Suprachiasmatic pacemaker organization analyzed by viral transynaptic transport.

The suprachiasmatic nucleus (SCN) of the hypothalamus, the principal circadian pacemaker, is a paired structure with two subdivisions, a ventral core receiving photic input and a dorsal shell receiving non-photic input. Rhythmicity is thought to be generated by individual SCN neurons which are coupled to achieve synchrony [D.K. Welsh, D.E. Logothetis, M. Meister, S.M. Reppert, Individual neurons dissociated from rat suprachiasmatic nucleus express independently phased circadian firing patterns, Neuron, 14 (1995) 697-706]. Normally, the core and shell, and the nuclei on each side, act in unison to transmit rhythmicity to effector systems. It is not known how coupling between neurons in the two subdivisions, and between the two SCNs, takes place. In the present study, we analyze the intrinsic, commissural, and efferent projections of the SCN using the swine herpesvirus (pseudorabies virus, PRV) as a tool for transynaptic analysis of circuits and small iontophoretic injections of the conventional tracer horseradish peroxidase (HRP) conjugated to fluorescein. We find that the core and shell each project through commissural efferents to homologous contralateral areas. The core projects densely to shell but we find little reciprocal innervation. The two subdivisions project to different hypothalamic areas, with the core projecting to the lateral subparaventricular zone and shell to the dorsomedial hypothalamic nucleus and medial subparaventricular zone. These data are the first demonstration that connections within the SCN, and from the SCN to effector regions, are topographically organized and lend insight into the flow of information through and out of the pacemaker.