Research ReportParadoxical sleep deprivation impairs spatial learning and affects membrane excitability and mitochondrial protein in the hippocampus
Introduction
There is growing evidence that sleep and learning are interconnected. Both human and animal studies have shown that sleep has a key role in learning and memory. Rapid eye movement (REM) sleep is increased following learning sessions (Smith and Rose, 1997, Mandai et al., 1989), and sleep deprivation interferes with learning and memory (Silvestri, 2005, Guan et al., 2004). A number of animal studies have gone on to explore the potential cellular and molecular underpinnings of sleep deprivation-induced learning deficits, and many of these studies have focused on changes in transmitters (Banks et al., 2002, Hipolide et al., 2005), the impairment of formation of long-term potentiation (Campbell et al., 2002, Davis et al., 2003), and effects on extracellular signal-regulated kinases (Kelleher et al., 2004, Guan et al., 2004). Less attention has been given to the effects of sleep deprivation on the intrinsic properties of neurons. Limited animal studies indicated that the firing patterns of neurons in the hippocampus and cortex involved in the learning experience were replayed during subsequent sleep (Louie and Wilson, 2001, Skaggs and McNaughton, 1996, Sutherl and McNaughton, 2000), and REM sleep deprivation reduced the basic excitability of hippocampal neurons (McDermott et al., 2003). However, the molecular mechanism of changes of neuron properties induced by sleep deprivation remains poorly understood.
Given the well recognized cognitive effects and the prevalence of sleep deprivation in society today, investigating the effects of sleep deprivation on cellular physiology and related mechanisms is of interest. The present study investigated the effect of paradoxical sleep deprivation (PSD) on spatial learning and memory with the Morris Water Maze, which is commonly used to examine hippocampal function (Walker and Stickgold, 2006, Smith and Rose, 1996). In addition we examined possible mechanisms by investigating the effects of PSD on membrane excitability and mitochondria of hippocampal CA1 pyramidal neurons.
Using the Morris Water Maze spatial learning set protocol, we have found that PSD rats are slower to learn the location of the platform than control groups, but are capable of successfully performing the task with repeated exposure to the test. During the probe trial, the PSD rats tended to spend slightly less time in the target quadrant compared with the control groups, but this effect did not quite reach significance. The data from the behavior tests indicated that PSD impairs the ability of spatial learning of rats. There were indications of minor effects on working memory and maintenance of established memory as well, but most of these did not quite reach significance. We further have found that PSD induces translocation of Bax to mitochondria and cytochrome c release into cytoplasm, and decreases the membrane excitability of CA1 pyramidal neurons, which may contribute the deficits in performing the spatial learning task.
Section snippets
PSD impairs spatial learning
To test for the impact of PSD on memory formation, a group of rats was REM sleep-deprived for 5 days, and a second group of rats (LP) was placed on large platforms as a control group to simulate the PSD condition while allowing sleep to occur, and the third group of rats was maintained in their home cages as another control group. Daily, the rats were tested between 150:0 h and 18:00 h, in a place-learning set paradigm using the water maze as described in Experimental procedures. Initial body
Discussion
Sleep is composed of two prominent types: rapid eye movement (REM) sleep and non-REM (NREM) sleep, and both of them differently modulate the consolidation of declarative and nondeclarative memories, respectively (Peigneux et al., 2004). Rapid eye movement (REM) sleep is increased following learning sessions (Smith and Rose, 1997, Mandai et al., 1989), previously learned information and new associations can be formed during REM, and information processed during REM can be transferred to the
Subjects
A total of 77 adult (180–200 g) male Sprague–Dawley rats were used in the experiments. Animal care was in accord with the “Principles of Medical Laboratory Animal Care” issued by the National Ministry of Health. All experiments conformed to the guidelines of the “National Ordinances on Experimental Animals” for the ethical use of animals. All animals were kept at 24 °C (room temperature) with light from 07:00 to 19:00 h.
Paradoxical sleep deprivation
Ten small platforms (8.5 cm in height and 6.0 cm in diameter) were placed
Acknowledgments
We thank Dr Judith Strong for her helpful comments on this manuscript. This work was supported by an NSFC grant (30530260) from China and a grant from the Fourth Military Medical University (XJ200502).
References (36)
- et al.
REM sleep deprivation-induced deficits in the latency-to-peak induction and maintenance of long-term potentiation within the CA1 region of the hippocampus
Brain Res.
(2003) The hippocampus and mechanisms of declarative memory
Behav. Brain Res.
(1999)- et al.
Sleep and memory: a molecular perspective
Trends Neurosci.
(2001) - et al.
Sleep deprivation impairs spatial memory and decreases extracellular signal-regulated kinase phosphorylation in the hippocampus
Brain Res.
(2004) - et al.
Processing of learned information in paradoxical sleep: relevance for memory
Behav. Brain Res.
(1995) - et al.
Distinct effects of sleep deprivation on binding to norepinephrine and serotonin transporters in rat brain
Progress in Neuro-Psychopharmacology & Biological Psychiatry
(2005) - et al.
Translational regulatory mechanisms in persistent forms of synaptic plasticity
Neuron
(2004) - et al.
Suppression of apoptosis by calorie restriction in aged kidney
Exp. Gerontol.
(2004) - et al.
Temporally structured replay of awake hippocampal ensemble activity during rapid eye movement sleep
Neuron
(2001) - et al.
REM sleep modifications following a Morse code learning session in humans
Physiol. Behav.
(1989)