We spend a third of our life asleep, and even partial sleep deprivation has serious consequences on cognition, mood, and health, suggesting that sleep must serve some fundamental functions. Presently, we lack a neurobiological understanding of what these functions might be. We know that sleep is tightly regulated as a function of prior wakefulness and sleep pressure is reflected by the amount of slow wave activity (SWA) in the EEG of non-rapid eye movement (NREM) sleep. SWA (the EEG power density between 0.5 and 4.5 Hz) increases in proportion to the time spent awake and decreases during sleep, but why this is the case remains unclear. The overall goal of this proposal is to test a recent hypothesis concerning the function of NREM sleep - the synaptic homeostasis hypothesis (SHY). The hypothesis states that plastic processes during wakefulness result in a net increase in synaptic strength in many brain circuits;such increased synaptic weight comes at the expense of increased metabolic consumption. Strengthened brain circuits lead to larger SWA during subsequent sleep. In turn, sleep SWA renormalizes synaptic strength to a baseline level that is energetically sustainable and beneficial for memory and performance. This proposal will test two predictions of SHY: sleep slow waves are necessary for the renormalization of cortical circuits after learning (Aim 1);and sleep slow waves are necessary for the enhancement of performance after sleep (Aim 2). To do so, I will use high density EEG recordings in humans while performing a visuomotor learning task (rotation learning) that involves right parietal cortex and during post learning sleep. Sleep slow waves will be suppressed using mild acoustic stimuli that do not fragment sleep. Control experiments will apply the same number of stimuli during stage 2 sleep.
The specific aims are designed to evaluate if, as predicted by SHY, learning leaves a local trace in the waking EEG that is renormalized after sleep, and if the selective deprivation of sleep slow waves leads to a persistence of such EEG traces and to a suppression of post-sleep performance enhancement.

Public Health Relevance

There is overwhelming evidence that restorative sleep is necessary to human health, that sleep deprivation and restriction have enormous social costs, and that sleep disorders are extremely common and are frequently associated with psychiatric and neurological disorders. By tying brain plasticity and performance to SWA, the results of this investigation will advance our understanding of the function of sleep at a fundamental level, lend support to SHY, and provide a rational basis for designing therapeutic approaches that focus on the quality of SWA and enhance the restorative effects of sleep in health and disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30MH082601-02
Application #
7735588
Study Section
Special Emphasis Panel (ZRG1-F01-V (20))
Program Officer
Vogel, Michael W
Project Start
2008-12-01
Project End
2012-11-30
Budget Start
2009-12-01
Budget End
2010-11-30
Support Year
2
Fiscal Year
2010
Total Cost
$31,784
Indirect Cost
Name
University of Wisconsin Madison
Department
Psychiatry
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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Plante, D T; Goldstein, M R; Landsness, E C et al. (2013) Altered overnight modulation of spontaneous waking EEG reflects altered sleep homeostasis in major depressive disorder: a high-density EEG investigation. J Affect Disord 150:1167-73
Goldstein, M R; Plante, D T; Hulse, B K et al. (2012) Overnight changes in waking auditory evoked potential amplitude reflect altered sleep homeostasis in major depression. Acta Psychiatr Scand 125:468-77
Plante, David T; Landsness, Eric C; Peterson, Michael J et al. (2012) Sex-related differences in sleep slow wave activity in major depressive disorder: a high-density EEG investigation. BMC Psychiatry 12:146
Plante, David T; Landsness, Eric C; Peterson, Michael J et al. (2012) Altered slow wave activity in major depressive disorder with hypersomnia: a high density EEG pilot study. Psychiatry Res 201:240-4
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