The role of Clock in the developmental expression of neuropeptides in the suprachiasmatic nucleus

The suprachiasmatic nucleus (SCN) is the dominant circadian pacemaker in ma mmals. To understand better the ontogeny of mouse SCN and the role of the p acemaker in peptide expression, the authors examined the distribution of ce lls that were immunoreactive for vasopressin (AVP) or vasoactive intestinal polypeptide (VIP) in wild type and Clock mutant mice at two developmental stages. Clock homozygous mice failed to show the dramatic increase in the n umber of VIP-immunoreactive (VIP-ir) neurons from postnatal day 6 (P6) to P 30 that was found in the SCN of wild type mice. The number of AVP-ir neuron s was relatively constant in the postnatal SCN but was significantly reduce d in Clock/Clock mice. The effects of the Clock mutation varied with positi on in the SCN for both peptides. Densitometry of immunolabeled brains indic ated that the Clock mutation reduced AVP expression specifically in the SCN and not in other brain areas. The SCN did not significantly change shape o r size with age or Clock genotype. Taken together, these results indicate t hat the neonatal mouse SCN has its full complement of cells, some of which are not yet mature in their neuropeptide content. Furthermore, the observat ion that; the Clock mutation appears to act on a subset of AVP and VIP cell s suggests heterogeneity within these cell classes in the SCN. J. Comp. Neu rol. 424:86-98, 2000. (C) 2000 Wiley-Liss, Inc.