Sleep Deprivation Causes Behavioral, Synaptic, and Membrane Excitability Alterations in Hippocampal Neurons

Abstract

Although the function of sleep remains elusive, several lines of evidence suggest that sleep has an important role in learning and memory. In light of the available data and with the prevalence of sleep deprivation (SD), we sought to determine the effect of SD on neuronal functioning. We found that the exposure of rats to 72 hr of primarily rapid eye movement SD impaired their subsequent performance on a hippocampus-dependent spatial learning task but had no effect on an amygdala-dependent learning task. To determine the underlying cellular level mechanisms of this hippocampal deficit, we examined the impact of SD on several fundamental aspects of membrane excitability and synaptic physiology in hippocampal CA1 pyramidal neurons and dentate gyrus granule cells. We found that neuronal excitability was severely reduced in CA1 neurons but not in granule cells and that the production of long-term potentiation of synaptic strength was inhibited in both areas. Using multiple SD methods we further attempted to differentiate the effects of sleep deprivation from those associated with the nonspecific stress induced by the sleep deprivation methods. Together these data suggest that failure to acquire adequate sleep produces several molecular and cellular level alterations that profoundly inhibit hippocampal functioning.

The impact of sleep loss on hippocampal function

“…Since this study, follow-up studies have given us an in-depth perspective on the effects of sleep deprivation on LTP. Researchers demonstrated that, similar to behavioral studies, LTP is vulnerable to total sleep deprivation, as well as to REM-specific sleep deprivation and fragmented sleep (McDermott et al 2003;Tartar et al 2006;Ravassard et al 2009;Florian et al 2011). Similar LTP deficits occurred after sleep deprivation in vivo in dentate gyrus-CA3 region (Romcy-Pereira and Pavlides 2004; Marks and Wayner 2005;Ishikawa et al 2006;Alhaider et al 2011).…”

“…Mice that are sleep-deprived post-training exhibit memory impairments in the hippocampus-dependent configuration of this task, but not in the hippocampus-independent configuration of the task (Graves et al 2003). Other studies examined sleep deprivation prior to learning in fear-conditioning tasks and observed similar results (Bueno et al 1994;McDermott et al 2003;Ruskin et al 2004;Ruskin and LaHoste 2009). The Y-maze or T-maze is another type of dissociation task where researchers can examine the learning strategies animals employ to perform the task (Oliveira et al 1997).…”

“…In contrast to the attenuation of LTP by sleep deprivation, researchers have observed either no change or facilitation of LTD after sleep deprivation in the hippocampus (McDermott et al 2003;Tadavarty et al 2009;Yang et al 2012). This discrepancy in the effect of sleep deprivation on LTD facilitation is likely due to experimental design differences in LTD-induction protocol as well as to different sleep-deprivation manipulations.…”

“…Extended periods of sleep deprivation for 24-72 h appear to eliminate or reduce LTP induction in vitro (Campbell et al 2002;McDermott et al 2003). However, brief periods of sleep deprivation only appear to disrupt signaling underlying LTP maintenance while induction remains intact (Vecsey et al 2009;Florian et al 2011).…”

“…This discrepancy in the effect of sleep deprivation on LTD facilitation is likely due to experimental design differences in LTD-induction protocol as well as to different sleep-deprivation manipulations. For instance, while Tadavarty et al (2009) used gentle handling to sleep deprive animals, allowing them to examine the circadian contribution, McDermott et al (2003) used the multiple platform method to have a 72-h period of REM sleep deprivation. Similarly, Yang et al (2012) examined circadian contribution along with sleep pressure on the resulting LTD. Additionally, in vitro preparations were used in earlier cases of observed LTD facilitation after sleep deprivation (Tadavarty et al 2009(Tadavarty et al , 2011.…”