Homer1a drives homeostatic scaling-down of excitatory synapses during sleep

Graham H. Diering, Raja S. Nirujogi, Richard H. Roth, Paul F. Worley, Akhilesh Pandey, Richard L. Huganir

Research output: Contribution to journalArticle

151 Scopus citations

Abstract

Sleep is an essential process that supports learning and memory by acting on synapses through poorly understood molecular mechanisms. Using biochemistry, proteomics, and imaging in mice, we find that during sleep, synapses undergo widespread alterations in composition and signaling, including weakening of synapses through removal and dephosphorylation of synaptic AMPA-type glutamate receptors. These changes are driven by the immediate early gene Homer1a and signaling from group I metabotropic glutamate receptors mGluR1/5. Homer1a serves as a molecular integrator of arousal and sleep need via the wake- and sleep-promoting neuromodulators, noradrenaline and adenosine, respectively. Our data suggest that homeostatic scaling-down, a global form of synaptic plasticity, is active during sleep to remodel synapses and participates in the consolidation of contextual memory.

Original languageEnglish (US)
Pages (from-to)511-515
Number of pages5
JournalScience
Volume355
Issue number6324
DOIs
StatePublished - Feb 3 2017
Externally publishedYes

ASJC Scopus subject areas

  • General

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    Diering, G. H., Nirujogi, R. S., Roth, R. H., Worley, P. F., Pandey, A., & Huganir, R. L. (2017). Homer1a drives homeostatic scaling-down of excitatory synapses during sleep. Science, 355(6324), 511-515. https://doi.org/10.1126/science.aai8355