A GABAergic mechanism is necessary for coupling dissociable ventral and dorsal regional oscillators within the circadian clock

Abstract

Background: Circadian rhythms in mammalian behavior, physiology, and biochemistry are controlled by the central clock of the suprachiasmatic nucleus (SCN). The clock is synchronized to environmental light-dark cycles via the retino-hypothalamic tract, which terminates predominantly in the ventral SCN of the rat. In order to understand synchronization of the clock to the external light-dark cycle, we performed ex vivo recordings of spontaneous impulse activity in SCN slices of the rat.

Results: We observed bimodal patterns of spontaneous impulse activity in the dorsal and ventral SCN after a 6 hr delay of the light schedule. Bisection of the SCN slice revealed a separate fast-resetting oscillator in the ventral SCN and a distinct slow-resetting oscillator in the dorsal SCN. Continuous application of the GABA(A) antagonist bicuculline yielded similar results as cut slices. Short application of bicuculline at different phases of the circadian cycle increased the electrical discharge rate in the ventral SCN but, unexpectedly, decreased activity in the dorsal SCN.

Conclusions: GABA transmits phase information between the ventral and dorsal SCN oscillators. GABA can act excitatory in the dorsal SCN and inhibits neurons in the ventral SCN. We hypothesize that this difference results in asymmetrical interregional coupling within the SCN, with a stronger phase-shifting effect of the ventral on the dorsal SCN than vice versa. A model is proposed that focuses on this asymmetry and on the role of GABA in phase regulation.