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Nat Commun. 2016 Jan 27;7:10512. doi: 10.1038/ncomms10512.

ADAR-mediated RNA editing suppresses sleep by acting as a brake on glutamatergic synaptic plasticity.

Author information

1
Department of Pharmacology, University of California San Diego, La Jolla, California 92093-0636, USA.
2
Biomedical Sciences Graduate Program and Molecular Pharmacology Training Grant, University of California San Diego, La Jolla, California 92093-0636, USA.
3
Department of Neurobiology, University of Southern California, Los Angeles, California 90089-2520, USA.
4
Neurosciences Graduate Program, University of California San Diego, La Jolla, California 92093-0636, USA.
5
Center for Circadian Biology, University of California San Diego, La Jolla, California 92093-0636, USA.

Abstract

It has been postulated that synaptic potentiation during waking is offset by a homoeostatic reduction in net synaptic strength during sleep. However, molecular mechanisms to support such a process are lacking. Here we demonstrate that deficiencies in the RNA-editing gene Adar increase sleep due to synaptic dysfunction in glutamatergic neurons in Drosophila. Specifically, the vesicular glutamate transporter is upregulated, leading to over-activation of NMDA receptors, and the reserve pool of glutamatergic synaptic vesicles is selectively expanded in Adar mutants. Collectively these changes lead to sustained neurotransmitter release under conditions that would otherwise result in synaptic depression. We propose that a shift in the balance from synaptic depression towards synaptic potentiation in sleep-promoting neurons underlies the increased sleep pressure of Adar-deficient animals. Our findings provide a plausible molecular mechanism linking sleep and synaptic plasticity.

PMID:
26813350
PMCID:
PMC4737855
DOI:
10.1038/ncomms10512
[Indexed for MEDLINE]
Free PMC Article

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