Unwinding the Snail's Clock: Cellular Analysis of a Retinal Circadian Pacemaker

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The eye of the cloudy bubble snail, Bulla gouldiana, expresses a circadian rhythm in spontaneous optic nerve impulse frequency. The circadian rhythm is generated among a group of approximately 100 neurons (basal retinal neurons - BRNs) at the base of the retina. Each BRN appears to be a competent circadian pacemaker. Using the Bulla retina as a model pacemaker system our laboratory has addressed three central issues of circadian physiology: Synchronization: Entrainment of the ocular rhythm to light cycles is mediated by depolarization of pacemaker neurons with a resultant transmembrane calcium flux. Phase shifts of the rhythm are prevented when calcium entry or membrane depolarization is blocked and light-induced phase shifts can be mimicked by depolarization. Depolarization leads to a persistent increase in intraccllular calcium in pacemaker neurons. Expression: The circadian rhythm in impulse frequency is driven by a rhythm in membrane conductance. Membrane conductance is relatively high during the subjective night and decreases by approximately 50 percent near subjective dawn. The 'clock-controlled' conductances are TEA sensitive and recent experiments reveal a circadian modulation in a sustained calcium-inclependent potassium conductance. Rhythm generation: Protein synthesis and transcription appear to play critical roles in rhythm genesis. Alterations in the rates of transcription and translation profoundly affect the velocity of the circadian pacemaker in a phase-dependent manner. Transmembrane ionic fluxes, while not involved in rhythm generation, play critical roles in pacemaker synchronization and rhythm expression.