A Neurophysiological Study of a Lithium-sensitive Phosphoinositide System in the Hamster Suprachiasmatic (SCN) Biological Clock in Vitro

Lithium lengthens the period of free-running circadian rhythms in many species. In mammals the hypothalamic suprachiasmatic nucleus (SCN) has been identified as a biological clock which generates circadian rhythms. The effect of lithium-induced depletion of the intracellular pool of inositol, leading to decreased intracellular second messengers IP3 and DAG, was examined neurophysiologically. Extracellular recordings were obtained from spontaneously discharging SCN neurones maintained in vitro. Superfusion of slices with lithium-containing (0.1-30 mM) aCSF, but not rubidium-containing aCSF, suppressed neuronal firing in a dose-dependent manner. Lithium-induced suppressed firing was reversed by myo-inositol, but not by epi-inositol. These studies provide evidence for basal phosphoinositide turnover in neurones and implicate a lithium-sensitive phosphoinositide system in the maintenance of the spontaneous discharge activity of SCN neurones.