NEUROPHYSIOLOGICAL MECHANISMS OF SLEEP CYCLE CONTROL

点击翻译按钮获取中文摘要

Investigation of the triggering mechanism for rapid eye movement (REM) sleep indicates that this behavioral state is produced by the activation of a distributed neuronal network in the paramedian pontine brain stem which leads to the subsequent recruitment of many other neuronal populations throughout the brain. Using single-cell recording, neuronal connectivity mapping, and microinjection pharmacology techniques, considerable progress in delineating the triggering neuronal circuitry of REM sleep has been made but its long term regulation and functional consequences remain obscure. We have recently discovered that exogenous cholinergic stimulation of the endogenous cholinergic peribrachial pontine tegmentum (PbN) with a single microinjection of carbachol produces a two phase response: phase I consists of ipsilateral ponto-geniculo-occipital (PGO) waves which persist for 24 hrs without affecting the pattern and amount of REM sleep; phase II consists of a delayed increase in the number of REM sleep periods that causes a 300% increase in the total amount of REM sleep per day and keeps this REM% significantly elevated for 6-10 days. This proposal describes the several ways in which we plan to follow up on this surprising discovery. First, we will map and characterize discharge properties of cells in the PGO/long-term REM enhancement zone and analyze PbN/PGO burst and tonic neurons in relation to eye movement in waking and in REM both before and during carbachol activation of the PbN to determine the timing relations in both states. Second, we will use other cholinergic agonist and antagonist drugs to determine the neuropharmacological responsiveness of this restricted region in terms of PGO wave triggering and long-term REM enhancement. Third, we will estab- lish the neurochemical identity and connectivity of the PGO/long-term REM enhancement zone in the PbN region with the short-latency REM induction site in the paramedian reticular formation (PRF) to determine if they are reciprocal.