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 (ϳ4 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.

A review of lifestyle factors that contribute to important pathways associated with major depression: Diet, sleep and exercise

“…Experimental studies show that prolonged sleep restriction or disruption affects hippocampal integrity (Guzman-Marin et al, 2006, Kopp et al, 2006, McDermott et al, 2003, Roman et al, 2005a. For example, in young male rats, one month of chronic sleep restriction reduced dorsal hippocampal volume by 10% (Novati et al, 2011).…”

The impact of sleep loss on hippocampal function

“…No studies have specifically examined the time course of sleep deprivation to impair LTP. However, Kopp et al (2006) have demonstrated that as little as 4 h of sleep deprivation can impair LTP in vitro. In terms of in vivo experiments that have examined the time course of sleep deprivation, Marks and Wayner (2005) found that 3, 6, and 9 h of sleep deprivation impaired LTP, demonstrating that even an acute 3-h period of sleep deprivation is sufficient to impair synaptic plasticity.…”

“…Although both of these studies observed clear differences in trafficking and NMDA receptor-mediated current using extended periods of sleep deprivation, these findings conflict with findings from briefer periods of sleep deprivation (Vecsey et al 2009). Using electron microscopy, Kopp and colleagues found that 4 h of sleep deprivation by exposure to a novel environment and introduction to new nesting material increased the NR2A/NR2B NMDA-receptor subunit ratio as well as total NR2A subunits in the hippocampus (Kopp et al 2006;Longordo et al 2009). This finding was correlated with a shift in the frequency needed to elicit LTD and LTP, decreasing the threshold frequency to induce LTD and increasing the threshold frequency to induce LTP.…”

Rapid eye movement sleep deprivation decreases long-term potentiation stability and affects some glutamatergic signaling proteins during hippocampal development

“…REMS-deprivation causes an increase in serum corticosterone levels in the adult rat (Kopp et al, 2006;McDermott et al, 2003). High levels of corticosterone are known to affect LTP induction in the hippocampus.…”