Distinct gradients of various neurotransmitter markers in caudate nucleus and putamen of the human brain

The caudate nucleus (CN) and the putamen (PUT) as parts of the human striatum are distinguished by a marked heterogeneity in functional, anatomical, and neurochemical patterns. Our study aimed to document in detail the regional diversity in the distribution of dopamine (DA), serotonin, γ‐aminobuturic acid, and choline acetyltransferase within the CN and PUT. For this purpose we dissected the CN as well as the PUT of 12 post‐mortem brains of human subjects with no evidence of neurological and psychiatric disorders (38–81 years old) into about 80 tissue parts. We then investigated rostro‐caudal, dorso‐ventral, and medio‐lateral gradients of these neurotransmitter markers. All parameters revealed higher levels, turnover rates, or activities in the PUT than in the CN. Within the PUT, DA levels increased continuously from rostral to caudal. In contrast, the lowest molar ratio of homovanillic acid to DA, a marker of DA turnover, coincided with highest DA levels in the caudal PUT, the part of the striatum with the highest loss of DA in Parkinson’s disease (N. Engl. J. Med., 318, 1988, 876). Highest DA concentrations were found in the most central areas both in the PUT and CN. We observed an age‐dependent loss of DA in the PUT and CN that did not correspond to the loss described for Parkinson’s disease indicating different mechanisms inducing the deficit of DA. Our data demonstrate a marked heterogeneity in the anatomical distribution of neurotransmitter markers in the human dorsal striatum indicating anatomical and functional diversity within this brain structure. Caudate nucleus (CN) and putamen (PUT) of the dorsal striatum are involved in higher brain functions and part of the extrapyramidal motor system. We demonstrate a pronounced regional diversity in the distribution of dopamine (DA), serotonin, γ‐aminobuturic acid, and choline acetyltransferase, for example, DA levels continuously increase from rostral to caudal PUT, whereas their rostro‐caudal distribution is bell‐shaped in the CN, and the highest levels are associated with the lowest turnover in the most central area of CN and PUT. The described gradients might be relevant for comparing tissue samples from healthy and diseased striatum and directing intrastriatal therapy of diseases. Read the Editorial Highlight for this article on page 623