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bioRxiv · 10.1101/2023.07.03.547586

Purkinje cell dysfunction causes disrupted sleep in ataxic mice

Salazar Leon, L. E.·Brown, A. M.·Kaku, H.·Sillitoe, R. V.
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Abstract

Purkinje cell dysfunction causes movement disorders such as ataxia, however, recent evidence suggests that Purkinje cell dysfunction may also alter sleep regulation. Here, we used an ataxia mouse model generated by silencing Purkinje cell neurotransmission (L7Cre;Vgatfx/fx) to better understand how cerebellar dysfunction impacts sleep physiology. We focused our analysis on sleep architecture and electrocorticography (ECoG) patterns based on their relevance to extracting physiological measurements during sleep. We found that circadian activity is unaltered in the mutant mice, although their sleep parameters and ECoG patterns are modified. The L7Cre;Vgatfx/fx mutant mice have decreased wakefulness and rapid eye movement (REM) sleep, while non-rapid eye movement (NREM) sleep is increased. The mutant mice have an extended latency to REM sleep, which is also observed in human ataxia patients. Spectral analysis of ECoG signals revealed alterations in the power distribution across different frequency bands defining sleep. Therefore, Purkinje cell dysfunction may influence wakefulness and equilibrium of distinct sleep stages in ataxia. Our findings posit a connection between cerebellar dysfunction and disrupted sleep and underscore the importance of examining cerebellar circuit function in sleep disorders. Summary StatementUtilizing a precise genetic mouse model of ataxia, we provide insights into the cerebellums role in sleep regulation, highlighting its potential as a therapeutic target for motor disorders-related sleep disruptions.

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Salazar Leon, L. E., Brown, A. M., Kaku, H., Sillitoe, R. V.. 2023-07-03. Purkinje cell dysfunction causes disrupted sleep in ataxic mice. https://doi.org/10.1101/2023.07.03.547586

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