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

First Author  El Helou J Year  2013
Journal  Proc Natl Acad Sci U S A Volume  110
Issue  24 Pages  9974-9
PubMed ID  23716671 Mgi Jnum  J:197398
Mgi Id  MGI:5492265 Doi  10.1073/pnas.1221381110
Citation  El Helou J, et al. (2013) Neuroligin-1 links neuronal activity to sleep-wake regulation. Proc Natl Acad Sci U S A 110(24):9974-9
abstractText  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.
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