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

Havekes, R., Park, A. J., Tudor, J. C., Luczak, V. G., Hansen, R. T., Ferri, S. L., Bruinenberg, V. M., Poplawski, S. G., Day, J. P., Aton, S. J., Radwańska, K., Meerlo, P., Houslay, M. D., Baillie, G. S. & Abel, T., 23-Aug-2016, In : eLife. 5, 22 p., 13424.

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DOI

  • Robbert Havekes
  • Alan J Park
  • Jennifer C Tudor
  • Vincent G Luczak
  • Rolf T Hansen
  • Sarah L Ferri
  • Vibeke M Bruinenberg
  • Shane G Poplawski
  • Jonathan P Day
  • Sara J Aton
  • Kasia Radwańska
  • Peter Meerlo
  • Miles D Houslay
  • George S Baillie
  • Ted Abel

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.

Original languageEnglish
Article number13424
Number of pages22
JournaleLife
Volume5
Publication statusPublished - 23-Aug-2016

    Keywords

  • LONG-TERM POTENTIATION, ACTIN DEPOLYMERIZING FACTOR, PROTEIN-KINASE-A, SYNAPTIC PLASTICITY, DENDRITIC SPINES, COFILIN-PHOSPHORYLATION, STRUCTURAL PLASTICITY, SUBSEQUENT SLEEP, SPATIAL MEMORY, DYNAMICS
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