THE SYNAPTIC BASIS OF SLEEP CYCLE CONTROL

发现睡眠周期中的突触机制

To discover the synaptic mechanisms operating during the sleep cycle and responsible for control of various aspects of the rapid eye movement (REM) or desynchronized (D) phase of sleep, I propose to do intracellular recordings in medial pontine reticular formation (mPRF) neurons during naturally occurring sleep-waking cycles in unanesthetized, undrugged cats. Physiological identification and characterization of neurons will be made by correlation of the intracellular recordings with both electrographic data of the sleep cycle (i.e., EEG, EMG, EOG records) and with the effects of microstimulation-induced post-synaptic potentials and antidromic activation from sites located in the mesencephalic, bulbar and contralateral pontine reticular formation and in the locus coerulus and dorsal raphe nucleus. Identification of morphological characteristics of neurons associated with particular physiological properties will be made through HRP injections into neurons intracellularly recorded in the naturally sleeping cat. These studies will address several questions of fundamental importance to knowledge of how the brain controls its excitability during the sleep-wake cycle: Are there D-specific changes in the mPRF suggestive of an involvement of this region in generation of some D phenomena and perhaps of initiation of the state itself, and, if so, what are the mechanisms of these changes? Do our initial findings of D-specific changes of tonic membrane depolarization, decreased membrane input resistance, and increased excitability apply to all cell types and areas in PRF? Is one mechanism for these alterations disinhibition by biogenic-amine containing cells in the locus coeruleus and dorsal raphe? Does a recently discovered dorso-rostral zone of inhibitory input to mPRF neurons play an important role in PGO wave generation and other D phenomena? Do cells in the most medial portion of mPRF initiate PGO waves? Answers to these questions have broad implications for psychiatry, where knowledge of mechanisms of brain state regulation is basic for this field, but where there are few studies in naturally behaving vertebrates. The now well-known correlation between D sleep abnormalities and endogeneous depression suggests a specific link between aspects of pysiological control mechanisms important in affective disorder and in D. These studies are also relevant to the study of sleep disorders, especially narcolepsy, and to the use in psychiatry of the dream state as a model for psychosis.