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.
journal_name
Elifejournal_title
eLifeauthors
Havekes R,Park AJ,Tudor JC,Luczak VG,Hansen RT,Ferri SL,Bruinenberg VM,Poplawski SG,Day JP,Aton SJ,Radwańska K,Meerlo P,Houslay MD,Baillie GS,Abel Tdoi
10.7554/eLife.13424subject
Has Abstractpub_date
2016-08-23 00:00:00issn
2050-084Xjournal_volume
5pub_type
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