Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1
- University of Pennsylvania, United States
- Columbia University, United States
- University of Groningen, Netherlands
- University of Glasgow, United Kingdom
- University of Michigan, United States
- Nencki Institute of Experimental Biology, Poland
- King's College 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.
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Funding
National Institutes of Health (1RO1MH086415)
- Ted Abel
National Institutes of Health (RO1, AG017628)
- Ted Abel
Netherlands organization for Scientific Research (postdoctoral fellowship 825.07.029)
- Robbert Havekes
University of Pennsylvania (UPENN rsearch foundation grant)
- Robbert Havekes
- Ted Abel
National Institutes of Health (postdoctoral fellowship, 5K12GM081529)
- Jennifer C Tudor
National Institutes of Health (postdoctoral fellowship, T32 NS077413)
- Sarah L Ferri
European Commission (FP7-PEOPLE-2009-RG-Alco_CaMK)
- Kasia Radwańska
NCN grant Harmonia 2013/08/m/NZ3/00861 (Research grant)
- Kasia Radwańska
Medical Research Council (Grant MR/J007412/1)
- George S Baillie
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC protocols 804240, 804407, 802784) of the University of Pennsylvania and Head Necki Institute of Experimental Biology, Warsaw.
Copyright
© 2016, Havekes et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1
eLife 5:e13424.
https://doi.org/10.7554/eLife.13424
