Role of neuronal membrane events in circadian rhythm generation.

Circadian clock systems are composed of an input or "entrainment" pathway by which synchronization to the external environment occurs, a pacemaker responsible for generating rhythmicity, and an output or "expression" pathway through which rhythmic signals act to modulate physiology and behavior. The circadian pacemaker contains molecular feedback loops of rhythmically expressed genes and their protein products, which, through interactions, generate a circa 24-h cycle of transcription and translation of clock and clock-controlled genes. Neuronal membrane events appear to play major roles in entrainment of circadian rhythms in mollusks and mammals. In mammals, the suprachiasmatic nuclei of the hypothalamus receive photic information via the retinohypothalamic tract. Retinal signals, mediated by glutamate, induce calcium release and activate a number of intracellular cascades involved in photic gating and phase shifting. Membrane events are also involved in rhythm expression. Calcium and potassium currents influence the electrical output of pacemaker neurons by altering shape and intervals of impulse prepotentials, afterhyperpolarization periods, and interspike intervals, as well as altering membrane potentials and thereby shaping the spontaneous rhythmic spiking patterns. Unlike the involvement of membrane events in circadian entrainment and expression, it is less clear whether electrical activity, postsynaptic events, and transmembrane ion fluxes also are essential elements in rhythm generation. Studies, however, suggest that neuronal membrane activity may indeed play a crucial role in circadian rhythm generation.