Molecular and electrophysiological evidence for net synaptic potentiation in wake and depression in sleep

Nat Neurosci. 2008 Feb;11(2):200-8. doi: 10.1038/nn2035. Epub 2008 Jan 20.


Plastic changes occurring during wakefulness aid in the acquisition and consolidation of memories. For some memories, further consolidation requires sleep, but whether plastic processes during wakefulness and sleep differ is unclear. We show that, in rat cortex and hippocampus, GluR1-containing AMPA receptor (AMPAR) levels are high during wakefulness and low during sleep, and changes in the phosphorylation states of AMPARs, CamKII and GSK3beta are consistent with synaptic potentiation during wakefulness and depression during sleep. Furthermore, slope and amplitude of cortical evoked responses increase after wakefulness, decrease after sleep and correlate with changes in slow-wave activity, a marker of sleep pressure. Changes in molecular and electrophysiological indicators of synaptic strength are largely independent of the time of day. Finally, cortical long-term potentiation can be easily induced after sleep, but not after wakefulness. Thus, wakefulness appears to be associated with net synaptic potentiation, whereas sleep may favor global synaptic depression, thereby preserving an overall balance of synaptic strength.

Publication types

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

MeSH terms

  • Animals
  • Behavior, Animal
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Cerebral Cortex / cytology
  • Electroencephalography / methods
  • Electromyography / methods
  • Gene Expression Regulation / physiology*
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Hippocampus / cytology
  • Male
  • Neuronal Plasticity / physiology*
  • Phosphorylation
  • Rats
  • Rats, Inbred WKY
  • Receptors, AMPA / metabolism
  • Serine / metabolism
  • Sleep / physiology*
  • Synapses / physiology*
  • Temperature
  • Threonine / metabolism
  • Wakefulness / physiology*


  • Receptors, AMPA
  • Threonine
  • Serine
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, rat
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Glycogen Synthase Kinase 3
  • glutamate receptor ionotropic, AMPA 1