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Background/Aims: Circadian rhythms in behavior and physiology are programmed by the suprachiasmatic nucleus (SCN) of the hypothalamus. A subset of SCN neurons produce the neuropeptide arginine vasopressin (AVP), but it remains unclear whether AVP signaling influences the SCN clock directly. Methods: Here, we test that AVP signaling acting through V1A and V1B receptors influences molecular rhythms in SCN neurons. V1 receptor agonists were applied ex vivo to PERIOD2::LUCIFERASE SCN slices, allowing for real-time monitoring of changes in molecular clock function. Results: V1A/B agonists reset the phase of the SCN molecular clock in a time-dependent manner, with larger magnitude responses by the female SCN. Further, we found evidence that both Gαq and Gαs signaling pathways interact with V1A/B-induced SCN resetting, and that this response requires vasoactive intestinal polypeptide (VIP) signaling. Conclusions: Collectively, this work indicates that AVP signaling resets SCN molecular rhythms in conjunction with VIP signaling and in a manner influenced by sex. This highlights the utility of studying clock function in both sexes and suggests that signal integration in central clock circuits regulates emergent properties important for the control of daily rhythms in behavior and physiology. [ABSTRACT FROM AUTHOR]

Daily rhythms are generated by the circadian timekeeping system, which is orchestrated by the master circadian clock in the suprachiasmatic nucleus (SCN) of mammals. Circadian timekeeping is endogenous and does not require exposure to external cues during development. Nevertheless, the circadian system is not fully formed at birth in many mammalian species and it is important to understand how SCN development can affect the function of the circadian system in adulthood. The purpose of the current review is to discuss the ontogeny of cellular and circuit function in the SCN, with a focus on work performed in model rodent species (i.e., mouse, rat, and hamster). Particular emphasis is placed on the spatial and temporal patterns of SCN development that may contribute to the function of the master clock during adulthood. Additional work aimed at decoding the mechanisms that guide circadian development is expected to provide a solid foundation upon which to better understand the sources and factors contributing to aberrant maturation of clock function. [ABSTRACT FROM AUTHOR]

Norepinephrine exerts powerful influences on the metabolic, neuroprotective and immunoregulatory functions of astrocytes. Until recently, all effects of norepinephrine were believed to be mediated by receptors localized exclusively to the plasma membrane. However, recent studies in cardiomyocytes have identified adrenergic receptors localized to intracellular membranes, including Golgi and inner nuclear membranes, and have shown that norepinephrine can access these receptors via transporter-mediated uptake. We recently identified a high-capacity norepinephrine transporter, organic cation transporter 3 (OCT3), densely localized to outer nuclear membranes in astrocytes, suggesting that adrenergic signaling may also occur at the inner nuclear membrane in these cells. Here, we used immunofluorescence and western blot to show that β 1 -adrenergic receptors are localized to astrocyte inner nuclear membranes; that key adrenergic signaling partners are present in astrocyte nuclei; and that OCT3 and other catecholamine transporters are localized to astrocyte plasma and nuclear membranes. To test the functionality of nuclear membrane β 1 -adrenergic receptors, we monitored real-time protein kinase A (PKA) activity in astrocyte nuclei using a fluorescent biosensor. Treatment of astrocytes with norepinephrine induced rapid increases in PKA activity in the nuclear compartment. Pretreatment of astrocytes with inhibitors of catecholamine uptake blocked rapid norepinephrine-induced increases in nuclear PKA activity. These studies, the first to document functional adrenergic receptors at the nuclear membrane in any central nervous system cell, reveal a novel mechanism by which norepinephrine may directly influence nuclear processes. This mechanism may contribute to previously described neuroprotective, metabolic and immunoregulatory actions of norepinephrine., (© 2022 Wiley Periodicals LLC.)

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.)