Compartmental origin of the striato-entopeduncular projection in the rat.

The mammalian neostriatum is divisible into neurochemically and cytoarchitectonically distinct striosome and matrix compartments. This compartmentalization is respected by many afferent and efferent projections of the striatum. The distribution of distinct types of neuroactive substances and receptors and the unique connections of the striosome and matrix suggest a functional segregation between these compartments. The present study examines the organization of efferent projections from each of the striatal compartments to the entopeduncular nucleus (EPN), a major output center of the basal ganglia. The fluorescent retrograde tracer fluorogold, or rhodamine-conjugated dextran, was injected into the lateral habenula or the ventrolateral nucleus of the thalamus of adult Wistar rats to identify the topographical organization of EPN-habenular and EPN-thalamic neurons. Fluorogold was then placed into the rostral or caudal parts of the EPN, identified from the previous experiment as areas containing predominantly EPN-habenular or EPN-thalamic neurons, respectively. Sections containing retrogradely labeled neurons in the neostriatum were simultaneously immunolabeled for calbindin-D28kDa, a calcium-binding protein found exclusively in the projection neurons of the matrix. The results indicate that the striatal projection to the EPN-habenular and EPN-thalamic parts of the EPN originates from striosome and matrix neurons, respectively. The duality of striatal outflow involving the EPN suggests a mechanism whereby the striosome is integrated into subcortical pathways that modulate the activity of the basal ganglia via the ascending serotoninergic projection from the dorsal raphe nucleus, whereas the matrix is involved in a loop that includes the thalamus and the cerebral cortex.