Differential expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor subunits by calretinin-immunoreactive neurons in the human striatum

We recently reported the existence of medium and large interneurons immunor eactive for the calcium-binding protein calretinin in the human striatum. W e also showed a selective sparing of all medium, but not all large, calreti nin-immunoreactive striatal neurons in Huntington's disease striatum. Becau se glutamate receptor-mediated excitotoxicity has been implicated in the ma ssive loss of striatal projection neurons that characterizes Huntington's d isease, we have applied a double-antigen localization procedure to post mor tem tissue from eight normal human subjects to determine the expression of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate glutamate receptor subunits 1/2/4 by the calretinin-immunoreactive interneurons. The two type s of calretinin-immunoreactive neurons were found to display various patter ns of glutamate receptor subunit expression and a specific regionalization was also noted in the expression of these glutamate receptor subunits. Appr oximately half of the large calretinin-immunoreactive neurons displayed imm unoreactivity for glutamate receptor subunits 1 and 2, and about the same p roportion of medium calretinin-immunoreactive neurons expressed glutamate r eceptor subunits 1 and 4. These double-labeled neurons were rather uniforml y distributed in the caudate nucleus and putamen. In contrast, as much as 7 0.1% of the large calretinin-immunoreactive neurons displayed glutamate rec eptor subunit 4 immunoreactivity in the postcommissural portion of the puta men, an area that corresponds to the sensorimotor striatal territory. For t heir part, the medium calretinin-immunoreactive neurons were markedly enric hed with glutamate receptor subunit 2, 76% of them being double labeled in the caudate nucleus, which corresponds to the striatal associative territor y, compared with 85.5% in the postcommissural putamen. Receptor subunit composition plays a key role in determining the functional properties of glutamate receptors, including their permeability to calcium and susceptibility to excitotoxic insults. Thus, the differential expressi on of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate glutamate recept or subunits reported here may help to explain the selective sparing of cert ain types of calretinin-immunoreactive striatal interneurons in Huntington' s disease, although other factors, such as post-transcriptional editing, ar e also likely to be involved. (C) 1999 IBRO. Published by Elsevier Science Ltd.