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bioRxiv · 10.1101/2023.09.11.557218

A brain circuit and neuronal mechanism for decoding and adapting to change in daylength

Maddaloni, G.·Chang, Y.·Senft, R. A.·Dymecki, S. M.
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Abstract

Changes in daylight amount (photoperiod) drive pronounced alterations in physiology and behaviour1,2. Adaptive responses to seasonal photoperiods are vital to all organisms - dysregulation is associated with disease, from affective disorders3 to metabolic syndromes4. Circadian rhythm circuitry has been implicated5,6 yet little is known about the precise neural and cellular substrates that underlie phase synchronization to photoperiod change. Here we present a previously unknown brain circuit and novel system of axon branch-specific and reversible neurotransmitter deployment that together prove critical for behavioural and sleep adaptation to photoperiod change. We found that the recently defined neuron type called mrEn1-Pet17 located in the mouse brainstem Median Raphe Nucleus (MRN) segregates serotonin versus VGLUT3 (here proxy for the neurotransmitter glutamate) to different axonal branches innervating specific brain regions involved in circadian rhythm and sleep/wake timing8,9. We found that whether measured during the light or dark phase of the day this branch-specific neurotransmitter deployment in mrEn1-Pet1 neurons was indistinguishable; however, it strikingly reorganizes on photoperiod change. Specifically, axonal boutons but not cell soma show a shift in neurochemical phenotype upon change away from equinox light/dark conditions that reverses upon return to equinox. When we genetically disabled the deployment of VGLUT3 in mrEn1-Pet1 neurons, we found that sleep/wake periods and voluntary activity failed to synchronize to the new photoperiod or was significantly delayed. Combining intersectional rabies virus tracing and projection-specific neuronal silencing in vivo, we delineated a Preoptic Area-to-mrEn1Pet1 connection responsible for decoding the photoperiodic inputs, driving the neurochemical shift and promoting behavioural synchronization. Our results reveal a previously unrecognized brain circuit along with a novel form of periodic, branch-specific neurotransmitter deployment that together regulate organismal adaptation to photoperiod changes.

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Maddaloni, G., Chang, Y., Senft, R. A., Dymecki, S. M.. 2023-09-13. A brain circuit and neuronal mechanism for decoding and adapting to change in daylength. https://doi.org/10.1101/2023.09.11.557218

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