LOCALIZATION OF IONOTROPIC AND METABOTROPIC GLUTAMATE RECEPTORS IN DISTINCT NEURONAL ELEMENTS OF THE RAT SUBSTANTIA-NIGRA

The localization of glutamate receptors in the substantia nigra is of critical importance since glutamate receptor-mediated excitotoxicity i s implied in the cause for the neuronal degeneration in Parkinson's di sease. The major glutamatergic synaptic inputs to the substantia nigra originate in the subthalamic nucleus, in which hyperactivity is repor ted in Parkinson's disease. In order to compare directly the localizat ion of different ionotropic and metabotropic glutamate receptors in th e substantia nigra of the same animals, rats were perfuse-fixed under deep anesthesia. Sections of the substantia nigra were obtained and re ceptor immunocytochemistry was performed using commercially available antibodies (against subunits of ionotropic glutamate receptors: GluR1, GluR2/3, GluR4, NMDAR1, NMDAR3A/B: and subtypes of metabotropic gluta mate receptors: mGluR1 alpha, mGluR2/3). When compared to the localiza tion of tyrosine hydroxylase immunoreactivity, immunoreactivity for Gl uR1, GluR2/3 and NMDAR1 was mainly localized in the perikarya and prox imal dendrites of the compacta neurons and only in a few reticulata ne urons. In contrast, GluR4 immunoreactivity was only detected in the re ticulata neurons. Consistent results were obtained by double labeling experiments that revealed tyrosine hydroxylase and GluR1, GluR2/3, Glu R4 or NMDAR1 immunoreactivity in the same sections. Immunoreactivity f or NMDAR2A/B, mGluR1 alpha and mGluR2/3 was detected in the neuropil o f the substantia nigra pars reticulata. No NMDAR2A/B- and mGluR2/3-imm unoreactive perikarya were detected. However, a few neurons in the ret iculata were found to be mGluR1 alpha-immunoreactive. The present resu lts indicate there is a differential localization of different subunit s and subtypes of glutamate receptors in the substantia nigra and ther e may be functional implications in different neuronal elements in the substantia nigra in normal and in Parkinson's disease, (C) 1998 Elsev ier Science Ltd. All rights reserved.