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bioRxiv · 10.1101/2025.01.21.634103

Perinatal circadian desynchronization disrupts sleep and prefrontal cortex function in adult offspring

Roberts, B. L.·Wang, J.·Chargui, H.·Cupertino, N. C.·Sorensen, W.·Karatsoreos, I. N.
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Abstract

Sleep and circadian (daily) rhythms impact nearly all aspects of physiology and are critical for optimal organismal function. Disruption of the clock can lead to significant metabolic disorders, neuropsychiatric illness, and cognitive dysfunction. Our lab has previously shown that environmental circadian desynchronization (ECD) in adults alters the anatomical structure and neurophysiological function of prefrontal cortex (PFC) neurons, PFC mediated behaviors, as well as sleep quality. As the PFC undergoes significant development in utero and early life, and maternal disturbances during this period can have significant long-term ramifications, we hypothesized that disrupting the circadian environment of dams during the perinatal period would alter sleep and PFC function in adult offspring. Using a mouse model of ECD we investigated how perinatal ECD (pECD) modulates sleep quality in adult offspring. We also determined how pECD impacts PFC neural function in adult offspring using ex vivo patch-clamp electrophysiology, exploring how pECD alters synaptic function and action potential dynamics. We found that male pECD mice trended toward increased total sleep during the inactive (light) period with shorter sleep bouts during the active (dark) period. pECD did not change sleep behavior in female mice. Independent of time of day, pECD altered post-synaptic dynamics of excitatory neurotransmitter release onto plPFC pyramidal neurons. There was also a loss of time-of-day effects on cell endogenous properties in male pECD mice. Thus, pECD clearly alters sleep behavior and PFC function in male mice. However, female mice appear protected against the effects of pECD in these measures. Together, these experiments form the foundation for future studies to understand the lifelong neurobehavioral impact of pECD.

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Roberts, B. L., Wang, J., Chargui, H., Cupertino, N. C., Sorensen, W., Karatsoreos, I. N.. 2025-01-22. Perinatal circadian desynchronization disrupts sleep and prefrontal cortex function in adult offspring. https://doi.org/10.1101/2025.01.21.634103

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