Hypothalamic melanin-concentrating hormone projections to the septo-hippocampal complex in the rat

Melanin-concentrating hormone (MCH) and neuropeptide glutamic acid-isoleucine (NEI) are expressed in neurons that are located mainly in the hypothalamus and project widely throughout the rat central nervous system. One of the main targets of melanin-concentrating hormone is the hippocampal formation, although the exact origin of the projections is unknown. By using injections of the retrograde tracer True Blue into the hippocampus, together with immunohistochemical analysis, we observed retrogradely labeled melanin-concentrating hormone-containing neurons in the lateral hypothalamic area, incerto-hypothalamic area, perifornical area, the periventricular nucleus of the hypothalamus, and in the internuclear area (between the dorsomedial and ventromedial nuclei of the hypothalamus), as well as a few retrogradely labeled and melanin-concentrating hormone-immunoreactive cells in the supramammillary nucleus. The afferents from the lateral hypothalamic area were confirmed using injection of the anterograde tracer biotinylated dextran amine, which enabled us to use histochemical analysis in order to visualize fibers and terminals in the hippocampal formation. In the medial septal nucleus, we found cholinergic neurons that are also putatively innervated by melanin-concentrating hormone immunoreactive fibers and project to the hippocampal formation. Finally, using two different protocols for immunoperoxidase, we were able to show GABAergic basket cells presumably innervated by melanin-concentrating hormone-immunoreactive fibers in the hippocampal formation. On the basis of the data collected herein, we hypothesize that the MCH/NEI projections from hypothalamic nuclei participate in spatial memory and learning through direct and indirect pathways. These pathways would enable the animal to organize its exploratory behavior during foraging.