NR2A at CA1 synapses is obligatory for the susceptibility of hippocampal plasticity to sleep loss

J Neurosci. 2009 Jul 15;29(28):9026-41. doi: 10.1523/JNEUROSCI.1215-09.2009.


A loss in the necessary amount of sleep alters expression of genes and proteins implicated in brain plasticity, but key proteins that render neuronal circuits sensitive to sleep disturbance are unknown. We show that mild (4-6 h) sleep deprivation (SD) selectively augmented the number of NR2A subunits of NMDA receptors on postsynaptic densities of adult mouse CA1 synapses. The greater synaptic NR2A content facilitated induction of CA3-CA1 long-term depression in the theta frequency stimulation range and augmented the synaptic modification threshold. NR2A-knock-out mice maintained behavioral response to SD, including compensatory increase in post-deprivation resting time, but hippocampal synaptic plasticity was insensitive to sleep loss. After SD, the balance between synaptically activated and slowly recruited NMDA receptor pools during temporal summation was disrupted. Together, these results indicate that NR2A is obligatory for the consequences of sleep loss on hippocampal synaptic plasticity. These findings could advance pharmacological strategies aiming to sustain hippocampal function during sleep restriction.

Publication types

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

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / genetics
  • Analysis of Variance
  • Animals
  • Biophysics
  • Chi-Square Distribution
  • Drug Combinations
  • Electric Stimulation / methods
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / genetics
  • GABA Antagonists / pharmacology
  • Hippocampus / pathology*
  • Hippocampus / ultrastructure
  • In Vitro Techniques
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Immunoelectron / methods
  • Neuronal Plasticity / genetics*
  • Neurons / metabolism
  • Neurons / pathology
  • Neurons / physiology
  • Picrotoxin / pharmacology
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / deficiency
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Sleep Deprivation / pathology*
  • Sleep Deprivation / physiopathology*
  • Synapses / metabolism*
  • Synapses / ultrastructure
  • Time Factors


  • Drug Combinations
  • Excitatory Amino Acid Antagonists
  • GABA Antagonists
  • NR2A NMDA receptor
  • NR2B NMDA receptor
  • Receptors, N-Methyl-D-Aspartate
  • Picrotoxin