There has been substantial progress towards understanding the physiological basis of circadian rhythmicity. These advances have been made, in large part, through the use of invertebrate models, preparations which display the formal properties of vertebrate circadian systems, but which allow for a cellular level of analysis. The marine mollusc, Bulla, is proving to be a premiere preparation for addressing two fundamental questions about circadian systems: 1) the cellular mechanisms governing the entrainment and generation of circadian rhythmicity, and 2) the mechanisms by which circadian pacemakers interact (circadian organization). Our previous work has demonstrated 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 which can be phase shifted by treatments which depolarize the membrane. In addition, the circadian pacemakers in the two eyes are coupled to one another via efferent optic nerve fibers. This mutual coupling alters the free-running period of the coupled system and can be studied in vitro. We intend to continue our study of the Bulla retina and have two major goals: 1) we wish to explore the role of transmembrane potential and ionic conductances in the entrainment and generation of circadian rhythms within retinal neurons, and 2) we wish to quantitatively analyze the pathways which couple the ocular circadian pacemakers in both Bulla and Bursatella, another opisthobranch with coupled ocular pacemakers. We intend to develop a model for entrainment of circadian pacemakers by neural impulses. Such a framework has utility for understanding the process of entrainment in mammalian circadian systems where a hypothalamic pacemaker is entrained via neural input from the eyes.
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