Levels of activity of single cells in widespread areas of the brain have been found to be differentially influenced by stage of sleep. This phenomenon appears to be a basic sleep behavior process, and one that may be related to the functions of the stages of sleep. The specific brain mechanism controlling sleep stage-specific cellular activity is unknown but this mechanism is possibly governed by only a few nerual systems. Our strategy is to use the dorsal lateral geniculate nucleus (dLGN) as a model for the study of the influence of monamine systems on unit discharge frequencies in different states. By selective removal of the neurochemically well delineated afferents to dLGN one at a time, we can determine the influence of each system. We propose to initiate this investigation by first examining the influence of the locus coeruleus noradrenergic system and the midline raphe serotonergic system. A bilaterally implanted microwire-cannula technique will be employed that allows electrophysiological recording of multiple unit activity of geniculate neurons during sleep and waking and, additionally, permits infusion of drugs into the population of cells under study. Intracerebral infusion of specific neurotoxins will be utilized to achieve local and specific lesions of two monoaminergic geniculate afferents; 6-hydroxydopamine for norepinephrine and 5,7-dihydroxytryptamine for serotonin. Bichemical assays will be used to determine the effectiveness of the drug manipulations. The results should not only provide better understanding of the mechanisms underlying normal sleep behavior but may yield insights into the pathophysiology of abnormal sleep conditions.
NIH ExPorter
NIH ExPorter