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Annual changes in the environment threaten survival, and numerous biological processes in mammals adjust to this challenge via seasonal encoding by the suprachiasmatic nucleus (SCN). To tune behavior according to day length, SCN neurons display unified rhythms with synchronous phasing when days are short, but will divide into two sub-clusters when days are long. The transition between SCN states is critical for maintaining behavioral responses to seasonal change, but the mechanisms regulating this form of neuroplasticity remain unclear. Here we identify that a switch in chloride transport and GABA A signaling is critical for maintaining state plasticity in the SCN network. Further, we reveal that blocking excitatory GABA A signaling locks the SCN into its long day state. Collectively, these data demonstrate that plasticity in GABA A signaling dictates how clock neurons interact to maintain environmental encoding. Further, this work highlights factors that may influence susceptibility to seasonal disorders in humans., Competing Interests: KR, HP, SH, CK, DM, NR, JE No competing interests declared, (© 2019, Rohr et al.)

Glucocorticoid production is gated at the molecular level by the circadian clock in the adrenal gland. Stress influences daily rhythms in behavior and physiology, but it remains unclear how stress affects the function of the adrenal clock itself. Here, we examine the influence of stress on adrenal clock function by tracking PERIOD2::LUCIFERASE (PER2::LUC) rhythms in vitro Relative to non-stressed controls, adrenals from stressed mice displayed marked changes in PER2::LUC rhythms. Interestingly, the effect of stress on adrenal rhythms varied by sex and the type of stress experienced in vivo To investigate the basis of sex differences in the adrenal response to stress, we next stimulated male and female adrenals in vitro with adrenocorticotropic hormone (ACTH). ACTH shifted phase and increased amplitude of adrenal PER2::LUC rhythms. Both phase and amplitude responses were larger in female adrenals than in male adrenals, an observation consistent with previously described sex differences in the physiological response to stress. Lastly, we reversed the sex difference in adrenal clock function using stress and sex hormone manipulations to test its role in driving adrenal responses to ACTH. We find that adrenal responsiveness to ACTH is inversely proportional to the amplitude of adrenal PER2::LUC rhythms. This suggests that larger ACTH responses from female adrenals may be driven by their lower amplitude molecular rhythms. Collectively, these results indicate a reciprocal relationship between stress and the adrenal clock, with stress influencing adrenal clock function and the state of the adrenal clock gating the response to stress in a sexually dimorphic manner., (© 2018 Society for Endocrinology.)