Chemical anatomy of striatal interneurons in normal individuals and in patients with Huntington's disease

This paper reviews the major anatomical and chemical features of the variou s types of interneurons in the human striatum, as detected by immunostainin g procedures applied to postmortem tissue from normal individuals and patie nts with Huntington's disease (HD). The human striatum harbors a highly ple omorphic population of aspiny interneurons that stain for either a calcium- binding protein (calretinin, parvalbumin or calbindin D-28k), choline acety ltransferase (ChAT) or NADPH-diaphorase, or various combinations thereof. N eurons that express calretinin (CR), including multitudinous medium and a s maller number of large neurons, are by far the most abundant interneurons i n the human striatum. The medium CR+ neurons do not colocalize with any of the known chemical markers of striatal neurons, except perhaps GABA, and ar e selectively spared in HD. Most large CR+ interneurons display ChAT immuno reactivity and also express substance P receptors. The medium and large CR neurons are enriched with glutamate receptor subunit GluR2 and GluR4, resp ectively. This difference in AMPA GluR subunit expression may account for t he relative resistance of medium CR+ neurons to glutamate-mediated excitoto xicity that may be involved in HD. The various striatal chemical markers di splay a highly heterogeneous distribution pattern in human. In addition to the classic striosomes/matrix compartmentalization, the striosomal compartm ent itself is composed of a core and a peripheral region, each subdivided b y distinct subsets of striatal interneurons. A proper knowledge of all thes e features that appear unique to humans should greatly help our understandi ng of the organization of the human striatum in both health and disease sta tes. (C) 2000 Elsevier Science B.V. All rights reserved.