Journal of Chemical Neuroanatomy 22 (2001) 13 – 42 Ionotropic and metabotropic GABA and glutamate receptors in primate basal ganglia Yoland Smith a,b, *, Ali Charara a , Maryse Paquet a , Jeremy Z. Kieval a , Jean-Franc ¸ois Pare ´ a , Jesse E. Hanson a , George W. Hubert a , Masaaki Kuwajima a , Allan I. Levey b a Diision of Neuroscience, Yerkes Regional Primate Research Center, Emory Uniersity, 954, Gatewood Rd NE, Atlanta, GA 30322 , USA b Department of Neurology, Emory Uniersity, Woodruff Memorial Building, Suite 6000, PO Drawer V, Atlanta, GA 30322, USA Received 31 July 2000; received in revised form 13 November 2000; accepted 13 November 2000 Abstract The functions of glutamate and GABA in the CNS are mediated by ionotropic and metabotropic, G protein-coupled, receptors. Both receptor families are widely expressed in basal ganglia structures in primates and nonprimates. The recent development of highly specific antibodies and/or cDNA probes allowed the better characterization of the cellular localization of various GABA and glutamate receptor subtypes in the primate basal ganglia. Furthermore, the use of high resolution immunogold techniques at the electron microscopic level led to major breakthroughs in our understanding of the subsynaptic and subcellular localization of these receptors in primates. In this review, we will provide a detailed account of the current knowledge of the localization of these receptors in the basal ganglia of humans and monkeys. © 2001 Elsevier Science B.V. All rights reserved. www.elsevier.com/locate/jchemneu 1. Introduction Although the implication of ‘‘the basal ganglia’’ in the control of motor behaviors has long been known, the exact mechanisms by which these brain regions participate in motor control is still obscure and contro- versial. Furthermore, it is now clear that the functions of basal ganglia extend far beyond mere sensorimotor integration to include major cognitive and limbic com- ponents. The evidence that many neurodegenerative diseases of the basal ganglia often lead to major cogni- tive impairment accompanied by psychiatric problems strongly support the non-motor functions of these brain regions (Brown and Marsden, 1984; Marsden, 1984; Brown and Marsden, 1988; Sano et al., 1989; Mayeux et al., 1990, 1992). Our knowledge of the anatomy and pathophysiology of primate basal ganglia has increased dramatically over the past 20 yr due to the introduction of highly sensitive chemoanatomical methods, brain imaging techniques and the discovery of 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine (MPTP), a chemical which selectively kills midbrain dopaminergic neurons in primates and induces Parkinson’s disease (PD) (Davis et al., 1979; Langston et al., 1983). The MPTP model of PD is one of the best animal model of neurodegenerative diseases currently available. The use of this animal model has led to major breakthroughs in our understanding of the functional circuitry of the basal ganglia and served as the cornerstone for the development of novel surgical and pharmacological therapies for PD (see Starr, 1995; Blandini et al., 1996; Poewe and Granata, 1997; Vitek, 1997 for reviews). The work that has been carried out in our laboratory over the past 10 yr has aimed at understanding various aspects of the connectivity and synaptic organization of the basal ganglia in non-human primates (Smith et al., 1998a,b). The recent development of highly sophisti- cated electron microscopic immunocytochemical ap- proaches allowed us and others to better characterize the subsynaptic and subcellular localization of neuro- transmitter receptors involved in mediating synaptic communication at various GABAergic and glutamater- gic synapses in the primate basal ganglia (Paquet and Smith, 1996; Paquet et al., 1997; Waldvogel et al., 1998; * Corresponding author. Tel.: +1-404-7277519; fax: +1-404- 7273278. E-mail address: yolands@rmy.emory.edu (Y. Smith). 0891-0618/01/$ - see front matter © 2001 Elsevier Science B.V. All rights reserved. PII:S0891-0618(01)00098-9