Several theories concerning sleep function posit that sleep serves to maintain, repair or consolidate synapses. Several lines of evidence support these theories but, to date, there has been no direct test of these hypotheses. An independent large literature relates long-term memory tasks to synaptic plasticity. Further, a few studies have demonstrated a clear influence of sleep on memory consolidation and of learning tasks on sleep. However, there are heretofore, no studies of the influence of sleep on synaptic plasticity despite the theoretical foundation for such studies and the fact that the necessary molecular tools and mouse models are now available. To test the general hypothesis that sleep has a role in synaptic plasticity we will use a non-cognitive stimulus (a unilateral whisker cut) and a cognitive stimulus (a spatial learning test) to induce synaptic plasticity in the somatosensory cotex and the hippocampus respectively. The effects of sleep loss and excess sleep in these experimental paradigms on the magnitude and rates of change of a variety of molecular markers of synaptic plasticity will be determined. The markers to be analyzed represent six classes of molecules necessary for synaptic remodeling; extracellular matrix proteins, cell adhesion molecules, growth factors, neurotransmission related proteins, cytoskeletal and associated proteins and transcription factors. Three strains of mice will be used, AKR/J, acallosal mice and a transgenic strain carrying the lac-Z gene coupled to a promoter dependent upon the presence of nuclear factor Kappa B. In addition to quantifying the changes in the molecular markers of synaptic plasticity in extracts of small areas of the brain, we will also determine the specific location of cell types in which these molecules change in response to sleep manipulation using histochemistry, immunocytochemistry and in situ hybridization histochemistry. Expected results will provide the foundations for the experimental verification of sleep function.
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