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Mol Brain. 2011 Mar 9;4:11. doi: 10.1186/1756-6606-4-11.

Activity-dependent brain-derived neurotrophic factor expression regulates cortistatin-interneurons and sleep behavior.

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  • 1Genes, Cognition and Psychosis Program (GCAP), National Institute of Mental Health (NIMH), Bethesda, MD 20892, USA.



Sleep homeostasis is characterized by a positive correlation between sleep length and intensity with the duration of the prior waking period. A causal role for brain-derived neurotrophic factor (BDNF) in sleep homeostasis has been suggested, but the underlying mechanisms remain unclear. Cortistatin, a neuropeptide expressed primarily in a subset of cortical GABAergic interneurons, is another molecule implicated in sleep homeostasis.


We confirmed that sleep deprivation leads to an increase in cortical cortistatin mRNA expression. Disruption of activity-dependent BDNF expression in a genetically modified mouse line impairs both baseline levels of cortistatin mRNA as well as its levels following sleep deprivation. Disruption of activity-dependent BDNF also leads to a decrease in sleep time during the active (dark) phase.


Our studies suggest that regulation of cortistatin-expressing interneurons by activity-dependent BDNF expression may contribute to regulation of sleep behavior.

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