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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Deaminase / genetics
  • Adenosine Deaminase / metabolism*
  • Animals
  • Drosophila / enzymology*
  • Drosophila / genetics
  • Drosophila / physiology*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Female
  • Glutamic Acid / metabolism*
  • Male
  • Neuronal Plasticity*
  • Neurons / metabolism
  • Neurotransmitter Agents / metabolism
  • RNA Editing
  • Sleep
  • Synaptic Vesicles / metabolism


  • Drosophila Proteins
  • Neurotransmitter Agents
  • Glutamic Acid
  • Adar protein, Drosophila
  • Adenosine Deaminase