Narcolepsy is a disease characterized by daytime sleepiness, hypnagogic hallucinations, sleep paralysis and cataplexy. In humans, the symptoms begin to appear at adolescence and continue throughout adulthood, limiting employment and education, and leading to accidents. It has been hypothesized that narcolepsy is a disease of REM sleep regulation and that its principal symptoms represent an """"""""escape"""""""" of REM sleep components into waking. For example, cataplexy and sleep paralysis are hypothesized to represent a triggering of the REM sleep muscle tone suppression mechanism in waking. Drugs that manipulate the cholinergic and noradrenergic systems strongly affect the primary symptoms of narcolepsy, although the side effects of such drugs greatly limit their therapeutic utility. We propose to investigate the changes in neuronal activity underlying cataplexy. We will employ microwire techniques to record from the pedunculopontine (PPN), laterodorsal tegmental (LDT) and locus coeruleus nuclei during cataplectic attacks. These are the principal pontine nuclei implicated in REM sleep control. We will determine the direction and time course of changes in discharge in these cell groups in relation to cataplexy and REM sleep. We will determine how doses of drugs that affect cataplexy alter the activity of each cell type. A better understanding of the circuit underlying cataplexy and the way in which drugs affect the neurons in this circuit would aid in the development of more specific treatments for narcolepsy. It would also shed light on the mechanisms generating REM sleep, controlling muscle tone and regulating arousal.
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