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

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

doi:10.7554/eLife.13424

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

Journal article

Open access

Peer reviewed

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

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, …

eLife, Vol.5, e13424

08/23/2016

DOI: 10.7554/eLife.13424

PMCID: PMC4996653

PMID: 27549340

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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.

Actin Depolymerizing Factors - metabolism

Memory Disorders

Animals

CA1 Region, Hippocampal - physiology

Dendritic Spines - physiology

Neurons - physiology

Neurons - cytology

Mice

Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism

Sleep Deprivation - complications

Details

Title: Subtitle: Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1
Creators: Robbert Havekes - Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen, The Netherlands
Alan J Park - Department of Biology, University of Pennsylvania, Philadelphia, United States
Jennifer C Tudor - Department of Biology, University of Pennsylvania, Philadelphia, United States
Vincent G Luczak - Department of Biology, University of Pennsylvania, Philadelphia, United States
Rolf T Hansen - Department of Biology, University of Pennsylvania, Philadelphia, United States
Sarah L Ferri - Department of Biology, University of Pennsylvania, Philadelphia, United States
Vibeke M Bruinenberg - Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen, The Netherlands
Shane G Poplawski - Department of Biology, University of Pennsylvania, Philadelphia, United States
Jonathan P Day - Institute of Cardiovascular and Medical Science, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
Sara J Aton - LSA Molecular, Cellular, and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States
Kasia Radwańska - Laboratory of Molecular Basis of Behavior, Head Nencki Institute of Experimental Biology, Warsaw, Poland
Peter Meerlo - Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen, The Netherlands
Miles D Houslay - Institute of Pharmaceutical Science, King's College London, London, United Kingdom
George S Baillie - Institute of Cardiovascular and Medical Science, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
Ted Abel - Department of Biology, University of Pennsylvania, Philadelphia, United States
Resource Type: Journal article
Publication Details: eLife, Vol.5, e13424
DOI: 10.7554/eLife.13424
PMID: 27549340
PMCID: PMC4996653
NLM abbreviation: Elife
eISSN: 2050-084X
Publisher: England
Grant note: MR/J007412/1 / Medical Research Council P01 AG017628 / NIA NIH HHS DP2 MH104119 / NIMH NIH HHS 5K12GM081529 / NIGMS NIH HHS R01 MH086415 / NIMH NIH HHS T32 NS007413 / NINDS NIH HHS
Language: English
Date published: 08/23/2016
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Stead Family Department of Pediatrics; Psychological and Brain Sciences; Iowa Neuroscience Institute; Developmental and Behavioral Pediatrics; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
Record Identifier: 9984070894102771

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