Immediate-early genes and the neural bases of photic and non-photic entrainment.

Abstract

The expression of immediate-early genes (IEGs) within the mammalian suprachiasmatic nucleus (SCN) identifies individual light-responsive cells of the circadian system. Cells immunoreactive for products of IEGs form a neurochemically heterogeneous population, of which a few are VIP (vasoactive intestinal peptide)-immunoreactive or GRP (gastrin-releasing peptide)-immunoreactive, although the phenotypes of most of the others have yet to be determined. Dual-labelling experiments with anatomical tracers reveal that only a minority of efferent projection neurons of the SCN are immunoreactive for IEG products, and it is likely that the majority of the immunoreactive cells are interneurons or glia. Photic induction of IEGs is mediated via NMDA (N-methyl-D-aspartate) and non-NMDA glutamatergic receptors, the SCN expressing a topographically specific complement of subtypes of the NMDA receptor. Non-photic cues (arousal) can shift the clock but this is not associated with expression of IEGs, demonstrating that the proteins encoded by IEGs are probably involved in transducing photic cues, rather than shifting the clock per se. Their induction provides an anatomically explicit marker for circadian phase and photic sensitivity and so is useful in analyses of circadian function, for example, in the tau mutant hamster. Non-photic phase shifts are accompanied by adrenocortical activation, confirming the importance of arousal in shifting of the clock. The phase-shifting effect of arousal can be blocked by treatment with the serotonin receptor antagonist ketanserin, suggesting that ascending serotonergic input to the forebrain, possibly directly to the SCN, is an important mediator of entrainment by arousal.