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Homer1a drives homeostatic scaling-down of excitatory synapses during sleep

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Science  03 Feb 2017:
Vol. 355, Issue 6324, pp. 511-515
DOI: 10.1126/science.aai8355

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Synapse remodeling during sleep

General activity and information processing while an animal is awake drive synapse strengthening. This is counterbalanced by weakening of synapses during sleep (see the Perspective by Acsády). De Vivo et al. used serial scanning electron microscopy to reconstruct axon-spine interface and spine head volume in the mouse brain. They observed a substantial decrease in interface size after sleep. The largest relative changes occurred among weak synapses, whereas strong ones remained stable. Diering et al. found that synapses undergo changes in synaptic glutamate receptors during the sleep-wake cycle, driven by the immediate early gene Homer1a. In awake animals, Homer1a accumulates in neurons but is excluded from synapses by high levels of noradrenaline. At the onset of sleep, noradrenaline levels decline, allowing Homer1a to move to excitatory synapses and drive synapse weakening.

Science, this issue p. 457, p. 507; see also p. 511

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.

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