Brain Research 885 (2000) 1–5 www.elsevier.com / locate / bres Research report Regional changes in the hippocampal density of AMPA and NMDA receptors across the lifespan of the rat * Gary L. Wenk , Carol A. Barnes Arizona Research Laboratories, Division of Neural Systems, Memory & Aging, University of Arizona, Tucson, AZ, USA Accepted 2 August 2000 Abstract The current study dissected the fascia dentata (FD) and hilar region from the CA and subicular cell fields of the rat and conducted in vitro determinations of the number of binding sites for N-methyl-D-aspartate (NMDA) and a-amino-3-hydroxy-5-methyl-4-isoxazole 3 3 (AMPA) glutamate receptors across the lifespan.We determined the density of binding of [ H]-glutamate or [ H]-AMPA to NMDA or AMPA receptor sites, respectively. The changes reported might be due to either a change in receptor number or an alteration in the binding characteristics of the receptor site with aging. We found an age-related decline in the number of NMDA receptors in the CA1, CA3 and subicular cell regions of the hippocampus, but not in the FD/hilar region, and an age-related decline in the number of AMPA receptors in the FD/hilar region, but not in the CA fields. The decline in the number of NMDA or AMPA receptors that occurs with aging was not a continuous or homogeneous process. These changes in receptor number might underlie selected age-associated changes in sensitivity to drugs that influence hippocampal function as well as to changes in NMDA-dependent long-term potentiation. A thorough understanding of the mechanisms underlying changes in glutamate receptor function in discrete brain regions, using combined neurochemical and electrophysiological methods, may ultimately provide insight into the fundamental substrates of age-associated memory disorders related to hippocampal dysfunction.  2000 Elsevier Science B.V. All rights reserved. Theme: Neural basis of behavior Topic: Aging Keywords: NMDA; AMPA; Receptor; Aging; Rodents; Hippocampus 1. Introduction these glutamate receptor subtypes impairs learning and memory performance [17] and can block the induction of Normal aging is associated with a decline in hippocam- long-term potentiation (LTP) in the hippocampus [19]. pal-dependent mnemonic abilities in humans [1], non- While facilitation of the function of these receptor sub- human primates [2] and rodents [4]. Glutamate is an types can enhance memory [24], hyperactivity of these important neurotransmitter at hippocampal synapses and is neurotransmitter receptors may underlie the neurode- known to be critical for normal learning and memory generative changes and decline in hippocampal function processes [8]. Glutamate receptors that are sensitive to associated with aging [20]. Investigations of changes in the either N-methyl-D-aspartate (NMDA) or a-amino-3-hy- number of these receptors in aging populations have droxy-5-methyl-4-isoxazole (AMPA) are involved in produced conflicting results. Laboratories have reported synaptic modification that can be induced in this structure either no change [23] or a decline [7,15,21,25,26] in [7,8] that has been hypothesized to reflect a mechanism of numbers of these receptors within the hippocampus. Much information storage [6,16]. Pharmacological blockade of of this variation may be related to differences in the species or strain investigated [13,15] or the particular ligand used in the binding assays. In addition, the apparent *Corresponding author. Tel.: 11-520-626-2617; fax: 11-520-626- discrepancy might also be related to regional changes in 2618. E-mail address: gary@nsma.arizona.edu (G.L. Wenk). receptor density within the hippocampus. In the present 0006-8993 / 00 / $ – see front matter  2000 Elsevier Science B.V. All rights reserved. PII: S0006-8993(00)02792-X