The general goal of our research is to analyze the mechanism and function of desynchronized (D) sleep at the cellular and molecular levels. Single cell recording and chemical microstimulation techniques will be used separately and, in combination, to test specific hypotheses about the causes and effects of REM sleep in cats. Two mechanistic tenets of the reciprocal interaction hypothesis will be investigated: 1) the proposal that D sleep is maintained by cholinergic activation of a diffuse generator network, but triggered with great anatomical specificity will be investigated by performing microinjection of cholinergic agonists, cholinesterase antagonists and suitable control compounds. We will test the hypothesis that there exists: a) a maximally sensitive zone (or """"""""hot spot""""""""); b) a gradient of sensitivity around that zone and c) a set of still more peripheral sites whose activation leads to dissociation and even suppression of D sleep. 2) the proposal that cessation of DRN firing is actively inhibited and causally related to the increased cholinergic excitatory process (via disinhibition) will be investigated by recording from raphe neurons, and testing their excitability to orthodromic and antidromic stimuli as the natural and chemically simulated REM sleep episodes develop. In these studies, causality will be inferred by the degree of association (vs. dissociation) of raphe activity and specific REM sleep signs including pontine reticular cell-activation curves. The functional hypothesis that REM sleep provides the forebrain with redundant, stereotyped but specific sensorimotor signals will be tested by establishing the cortical neuronal correlates of the recently discovered association between cortical PGO wave amplitude and lateral direction of REM sleep eye movements. Understanding the neurophysiological basis of D sleep generation is an important and strategic step in behavioral neurobiology not only because of its potential impact upon the treatment of sleep disorders but for its bearing upon major psychiatric disabilities such as depression.
