Functional heterogeneity of the matrix compartment in the cat caudate nucleus as demonstrated by the cholinergic presynaptic regulation of dopamine release

Abstract

Previously, using a new in vitro microsuperfusion procedure, we have demonstrated marked differences in the cholinergic presynaptic regulation of the release of [ 3H]dopamine continuously synthesized from [ 3H]tyrosine in two close striosomal- and matrix-enriched areas of the cat caudate nucleus. A tetrodotoxin-resistant stimulatory effect of acetylcholine mediated by muscarinic receptors was observed in both compartments. However, in addition, two opposing types of tetrodotoxin-sensitive acetylcholine-evoked regulation of [ 3H]dopamine release were only seen in the matrix: one facilitatory, involving nicotinic receptors located on as yet unidentified neurons, and the other inhibitory, mediated by muscarinic receptors located on dynorphin-containing neurons. In the present study, using the same approach, a functional heterogeneity was demonstrated in the matrix. Indeed, in various conditions the effects of acetylcholine (50 μM) on the release of [ 3H]dopamine were different in a matrix-enriched area (matrix 2) distinct from that previously investigated (matrix 1); these areas being characterized by the presence or absence of islands of striatonigral cells, respectively. As in matrix 1, acetylcholine induced a short-lasting stimulation of [ 3H]dopamine release in matrix 2 but, in contrast to that observed in matrix 1, the acetylcholine-evoked response in matrix 2 was not modified in the presence of tetrodotoxin (1 μM). Experiments made in the presence of the tetrodotoxin and atropine (1 μM) indicated that both muscarinic and nicotinic receptors are located on dopaminergic nerve terminals in matrix 2 while muscarinic receptors are only present in matrix 1. In the absence of tetrodotoxin, the short-lasting stimulation of [ 3H]dopamine release was transformed into a long-lasting response in the presence of pempidine (50 μM), in matrix 2 but not in matrix 1 while prolonged responses were seen in both matrix areas in the presence of atropine. Finally, the acetylcholine short stimulatory effect on [ 3H]dopamine release was transformed into a long stimulatory response in the presence of bicuculline (50 μM) but not naloxone (1 μM) in matrix 2 while the reverse was observed in matrix 1. By providing further evidence for a functional heterogeneity of the matrix, our results suggest that depending on the matrix area investigated, dynorphin- or GABA-containing neurons are involved in the indirect cholinergic inhibitory control of dopamine release.