Sleep deprivation impairs spatial working memory and reduces hippocampal AMPA receptor phosphorylation

Hagewoud, R., Havekes, R., Novati, A., Keijser, J. N., van der Zee, E. A. & Meerlo, P., Jun-2010, In : Journal of Sleep Research. 19, 2, p. 280-288 9 p.

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  • Sleep deprivation impairs spatial working memory

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Sleep is important for brain function and cognitive performance. Sleep deprivation (SD) may affect subsequent learning capacity and ability to form new memories, particularly in the case of hippocampus-dependent tasks. In the present study we examined whether SD for 6 or 12 h during the normal resting phase prior to learning affects hippocampus-dependent working memory in mice. In addition, we determined effects of SD on hippocampal glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and their regulatory pathways, which are crucially involved in working memory. After 12 h SD, but not yet after 6 h, spatial working memory in a novel arm recognition task was significantly impaired. This deficit was not likely due to stress as corticosterone levels after SD were not significantly different between groups. In parallel with the change in cognitive function, we found that 12 h SD significantly reduced hippocampal AMPA receptor phosphorylation at the GluR1-S845 site, which is important for incorporation of the receptors into the membrane. SD did not affect protein levels of cyclic-AMP-dependent protein kinase A (PKA) or phosphatase calcineurin (CaN), which regulate GluR1 phosphorylation. However, SD did reduce the expression of the scaffolding molecule A-kinase anchoring protein 150 (AKAP150), which binds and partly controls the actions of PKA and CaN. In conclusion, a relatively short SD during the normal resting phase may affect spatial working memory in mice by reducing hippocampal AMPA receptor function through a change in AKAP150 levels. Together, these findings provide further insight into the possible mechanism of SD-induced hippocampal dysfunction and memory impairment.

Original languageEnglish
Pages (from-to)280-288
Number of pages9
JournalJournal of Sleep Research
Issue number2
Publication statusPublished - Jun-2010


  • sleep, sleep homeostasis, sleep function, sleep loss, sleep deprivation, sleep restriction, learning, spatial learning, maze learning, memory, memory formation, working memory, cognition, brain, behavior, glutamate receptors, NMDA, AMPA, protein kinase A, PKA, A Kinase Anchor Proteins, AKAP, neuronal plasticity, synaptic plasticity

ID: 5088646