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Elife. 2016 Aug 23;5. pii: e13424. doi: 10.7554/eLife.13424.

Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1.

Author information

  • 1Department of Biology, University of Pennsylvania, Philadelphia, United States.
  • 2Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen, The Netherlands.
  • 3Institute of Cardiovascular and Medical Science, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
  • 4LSA Molecular, Cellular, and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States.
  • 5Laboratory of Molecular Basis of Behavior, Head Nencki Institute of Experimental Biology, Warsaw, Poland.
  • 6Institute of Pharmaceutical Science, King's College London, London, United Kingdom.

Abstract

Brief periods of sleep loss have long-lasting consequences such as impaired memory consolidation. Structural changes in synaptic connectivity have been proposed as a substrate of memory storage. Here, we examine the impact of brief periods of sleep deprivation on dendritic structure. In mice, we find that five hours of sleep deprivation decreases dendritic spine numbers selectively in hippocampal area CA1 and increased activity of the filamentous actin severing protein cofilin. Recovery sleep normalizes these structural alterations. Suppression of cofilin function prevents spine loss, deficits in hippocampal synaptic plasticity, and impairments in long-term memory caused by sleep deprivation. The elevated cofilin activity is caused by cAMP-degrading phosphodiesterase-4A5 (PDE4A5), which hampers cAMP-PKA-LIMK signaling. Attenuating PDE4A5 function prevents changes in cAMP-PKA-LIMK-cofilin signaling and cognitive deficits associated with sleep deprivation. Our work demonstrates the necessity of an intact cAMP-PDE4-PKA-LIMK-cofilin activation-signaling pathway for sleep deprivation-induced memory disruption and reduction in hippocampal spine density.

KEYWORDS:

Sleep loss; hippocampus; mouse; neuroscience; synaptic plasticity

PMID:
27549340
PMCID:
PMC4996653
DOI:
10.7554/eLife.13424
[PubMed - in process]
Free PMC Article
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