title: Insufficient sleep reversibly alters bidirectional synaptic plasticity and NMDA receptor function.
abstract: Insufficient sleep impairs cognitive functions in humans and animals. However, whether long-term synaptic plasticity, a cellular substrate of learning and memory, is compromised by sleep loss per se remains unclear because of confounding factors related to sleep deprivation (SD) procedures in rodents. Using an ex vivo approach in C57BL/6J mice, we show that sleep loss rapidly and reversibly alters bidirectional synaptic plasticity in the CA1 area of the hippocampus. A brief (approximately 4 h) total SD, respecting the temporal parameters of sleep regulation and maintaining unaltered low corticosterone levels, shifted the modification threshold for long-term depression/long-term potentiation (LTP) along the stimulation frequency axis (1-100 Hz) toward the right. Reducing exposure to sensory stimuli by whisker trimming did not affect the SD-induced changes in synaptic plasticity. Recovery sleep reversed the effects induced by SD. When SD was combined with moderate stress, LTP induction was not only impaired but also occluded. Both electrophysiological analysis and immunoblotting of purified synaptosomes revealed that an alteration in the molecular composition of synaptically activated NMDA receptors toward a greater NR2A/NR2B ratio accompanied the effects of SD. This change was reversed after recovery sleep. By using an unparalleled, particularly mild form of SD, this study describes a novel approach toward dissociating the consequences of insufficient sleep on synaptic plasticity from nonspecific effects accompanying SD in rodents. We establish a framework for cellular models of cognitive impairment related to sleep loss, a major problem in modern society.
authors.affiliation: Department of Pharmacology and Neurobiology, Biozentrum, CH-4056 Basel, Switzerland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Kopp
authors.forename: Fabio
authors.initials: F
authors.lastname: Longordo
authors.forename: Janet R
authors.initials: JR
authors.lastname: Nicholson
authors.forename: Anita
authors.initials: A
authors.lastname: Lüthi
mesh_terms: D000818:Animals; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012890:Sleep / Q000502:physiology; D012892:Sleep Deprivation / Q000378:metabolism* / Q000503:physiopathology*; D013569:Synapses / Q000502:physiology*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate