Vasoactive intestinal peptide neurons as synaptic targets for vasopressin neurons in the suprachiasmatic nucleus. Double-label immunocytochemical demonstration in the rat.

Cellular relationships between neurons producing vasopressin or vasoactive intestinal peptide in the suprachiasmatic nucleus of the hypothalamus, the main component of the central circadian timing system in mammals, were investigated in the rat using double immunocytochemistry. Analysis of serial confocal images revealed that the vasopressin-synthesizing neurons not only are important targets for the vasoactive intestinal peptide-synthesizing neurons, as previously demonstrated, but also establish reciprocal axosomatic contacts with these neurons, which have never been reported. On average, 5.4 vasoactive intestinal peptide contacts per vasopressin perikaryon and 1.7 vasopressin contacts per vasoactive intestinal peptide perikaryon were counted. That both types of neurons are linked by reciprocal synapses was confirmed at the electron microscopic level using a combination of immunoperoxidase and immunogold-silver labeling. Existence of an anatomical substrate for a vasopressinergic control of the vasoactive intestinal peptide neurons may have important functional consequences. In view (i) of the presumed, direct or indirect, involvement of the vasopressin neurons in relaying pacemaker information within and outside the suprachiasmatic nucleus, and (ii) of the established role of the vasoactive intestinal peptide neurons as the main light-sensitive cells, it provides support for a neuronal mechanism through which the circadian clock may regulate inputs related to environmental messages. Our electron-microscopic data also extended earlier observations, pointing to the involvement of vasopressin and vasoactive intestinal peptide terminals in so-called double synapses that, conceivably, could regulate neuronal synchronization in the suprachiasmatic nucleus. A morphological basis for non-synaptic interactions that could be involved in ephaptic and/or paracrine communication between both types of peptidergic neurons is also reported.