STATE DEPENDENT CONTROL OF MOTORNEURON ACTIVITY

University Of California Los Angeles, Los Angeles CA

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Abstract

The clinical signs of a number of sleep disorders are reflected in abnormal patterns of motor behavior. These patterns of behavior are evidenced, for example, during wakefulness by cataplectic attacks, in which the motor inhibition that normally occurs during active (REM) sleep is apparently expressed during the waking state. On the other hand, during active sleep, when there is a lack of motor inhibition, individuals can carry out patterned motor behavior and still remain asleep, for example, in the condition of REM Sleep Behavior Disorder. These and other disorders of sleep that involve either the lack of motor inhibition during sleep or the abnormal expression of active sleep pattern of inhibition during wakefulness (see II. Background and Significance) are the clinical bases for the proposed studies which are organized within the framework of the paradoxical phenomenon of "reticular response-reversal." This phenomenon is based upon the finding that identical stimulation of a specific pontine reticular nucleus (pontis oralis) elicits excitatory postsynaptic potentials in trigeminal motoneurons during wakefulness and quiet sleep, and inhibitory postsynaptic potentials in these same motoneurons during active sleep. We hypothesize that this state-dependent pattern of response-reversal is due to the opening of a "neuronal gate" during active sleep, which results in the nucleus pontis oralis initiating discharge in a site which we discovered in the parvocellular area of the medullary reticular formation. This site appears to be critical for the promotion of the non-reciprocal glycinergic inhibition of trigeminal motoneurons during active sleep. We also hypothesize that neurons of the pedunculo- pontine/laterodorsal tegmental nuclei excite, during active sleep, cells of the nucleus pontis oralis. The research described in this application is designed to elucidate the neuronal circuitry and neurotransmitters which are responsible for the state-dependent modulation of trigeminal motoneuron membrane potential activity during sleep and wakefulness. Interdisciplinary electrophysiological, iontophoretic and morphological studies are proposed, each of which relates to and complements the others. Accordingly, experiments will be undertaken to determine the state- dependent activity of and interrelationships between the trigeminal motor nucleus, a parvocellular site in the medullary reticular formation, the nucleus pontis oralis and the pedunculo-pontine/laterodorsal tegmental nuclei. In addition to examining the circuitry underlying reticular response-reversal, intracellularly-derived data of the membrane potential activity and neurotransmitter sensitivities of these medullary and pontine cell groups in the chronic intact animal will provide important information that, we believe, will significantly advance our understanding of the neuronal control of active sleep and its related pathologies.