Limbic-Basal Ganglia Circuits Parallel and Integrative Aspects

Abstract

Following the pioneering research of Walle Nauta and Lennart Heimer in the seventies of last century, it became increasingly accepted that the basal ganglia, next to motor functions, have an important role in cognitive, emotional, and motivational behavior. The ventral part of the striatum, prominently including the nucleus accumbens, plays a key role in this now well-accepted concept of the basal ganglia functions. The present chapter briefly reviews the early insights and subsequently focuses on the present view on the ‘limbic’ ventral striatum and its distinction from the dorsal striatum (caudate-putamen complex). However, with respect to many features, like cytoarchitecture, connectivity, and histochemical composition, the dorsal and ventral striatum show strong parallels. Distinctive for the ventral striatum are the strong inputs from limbic structures like the basal amygdala, hippocampus, and entorhinal cortex. Furthermore, medial and lateral prefrontal areas project heavily to the ventral striatum. Also subcortical inputs, like those from the ventral tegmental area, raphe nuclei, locus coeruleus, and midline thalamic nuclei, are rather specific for subregions in the ventral striatum. The heterogeneity of the mesencephalic projections, including dopaminergic, glutamatergic, GABAergic, cholinergic, and serotonergic fibers, is being discussed. Like in the dorsal striatum, GABAergic and cholinergic interneurons via their afferents from prefrontal cortex and thalamus form important links in modulating and synchronizing the activity of the medium-size spiny output neurons. The interneurons in the ventral striatum are mostly comparable in their architecture and physiological properties with their counterparts in the dorsal striatum, but there appear to be also some subtle differences. The output of the ventral striatum reaches several basal forebrain structures, like the ventral pallidum, parts of the extended amygdala, lateral preoptic and lateral hypothalamic areas and, finally, different nuclei in the mesencephalon like the ventral tegmental area, substantia nigra, and the midbrain extrapyramidal area. Taking into account the projections from the main target of the ventral striatum, i.e., the ventral pallidum, it is clear that the ‘limbic’, ventral striatum contributes to an extended basal ganglia circuitry that involves the return projections to the prefrontal cortex via various thalamic nuclei, projections to the ventral mesencephalon, potentially influencing the monoaminergic ascending projection systems, as well as a loop through the lateral hypothalamic-lateral habenula circuitry, which has a role in regulating both the dopaminergic and serotonergic cell groups via the GABAergic neurons in the rostromedial tegmental nucleus (RMTg) in the ventral mesencephalon. Finally, some functional aspects and future perspectives are being discussed.