This presentation reviews the major anatomical and chemical features of the various types of neurons in the human striatum, as detected by immunostaining procedures applied to postmortem tissue from normal individuals and patients with Huntington's disease (HD). The human striatum harbors a highly heteromorphic population of aspiny interneurons that stain for a calcium-binding protein (calretinin, parvalbumin or calbindin D-28k), choline acetyltransferase (ChAT) or NADPH-diaphorase, or various combinations thereof. Neurons that express calretinin (CR), including multitudinous medium and a smaller number of large neurons, are by far the most abundant interneurons in the human striatum. The medium CR+ neurons do not colocalize with any of the known chemical markers of striatal neurons, except perhaps GABA, and are selectively spared in HD. Most large CR+ interneurons display ChAT immunoreactivity and also express substance P receptors. The medium and large CR+ neurons are enriched with glutamate receptor subunit GluR2 and GluR4, respectively. This difference in AMPA GluR subunit expression may account for the relative resistance of medium CR+ neurons to glutamate-mediated excitotoxicity that may be involved in HD. The various striatal chemical markers display a highly heterogeneous distribution pattern in human. In addition to the classic striosomes/matrix compartmentalization, the striosomal compartment itself is composed of a core and a peripheral region; each subdivided by distinct subsets of striatal interneurons.
The human striatum also harbors a population of dopaminergic (DA) neurons. Stringent morphological and chemical criteria were used to identify striatal DA neurons, including immunostaining for tyrosine hydroxylase (TH), DA transporter (DAT) and neuronal nuclear protein (NeuN). The most frequent DA neurons had medium-sized (20 um) perikarya with 3-5 varicose dendrites, whereas others had smaller (10-15 um) perikarya with 3-4 varicose dendrites. Additionally, there was a small number (>1%) of larger DA (25-30 um) neurons with spiny dendrites, as well as few neurogliform neurons preferentially located in striatal bridges. Some DA neurons were scattered throughout the striatal matrix, whereas others prevailed in ventral striatum. Despite significant inter-individual variations, the human striatum (mean volume of 8.76 cm3 ) contained a mean of 332 DA neurons. However, this number could have been 10 times higher if the dense ventral striatal clusters observed in 2 brains had been included in the counting. Some striatal DA neurons expressed calretinin, but none stained for DßH, GAD65/67, GABA, calbindin, ChAT, NPY or somatostatin. The striatal DA neurons form a rather unique neuronal population that should not be confounded with some segment of nigrostriatal DA fibers that displayed large (8-15 um) varicosities and looked very much like the small bipolar neurons described in other studies. The possibilities that striatal DA neurons are generated de novo and that their number varies significantly in cases of Parkinson's and Huntington's diseases are currently under investigation.
A proper knowledge of all these features that appear unique to human should greatly help our understanding of the organization of the human striatum in both health and disease states.
[Supported by a grant from the Canadian Institutes for Health Research] | 
