Paraventricular-subparaventricular hypothalamic lesions selectively affect circadian function.

Abstract

The circadian timing system has three principal components: (i) entrainment pathways, (ii) pacemakers, and (iii) efferent pathways from the pacemakers that convey the circadian signal to effector systems. The suprachiasmatic nucleus (SCN) of the hypothalamus is the principal mammalian circadian pacemaker and, although we understand the organization of entrainment pathways to the SCN and the pacemaker itself, we know much less about the functional organization of SCN projections mediating control of effector systems. It is unclear, for example, whether specific subsets of SCN projections control specific effector systems. In this study, we analyzed the effects of lesions ablating the paraventricular hypothalamic nucleus (PVH), with variable extension into the subparaventricular zone (SPVZ) and adjacent structures, on nocturnal pineal melatonin production and rhythms in core body temperature (Tb) and rest-activity (R-A). In accordance with prior work, ablation of the PVH abolishes the nocturnal rise in pineal melatonin. Lesions restricted to the PVH do not affect rhythms in Tb and R-A but lesions extending caudally and ventrally into the SPVZ disrupt the R-A rhythm proportionate to the interruption of caudal SCN projections without affecting the rhythm in Tb. We conclude that pacemaker regulation of the circadian rhythms analyzed in this study is mediated by discrete sets of SCN projections: (i) dorsal projections to the PVH control pineal melatonin production; (ii) rostral projections to the anterior hypothalamic/preoptic areas mediate the Tb rhythm; and (iii) caudal projections to the SPVZ and hypothalamic arousal systems located in the posterior and lateral hypothalamic areas control the rhythm in R-A.