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Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9974-9. doi: 10.1073/pnas.1221381110. Epub 2013 May 28.

Neuroligin-1 links neuronal activity to sleep-wake regulation.

Author information

1
Department of Psychiatry, Université de Montréal, Montreal, QC, Canada H3C 3J7.

Abstract

Maintaining wakefulness is associated with a progressive increase in the need for sleep. This phenomenon has been linked to changes in synaptic function. The synaptic adhesion molecule Neuroligin-1 (NLG1) controls the activity and synaptic localization of N-methyl-d-aspartate receptors, which activity is impaired by prolonged wakefulness. We here highlight that this pathway may underlie both the adverse effects of sleep loss on cognition and the subsequent changes in cortical synchrony. We found that the expression of specific Nlg1 transcript variants is changed by sleep deprivation in three mouse strains. These observations were associated with strain-specific changes in synaptic NLG1 protein content. Importantly, we showed that Nlg1 knockout mice are not able to sustain wakefulness and spend more time in nonrapid eye movement sleep than wild-type mice. These changes occurred with modifications in waking quality as exemplified by low theta/alpha activity during wakefulness and poor preference for social novelty, as well as altered delta synchrony during sleep. Finally, we identified a transcriptional pathway that could underlie the sleep/wake-dependent changes in Nlg1 expression and that involves clock transcription factors. We thus suggest that NLG1 is an element that contributes to the coupling of neuronal activity to sleep/wake regulation.

KEYWORDS:

ChIP; EEG; gene expression; sleep homeostasis; synaptic plasticity

PMID:
23716671
PMCID:
PMC3683757
DOI:
10.1073/pnas.1221381110
[Indexed for MEDLINE]
Free PMC Article

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