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- Title
The p75 Neurotrophin Receptor Is an Essential Mediator of Impairments in Hippocampal-Dependent Associative Plasticity and Memory Induced by Sleep Deprivation.
- Authors
Lik-Wei Wong; Tann, Jason Y.; Ibanez, Carlos F.; Sajikumar, Sreedharan
- Abstract
Sleep deprivation (SD) interferes with hippocampal structural and functional plasticity, formation of long-term memory and cognitive function. The molecular mechanisms underlying these effects are incompletely understood. Here, we show that SD impaired synaptic tagging and capture and behavioral tagging, two major mechanisms of associative learning and memory. Strikingly, mutant male mice lacking the p75 neurotrophin receptor (p75NTR) were resistant to the detrimental effects of SD on hippocampal plasticity at both cellular and behavioral levels. Mechanistically, SD increased p75NIR expression and its interaction with phosphodiesterase. p75NTR deletion preserved hippocampal structural and functional plasticity by preventing SD-mediated effects on hippocampal cAMP-CREB-BDNF, cAMP-PKA-LIMKl-cofdin, and RhoA-ROCK2 pathways. Our study identifies p75NTR as an important mediator of hippocampal structural and functional changes associated with SD, and suggests that targeting p75NTR could be a promising strategy to limit the memory and cognitive deficits that accompany sleep loss.
- Subjects
NEUROTROPHIN receptors; SLEEP deprivation; LONG-term memory; ASSOCIATIVE learning; LONG-term synaptic depression; MEMORY
- Publication
Journal of Neuroscience, 2019, Vol 39, Issue 28, p5452
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.2876-18.2019