Circadian Rhythmicity in AVP Secretion and GABAergic Synaptic Transmission in the Rat Suprachiasmatic Nucleus

Abstract

A variety of physiological and behavioral functions exhibit circadian changes and these circadian rhythms are driven by oscillatory expression of clock genes in the suprachiasmatic nuclei (SCN). It is still unknown how this molecular clockwork is controlled by extracellular neurohormones and neurotransmitters and which membrane receptors undergo circadian modulation. Circadian rhythm can be measured as a secretion of arginine vasopressin (AVP) in organotypic SCN culture for several weeks. Melatonin applied directly to the SCN late in the day induces a phase advance, when applied late at night or at the beginning of the day melatonin causes a phase delay. The time window for phase advance corresponds with the highest level of melatonin receptors in the SCN but the mechanism of melatonin-induced phase delay is unknown. The principal neurotransmitter on SCN synapses is gamma-aminobutyric acid (GABA), which acts at postsynaptic GABA(A) receptors. Spontaneous release of GABA from presynaptic nerve terminals, recorded as miniature inhibitory postsynaptic currents in the presence of TTX, does not change, but zinc sensitivity of exogenous GABA-induced currents varies during the day and night, possibly due to changes in subunit composition of GABA(A) receptors. We conclude that there is daily variation in the postsynaptic, but not presynaptic, function in the SCN.