Abstract
Drinking behavior and osmotic regulatory mechanisms exhibit clear daily variation which is necessary for achieving the homeostatic osmolality. In mammals, the master clock in the brain's suprachiasmatic nuclei has long been held as the main driver of circadian (24 h) rhythms in physiology and behavior. However, rhythmic clock gene expression in other brain sites raises the possibility of local circadian control of neural activity and function. The subfornical organ (SFO) and the organum vasculosum laminae terminalis (OVLT) are two sensory circumventricular organs (sCVOs) that play key roles in the central control of thirst and water homeostasis, but the extent to which they are subject to intrinsic circadian control remains undefined. Using a combination of ex vivo bioluminescence and in vivo gene expression, we report for the first time that the SFO contains an unexpectedly robust autonomous clock with unusual spatiotemporal characteristics in core and noncore clock gene expression. Furthermore, putative single‐cell oscillators in the SFO and OVLT are strongly rhythmic and require action potential‐dependent communication to maintain synchrony. Our results reveal that these thirst‐controlling sCVOs possess intrinsic circadian timekeeping properties and raise the possibility that these contribute to daily regulation of drinking behavior.
Highlights
Robust daily rhythms of physiology and behavior are crucial for optimal health and well-being.[1,2,3] In mammals, intrinsic near 24 hours or circadian rhythms are driven by the master clock in the brain's suprachiasmatic nuclei (SCN)
We provide the first description of a robust circadian clock in the subfornical organ (SFO) and compare its single-cell oscillator properties to those of cells in the organum vasculosum laminae terminalis (OVLT) and the SCN
We discovered that 8 out of 16 circadian clock gene transcripts involved in the transcriptional-translational feedback loop (TTFL)[31] showed significant variation over time
Summary
Robust daily rhythms of physiology and behavior are crucial for optimal health and well-being.[1,2,3] In mammals, intrinsic near 24 hours or circadian rhythms are driven by the master clock in the brain's suprachiasmatic nuclei (SCN). Rhythmic core clock gene expression occurs in the brain areas outside of the SCN, such as the olfactory bulb, mediobasal hypothalamus and the habenula, raising the possibility that circadian control of neural function is locally devolved.[7,8,9,10,11,12,13] The generation of animals bearing clock gene reporter constructs, in particular the PERIOD2::LUCIFERASE (PER2::LUC) mouse, has enabled the real-time visualization of clock gene oscillations ex vivo to study tissue-level spatiotemporal dynamics as well as the behavior of single-cell oscillators and their interactions.[14,15] Importantly, visualization of bioluminescence signals allows the investigation of potential timekeeping in smaller brain areas that would otherwise be undetectable using nonimage-based luminometry. Our results show the SFO and OVLT to possess the intrinsic timekeeping capabilities at whole tissue and individual cellular level
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