Cellular levels of messenger ribonucleic acids encoding vasoactive intestinal Peptide and gastrin-releasing Peptide in neurons of the suprachiasmatic nucleus exhibit distinct 24-hour rhythms.

There is strong evidence supporting the view that the Suprachiasmatic nucleus (SCN) functions as a circadian clock; however, the neural and molecular events underlying SCN function remain unclear. A specific subpopulation of neurons within the ventrolateral aspect of the SCN that contains three peptides, vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI) and gastrin-releasing peptide (GRP), play an important role in SCN function. VIP-containing neurons of the SCN receive synapses from photic projections, and co-injection of all three peptides mimics the phase-delaying effects of light on circadian activity rhythms. In principle, the signaling potential of a neuron containing several transmitters may be affected by the concentration ratio of co-released factors; hence, one mechanism by which VIP/PHI/GRP-containing neurons could influence SCN function is by changing the concentration ratio of these peptides throughout the light-dark cycle. The present study was performed to examine this possibility. Relative cellular levels of mRNA encoding both VIP/PHI and GRP were determined within the SCN every 4 h in rats housed in a 14 h light: 10 h dark cycle. Quantitative in situ hybridization revealed a statistically significant (P<0.005) 24-h profile of changes in VIP/PHI mRNA that peaked during the dark phase, and a significant (P<0.005) 24-h profile of changes in GRP mRNA that peaked during the light phase. These data support the interpretation that cellular levels of mRNAs encoding VIP/PHI and GRP within the SCN exhibit distinct profiles of changes throughout the light-dark cycle. Further, these findings are consistent with the hypothesis that the concentration ratio of VIP and PHI to GRP changes over the light-dark cycle, and that this may be an important mechanism by which circadian rhythms are generated or entrained.