NEUROPHYSIOLOGICAL BASIS OF CIRCADIAN ORGANIZATION

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During the past decade steady progress has been made in our understanding of the physiological basis of circadian rhythms. To a large extent, advances have been achieved through the use of invertebrate models - preparations which display the formal properties of vertebrate circadian systems but which allow for cellular level analysis. Aplysia, a gastropod mollusc, has been an important invertebrate model, primarily due to the presence of a precise circadian pacemaker located within each eye. Nevertheless, the Aplysia preparation suffers from some important weaknesses including the presence of numerous small cells within the retinae and the lack of a robust free-running locomotor rhythm. Through a survey of marine gastropods, we have determined that the ocular pacemaking property is relatively widespread. One opisthobranch, Bulla gouldiana, holds particular promise since it exhibits an extremely clear locomotor rhythm. In addition, the Bulla retina contains fewer cells than the Aplysia eye and appears particularly well suited for intracellular analysis. We intend to exploit the Bulla preparation in an effort to address two issues. First, we intend to determine whether individual retinal cells are circadian pacemakers or whether long periodicities emerge from cellular interactions. Secondly, we intend to indentify and characterize, functionally and cellularly, the pathways by which the ocular pacemakers interact with each other and with other elements to control rhythmic locomotor behavior. We believe these are two fundamental questions in understanding the functioning of the nervous system.