Regional, cellular, and ultrastructural distribution of N-methyl-D-aspartate receptor subunit 1 in monkey hippocampus.

Abstract

The regional, cellular, and subcellular distributions of N-methyl-D-aspartate (NMDA) receptor subunit 1, NMDAR-1, were investigated in monkey hippocampus by using a monoclonal antibody directed against a fusion protein corresponding to aa 660-811 of NMDAR-1. The data indicate that many neurons in each subfield of the hippocampus contain NMDAR-1 protein, although the intensity and distribution of immunoreactivity varied across regions, strata, and cellular compartments. In stratum lucidum of CA3, mossy fiber axons were immunoreactive for NMDAR-1, which may correspond to previously hypothesized presynaptic receptors. NMDAR-1-labeled postsynaptic profiles were present in stratum radiatum of CA3 but were largely absent from stratum lucidum. Such intraneuronal segregation of glutamate receptor subunits or classes may be spatially correlated with afferent systems that exhibit laminar segregation and terminate in different portions of the postsynaptic dendritic tree. For example, in CA3 pyramidal cells, NMDA receptors are postsynaptic in distal apical dendrites (stratum radiatum), where NMDA-dependent longterm potentiation in rats is mediated by associational/commissural afferents, and are absent from proximal apical dendrites (stratum lucidum), where NMDA-independent longterm potentiation is mediated by the mossy fiber input.Excitatory neurotransmission in the central nervous system is thought to be largely mediated by the excitatory amino acids glutamate and aspartate through their effects at pre-and postsynaptic receptors (1). The molecular, physiological, and structural characteristics of various excitatory amino acid receptors have been recently reviewed (2-4) and therefore will not be comprehensively described here.The function and distribution of putative postsynaptic N-methyl-D-aspartate (NMDA) receptors have been investigated in numerous physiological, pharmacological, and in situ-hybridization studies (for review, see refs. 2 and 5); however, presynaptic NMDA receptors are also proposed to exist (6). Although, several immunohistochemical studies have recently been published on the distribution of non-NMDA-receptor subunit proteins (7-12), the cellular and synaptic distribution of the NMDA subunit proteins has yet to be characterized in detail. Such data will be crucial to the development of a precise anatomical framework for the role of NMDA receptors in synaptic transmission, long-term potentiation (LTP), and the synaptic interactions between NMDA and non-NMDA-receptor classes.LTP, a potential early step in the cellular mechanism for learning (13), has been induced in various subfields of the hippocampus in rats-including region CAl via stimulation of Schaffer collaterals, region CA3 via mossy fiber and associational/commissural fiber stimulation, and in dentate gyrus granule cells after stimulation of the perforant path (14).The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §17...

NMDA Receptor Heterogeneity During Postnatal Development of the Rat Brain: Differential Expression of the NR2A, NR2B, and NR2C Subunit Proteins

“…Purkinje, stellate/basket, or Bergmann glia cells The time course of expression and signal intensities (Watanabe et al, 1994;Luque and Richards, 1995 fibers may indicate the presence of presynaptic NMDA receptors, the existence of which has recently also been reported in the hippocampus, amygdala, and visual cortex (Aoki et al, 1994;Siegel et al, 1994;Farb et al, 1995;Gracy and Pickel, 1995;Wang and Thukral, 1996). A striking delay in the emergence of the NR2A subunit protein was observed in the hippocampal formation from PU to PlO.…”

Role of a Hippocampal Src-Family Kinase-Mediated Glutamatergic Mechanism in Drug Context-Induced Cocaine Seeking

“…NMDARs are mostly postsynaptic in the hippocampus (Nyiri et al, 2003;Takumi et al, 1999), and have a greater expression of NR2B subunits than other NMDA subunits (ie, NR2A) in the CA1 subregion, but not in the CA3 subregion or the dentate gyrus (Coultrap et al, 2005;Pandis et al, 2006). Also, within the CA1 subregion, NMDAR subunit composition and density vary across cell types (Angulo et al, 2004;Nyiri et al, 2003;Serrano et al, 2006;Serrano et al, 2008;Siegel et al, 1994;Szabadits et al, 2011;Todd et al, 2006;Xue et al, 2011). Thus, given the functional heterogeneity of hippocampal NMDAR populations (Kesner, 2007;Lee et al, 2003), future studies will be necessary to dissect the role of distinct NR2B subunitcontaining NMDAR subpopulations within the DH in drug context-induced cocaine-seeking behavior.…”

Identification of the SNARE complex mediating the exocytosis of NMDA receptors

“…As the neurons mature, the abundance of NR1-NR2A and NR1-NR2A-NR2B heteromers increased (1). Electrophysiological and immunocytochemical evidences showed that in mature neurons, NMDA receptors primarily clustered at excitatory synapses, which were localized on dendritic spines (2)(3)(4)(5)(6)(7)(8). To achieve this specific distribution, NMDA receptors undergo regulations in various trafficking steps, including de novo exocytosis, endocytosis, recycling, lateral movement between synaptic and extrasynaptic membranes, and stabilization by synaptic scaffolding proteins (1,9).…”