Brain Research, 624 (1993) 347-353 347 © 1993 Elsevier Science Publishers B.V. All rights reserved 0006-8993/93/$06.00 BRES 25856 Organization and quantitative analysis of kainate receptor subunit GIuR5-7 immunoreactivity in monkey hippocampus Paul F. Good a, George W. Huntley a, Scott W. Rogers b, Stephen F. Heinemann c, John H. Morrison a,. a Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, N Y 10029, USA, b Department of Pharmacology, University of Colorado Health Science Center, Denver, CO 80262, USA, c Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA (Accepted 6 July 1993) Key words: Excitatory amino acid; Glutamate receptor; Primate; Confocal microscopy;Quantitative neuroanatomy; Neurodegeneration A monoclonal antibody specific for GIuR5-7 (mAb-4F5) has been used to characterize the distribution of kainate class glutamate receptor subunits in monkey hippocampus. Immunolabeled neurons were present in all subfields of the hippocampus as well as the dentate gyrus and subiculum. Quantitative immunofluorescence analysis by confocal microscopydemonstrated differential levels of immunoreactivitysuch that the highest intensities were in neurons within CA1 and subiculum as compared with those within CA3 or dentate gyms. The regional differences in levels of subunit immunoreactivitycorrelate with the relative vulnerability of hippocampal neurons in several neurodegenerative disorders. The hippocampal formation receives highly pro- cessed sensory information from the neocortex, through the entorhinal cortex (ERC), and is likely to mediate the storage of information as long-term memory 34,5°. The anatomic connections which underlie such func- tions form a multisynaptic circuit from the superficial layers of the ERC through hippocampal subfields and subiculum, and return to deep layers of the E R C 37'41'48. Anatomic 36'3s and pharmacologic 12,1s,26,4° studies have demonstrated that glutamate is the predominant exci- tatory neurotransmitter in the hippocampus but the glutamate receptor composition of each synaptic link has yet to be defined at the cellular and subcellular level of resolution. Molecular biological techniques have demonstrated that the non-N-methyl-o-aspartate (non-NMDA) iono- tropic glutamate receptors are composed of distinct subunit proteins. Such subunits are thought to be as- sembled into functional pentameric receptor com- plexes, in which subunits GluR1-4 appear to represent the major pharmacologically defined a-amino-3-hy- droxy-5-methyl-4-isoxazole-propionic acid (AMPA) re- ceptors s'15'21, while subunits GIuR5-7 3,4,9, and the kainate-binding proteins KA1 and KA2 14"46, appear to represent the major pharmacologically defined kainate receptors although the actual subunit stoichiometries are unknown. The molecular characterization of these subunits has provided an opportunity to develop a precise glutamate receptor profile for defined sets of neurons and the related sequential synaptic links that form the major hippocampal circuits. Such analyses may be a critical component in under- standing the cellular properties underlying the vulnera- bility of hippocampal neurons to the effects of epileptic seizures 2'47 and kainic 27,33 and domoic acid 39 poisoning as well as in the heightened susceptibility of CA1 neurons to hypoxia/ischemia 2°,3°,49 and degenerative processes of Alzheimer's disease 1,6,29. Activation of kainate receptors is thought to play a role in seizure-in- duced damage to the hippocampus as well as in kainate/domoate toxicity while activation of NMDA receptors may be responsible for the acute phase of hypoxic/ischemic changes since they can mediate Ca 2÷ flux 8'31'32. However, it has been shown recently that both classes of ionotropic non-NMDA receptors also mediate Ca 2÷ flux under certain conditions ~°,42 and *Corresponding author. Fax: (1X212)996-9785.