown. Both the Pou4f1+/- and Pou4f1+/+ (wild-type) mice received shocks during the training. Pou4f1+/- mice exhibited increased latency to escape relative to Pou4f1+/+ mice, i.e., were more susceptible to the induction of learned helplessness. **p = 0.0059, significant difference between the genotypes. E, Persistence of learned helplessness response: the mean latency to escape was reassessed for the cohort shown in D 3 weeks after inescapable shock training. The Pou4f1+/- mice showed persistently elevated escape latency relative to Pou4f1+/+ mice. ***p = 0.0007, significant difference between the genotypes. Minor modifications to the active avoidance protocol used in D and E, resulting in somewhat longer escape times, are described in Materials and Methods. Yun-Wei A. Hsu et al. eneuro 2016;3:ENEURO.0109-16.2016 ©2016 by Society for Neuroscience