Graybiel_1986_Nature_323_625

Acetylcholine and dopamine are key neurotransmitters in the extrapyramidal motor system, where they are thought to lie in a 'functional balance' brought about by interactions between the terminals of the dopamine-containing nigrostriatal tract and the cholinergic interneurones of the striatum. The precise nature of these interactions is not understood, however, nor is it clear how they influence the functioning of striatal systems containing other neurotransmitters. A new clue to understanding such interplay among transmitter-coded systems in the striatum has come from the finding that many of them, including nigrostriatal afferents, follow a macroscopic ordering in which neural elements are concentrated either in or out of the striatal tissue compartments called striosomes. We here report that the cholinergic neuropil of the striatum is also compartmentalized: fibres expressing immunoreactivity to antibodies raised against choline acetyltransferase (ChAT) are sparse in striosomes and are dense in the extrastriosomal matrix. These findings suggest that the interactions between acetylcholine and other neurotransmitters in the striatum are spatially constrained, that cholinergic modulation of striatal function predomintes in the extrastriosomal matrix, and that extrapyramidal pathways originating in the matrix, including transthalamic pathways to the frontal lobes, may in particular reflect this cholinergic influence. Such a differential organization of striatal cholinergic circuitry could help to account for the selective therapeutic efficacy of anticholinergic drugs in the treatment of extrapyramidal disorders.