Purkinje Cell Dysfunction Causes Disrupted Sleep in Ataxic Mice

Authors

Luis E Salazar Leon
Amanda M Brown
Heet Kaku
Roy V Sillitoe

Publication Date

6-1-2024

Journal

Disease Models & Mechanisms

DOI

10.1242/dmm.050379

PMID

38563553

PMCID

PMC11190574

PubMedCentral® Posted Date

6-12-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Animals, Purkinje Cells, Wakefulness, Ataxia, Sleep, Sleep, REM, Mice, Circadian Rhythm, Disease Models, Animal, Male

Abstract

Purkinje cell dysfunction disrupts movement and causes disorders such as ataxia. Recent evidence suggests that Purkinje cell dysfunction may also alter sleep regulation. Here, we used an ataxic 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 was unaltered in the mutant mice, although their sleep parameters and ECoG patterns were modified. The L7Cre;Vgatfx/fx mutant mice had decreased wakefulness and rapid eye movement (REM) sleep, whereas non-REM sleep was increased. The mutants had an extended latency to REM sleep, which is also observed in human patients with ataxia. 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.