There has been substantial progress in understanding the cellular basis of circadian rhythmicity. Advances, to a large extent, have been accomplished through the use of invertebrate models, preparations which exhibit the general properties of vertebrate circadian systems but which allow for a cellular level of analysis. The marine mollusc, Bulla, is proving to be an exceptional preparation for addressing two fundamental questions about circadian systems: 1) the cellular mechanisms governing entrainment, generation and expression of circadian oscillations, and 2) the mechanisms by which pacemakers interact in a multioscillator ensemble (circadian organization). Previous work in our laboratory demonstrates that the Bulla eye expresses a circadian rhythm in optic nerve impulse frequency which is generated by neurons at the base of the retina. These neurons exhibit a circadian rhythm in membrane potential and the phase of this rhythm can be shifted by altering the transmembrane potential. In addition, the two ocular pacemakers are coupled to one another via ocular-derived efferent impulses which depolarize pacemaker neurons. We propose to continue with our study of the Bulla retina and have four major objectives: 1) we wish to continue to identify processes in the entrainment pathway, 2) evaluate the role of changes in specific membrane ionic conductances in expression of the membrane potential rhythm, 3) determine whether individual basal retinal neurons are competent circadian pacemakers and 4) further characterize mechanisms subserving coupling of the two ocular pacemakers. The cellular basis of individual circadian oscillators and the ensemble properties of a multioscillator system represent two fundamental issues in biological timing research.
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