Circadian pacemaker neurons: membranes and molecules

1. A circadian pacemaker is located in the eyes of a variety of marine gastropods, including Aplysia and Bulla. It produces a circadian rhythm in the frequency of spontaneously occurring optic nerve (ON) compound action potentials (CAPs). The circadian pacemaker in Bulla includes a population of 100 retinal pacemaker neurons, that produce the rhythmic CAP output. Intracellular recording from the Bulla pacemaker neurons has yielded new insight into their time-keeping ability. 2. Intracellular injection of Lucifer yellow dye into a single pacemaker neuron results in the spread of dye to several neurons. This dye coupling is presumably mediated by the gap junctions among neurons that are responsible for the synchronous firing of the population of pacemaker neurons and the generation of ON CAPs. 3. The circadian pacemaker in each eye interacts with the paired pacemaker in the contralateral eye. The interaction results in the coordinating firing of CAPs from each eye and in the coordinated phasing of the circadian rhythms of CAP activity generated in each eye. This interaction occurs by reciprocal excitatory chemical synapses. These synaptic receptors occur in the ON as well as in the retinal neuropil and CAP synchrony occurs in the ON as well as in the basal retina. 4. Pacemaker neurons are depolarized by 5-HT and membrane permeable cAMP analogues. The membrane resistance increases during the depolarization suggesting a background potassium current is decreased. 5. The tetrapeptide FMRF-HN2 hyperpolarizes the pacemaker neurons. It reverses the effect of 5-HT and cAMP, suggesting 5-HT and FMRF-NH2 may be acting on the same membrane channel, the S channel.(ABSTRACT TRUNCATED AT 250 WORDS)