Topographic organization of suprachiasmatic nucleus projection neurons

The mammalian circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN), has two subdivisions. The core is located above the optic chiasm, r eceives primary and secondary visual afferents, and contains neurons produc ing vasoactive intestinal polypeptide and gastrin-releasing peptide. The sh ell largely surrounds the core, receives input from nonvisual sources and c ontains neurons producing arginine vasopressin and calretinin. In this stud y, we tested the hypothesis that SCN efferent projections are topographical ly organized with respect to the subdivision of origin. Injections of retro grade tracers were placed in major sites of efferent termination, described from prior studies that used anterograde tracers (Watts and Swanson, [1987 ] J. Comp. Neurol. 258:230-252; Watts et al. [1987] J. Comp. Neurol. 258:20 4 -229). After retrograde tracer injections in the medial preoptic area, do rsomedial and paraventricular hypothalamic nuclei, bed nucleus of stria ter minalis, para ventricular thalamic nucleus, zona incerta, and medial subpar aventricular zone, retrogradely labeled SCN cells are clustered in the shel l with few labeled neurons in the core. After injections centered in the la teral subparaventricular zone, peri-suprachiasmatic region, lateral septum, or ventral tuberal area, the majority of neuronal label is in the core wit h moderate to sparse neuronal label in the shell. Both subdivisions are lab eled after injections in the paratenial thalamic nucleus. The same pattern of retrograde labeling is found with four tracers, cholera toxin-p subunit, Fluoro-Gold, the Bartha strain of pseudorabies virus, and biotinylated dex tran amine. These data extend our understanding of the significance of the division of the SCN into shell and core by demonstrating that the subdivisi ons differ in the pattern of projections. Together with prior observations that the subdivisions differ with respect to afferents, local connections, and neuroactive substances, the present study provides an anatomic basis fo r discrete control of circadian function by the SCN core and shell. In this novel view, the nature of the signal conveyed to areas receiving core or s hell projections varies as a function of the subdivision from which innerva tion is derived. (C) 2001 Wiley-Liss. Inc.