Gastrin-releasing peptide induces c-Fos in the hamster suprachiasmatic nucleus

The suprachiasmatic nuclei (SCN) contain the dominant circadian pacemaker in the mammalian brain. Retinal illumination at specific circadian phases resets the circadian pacemaker and induces the expression of several transcription factors, including c-Fos, in SCN neurons. Gastrin-releasing peptide (GRP) is made by SCN neurons and exogenous GRP mimics the resetting actions of photic stimuli on behavioural and cellular rhythms. We assessed the effects of microinjection of GRP into the SCN region at three phases of the circadian cycle on c-Fos immunoreactivity (-ir) in this structure. Microinjections of GRP increased levels of c-Fos-ir in the SCN. A distinct pattern of c-Fos-ir was seen following GRP administration in the early subjective night, with immunostaining localized to a dorsolateral region of the SCN. Pre-treatment with a GRP receptor antagonist failed to block GRP-evoked increases in c-Fos-ir and the antagonist alone was found to increase c-Fos-ir in the dorsolateral SCN. These results indicate that a subpopulation of SCN neurons is particularly sensitive to microinjection of GRP; activation of these neurons may be important for GRP's phase-delaying actions. Future studies using GRP receptor antagonists that lack intrinsic agonist activity will be needed to fully evaluate the role of these cells in photic entrainment.