Differential effects of glutamatergic blockade on circadian and photic regulation of gene expression in the hamster suprachiasmatic nucleus

Abstract

Nocturnal light exposure induces immediate-early gene (IEG) expression in the hypothalamic suprachiasmatic nucleus (SCN) and causes phase shifts of activity rhythms in mammals. Some IEGs also show a circadian rhythm of expression in the SCN. While excitatory amino acids (EAAs) are known to be involved in mediating photic regulation of entrainment and gene expression, their involvement in spontaneous rhythms of gene expression has not been studied. We assessed the role of NMDA receptors in the expression of NGFI-A, junB and fosB mRNAs induced by light pulses of different intensities late in the night (Zeitgeber Time [ZT] 18). We also examined the spontaneous expression of junB mRNA near subjective dawn (ZT 0). Both dim (5 lx) and bright (100 lx) light pulses induced similar levels of expression of NGFI-A and junB in the SCN late in the night. fosB mRNA was strongly induced by bright light but was less sensitive to dim light. At ZT 18, dizocilpine (MK-801) (3 mg/kg, i.p.), a non-competitive NMDA receptor antagonist, almost completely blocked light-evoked expression of IEG mRNAs in the ventral SCN but not in the dorsolateral region at a mid-caudal level using either light intensity. At ZT 0, MK-801 strongly reduced light-evoked expression of junB mRNA in both SCN subdivisions, but inhibited spontaneous expression significantly only in the dorsal region. NMDA receptors appear to play an important role in mediating photic input regulating IEG expression only in the ventral SCN at night. At dawn, however, NMDA receptors are involved in mediating photic effects in both parts of the SCN, as well as being involved in spontaneous activation of junB expression selectively in the dorsal SCN. These findings support the idea that the effects in the dorsolateral SCN of nocturnal light exposure are mediated by different mechanisms than those in other portions of the nucleus.