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

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 fin...

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Bibliographic Details
Published in:eLife 2016-08, Vol.5
Main Authors: Havekes, Robbert, Park, Alan J, Tudor, Jennifer C, Luczak, Vincent G, Hansen, Rolf T, Ferri, Sarah L, Bruinenberg, Vibeke M, Poplawski, Shane G, Day, Jonathan P, Aton, Sara J, Radwańska, Kasia, Meerlo, Peter, Houslay, Miles D, Baillie, George S, Abel, Ted
Format: Article
Language:English
Subjects:
Actin
Actin Depolymerizing Factors - metabolism
Animals
Biology
CA1 Region, Hippocampal - physiology
Cofilin
Cognitive ability
Complications and side effects
Cyclic AMP
Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism
Dendritic spines
Dendritic Spines - physiology
Health aspects
Hippocampal plasticity
Hippocampus
Hippocampus (Brain)
Life sciences
Long term memory
Memory
Memory Disorders
Memory, Disorders of
Mice
Neural networks
Neurons - cytology
Neurons - physiology
Neuroscience
Phosphodiesterase
Phosphorylation
Protein kinase A
Risk factors
Signal transduction
Sleep deprivation
Sleep Deprivation - complications
Sleep loss
Synaptic plasticity
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Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/elife.13424