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

Abstract

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 GSK3β 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.

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Figure 1: Molecular correlates of LTP/LTD in wakefulness and sleep.
Figure 2: Electrophysiological correlates of LTP and LTD in wakefulness and sleep.
Figure 3: Effect of behavioral state on the LFP responses.
Figure 4: Molecular correlates of LTP/LTD after enforced wakefulness.
Figure 5: Electrophysiological correlates of LTP/LTD after enforced wakefulness.
Figure 6: Relationship between LFP response slope and sleep slow-wave homeostasis.
Figure 7: Partial LTP occlusion after wakefulness.

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Acknowledgements

We thank M.F. Bear and his laboratory for help in optimizing the synaptoneurosome preparations. This work was supported by a US NIH Director's Pioneer award to G.T. and Swiss National Science Foundation grant PBZHB-106264 to V.V.V.

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C.C. and M.P.-G. carried out the molecular experiments. V.V.V. performed the electrophysiological experiments and wrote part of the manuscript. U.F. participated in some of the electrophysiological experiments. C.C. and G.T. designed the experiments, coordinated the development of the study and wrote most of the manuscript.

Corresponding authors

Correspondence to Chiara Cirelli or Giulio Tononi.

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Vyazovskiy, V., Cirelli, C., Pfister-Genskow, M. et al. Molecular and electrophysiological evidence for net synaptic potentiation in wake and depression in sleep. Nat Neurosci 11, 200–208 (2008). https://doi.org/10.1038/nn2035

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