Crossroads of Limbic and Striatal Circuitry: Hypothalamo-Nigral Connections

Abstract

Despite their invariable coexistence in the mammalian brain, limbic system (hippocampus and amygdala) and corpus striatum (striatum or caudatoputamen, and pallidum or globus pallidus) have long made the impression of being two mutually isolated neural mechanisms. Until about twenty-five years ago, these two major components of the forebrain seemed to lack any direct interconnection; for an even longer time they appeared to have no common sources of afferent supply, and their respective efferent fiber pathways until very recently, seemed to have no points of convergence anywhere along their course. To be more specific: until about twenty years ago, known or suspected neocortical afferents to the limbic system were limited to the cingulo-hippocampal connection suggested by Cajal (1911) and later by Papez (1937), whereas cortical afferents to the corpus striatum were generally believed to originate largely or even entirely from the sensorimotor cortex; neither were any other sources of afferents known to be shared by limbic system and corpus striatum. As to the efferent connections of these two forebrain mechanisms: those of the corpus striatum until only a few years ago were thought to be distributed exclusively to the substantia nigra, subthalamic nucleus, centrum medianum and VA-VL complex of the thalamus, and to certain mesencephalic regions (see Nauta and Mehler, 1966, for a review). In none of these distributions did the projections of the corpus striatum seem to overlap the efferents of the limbic system. The latter, instead, have been traced to the anterior and mediodorsal nuclei of the thalamus, as well as to the subcortical continuum formed by the septum, preoptic region and hypothalamus, and extend caudally beyond the hypothalamus over the ventral tegmental area throughout the paramedian region of the midbrain, partly by way of the medial forebrain bundle, partly also by a more dorsal route composed of the stria medullaris, habenular nuclei, and fasciculus retroflexus. It is important to note that a substantial second component of the medial forebrain bundle deviates laterally from the main bundle and distributes itself largely to more lateral regions of the midbrain tegmentum (see below).