title: Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1.
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.
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, United States.|Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen, The Netherlands.
authors.forename: Robbert
authors.initials: R
authors.lastname: Havekes
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, United States.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Park
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, United States.
authors.forename: Jennifer C
authors.identifier: 0000-0002-3826-3012
authors.initials: JC
authors.lastname: Tudor
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, United States.
authors.forename: Vincent G
authors.initials: VG
authors.lastname: Luczak
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, United States.
authors.forename: Rolf T
authors.initials: RT
authors.lastname: Hansen
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, United States.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Ferri
authors.affiliation: Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen, The Netherlands.
authors.forename: Vibeke M
authors.initials: VM
authors.lastname: Bruinenberg
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, United States.
authors.forename: Shane G
authors.initials: SG
authors.lastname: Poplawski
authors.affiliation: Institute of Cardiovascular and Medical Science, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Day
authors.affiliation: LSA Molecular, Cellular, and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States.
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Aton
authors.affiliation: Laboratory of Molecular Basis of Behavior, Head Nencki Institute of Experimental Biology, Warsaw, Poland.
authors.forename: Kasia
authors.initials: K
authors.lastname: Radwańska
authors.affiliation: Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Meerlo
authors.affiliation: Institute of Pharmaceutical Science, King's College London, London, United Kingdom.
authors.forename: Miles D
authors.initials: MD
authors.lastname: Houslay
authors.affiliation: Institute of Cardiovascular and Medical Science, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: George S
authors.initials: GS
authors.lastname: Baillie
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, United States.
authors.forename: Ted
authors.identifier: 0000-0003-2423-4592
authors.initials: T
authors.lastname: Abel
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism; D049229:Dendritic Spines / Q000502:physiology; D008569:Memory Disorders; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D012892:Sleep Deprivation / Q000150:complications*
chemical_list: D051339:Actin Depolymerizing Factors; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C095813:Pde4a protein, mouse
keywords: Sleep loss; hippocampus; mouse; neuroscience; synaptic plasticity