Regional and laminar differences in synaptic localization of NMDA receptor subunit NR1 splice variants in rat visual cortex and hippocampus

Abstract

Changes in N-methyl-D-aspartate (NMDA) receptor expression may represent a molecular substrate for differences in synaptic plasticity between early postnatal and adult brains (Fox and Zahs [1994] Curr. Opinion Neurobiol. 4:112-119). We have, therefore, examined the regional and laminar distribution of NR1, the essential subunit of the NMDA receptor, in two regions in which synaptic plasticity has been most thoroughly studied: primary visual cortex and hippocampus. To study NR1 expression at the light and electron microscopic levels we have used a new antiserum (NR1-C1; Sheng et al. [1994] Nature 368:144-147) directed against a differentially spliced C-terminal exon ("C1"). The most striking result was that the pattern of NR1-C1 labeling in the adult was more restricted than that of previously published NR1-specific antibodies. Specifically, NR1-C1 did not label cells in the CA3, dentate gyrus or subicular regions of the hippocampus or in layer 4 of the visual cortex. Quantitative ultrastructural analysis revealed that these differences were paralleled by differential expression of NR1-C1 at synapses. In sharp contrast to the pattern in the adult, NR1-C1 immunoreactivity was distributed more widely in the developing brain. At postnatal day 11, NR1-C1 splice variants were expressed in all layers of the visual cortex and in all regions of the hippocampus. The transient expression of NR1-C1 splice variants in layer 4 of visual cortex suggests that NR1-C1 may play a role in determining the critical period for binocular plasticity. Continued expression of NR1-C1 in upper and lower layers of the adult cortex and in CA1 of the hippocampus may provide a substrate for plasticity in corticocortical connections and Schaffer collateral synapses beyond the critical period. In addition to abundant postsynaptic staining, NR1-C1 immunoreactivity was found in a large number of axon terminals in the dorsal subiculum, but in very few terminals in visual cortex. This strongly suggests that presynaptic NMDA receptors play a major role in neuronal processing of hippocampal output through the subiculum, but play a relatively minor role in visual processing.

Distribution of NMDA receptor subunit NR1 in Arctic ground squirrel central nervous system

“…Slight differences in the relative level of staining in some brain regions between AGS and rats were observed. For example, we found equally dense staining in CA1, CA3, dentate gyrus, and hilus regions in AGS hippocampus while, in rats, others have found denser staining in CA1 and CA3 (Petralia et al, 1994) or in CA1 and the hilus region of the dentate gyrus (Johnson et al, 1996). These disparities may be due to strain or species differences or to a difference in antibodies used.…”

“…Localization of NR1 reflects localization of the majority, if not all, NMDAR complexes (Forrest et al, 1994;Sakimura et al, 1995;Nakanishi, 1992). The purpose of this study was, therefore, to characterize the distribution of NR1 subunits in the central nervous system of Arctic ground squirrels (AGS, Spermophilus parryii) using a NR1 antibody, which has been well characterized in rats and other species such as mouse, monkey, and human (Johnson et al, 1996;Bilak et al, 1995;Siegel et al, 1994;Huntley et al, 1994).…”

Differential Dependence of LTD on Glutamate Receptors in the Auditory Cortical Synapses of Cortical and Thalamic Inputs

“…8). In the visual cortex, mGluR5 is present in layers where thalamic fibers terminate (Reid et al 1995), while NMDARs or the NR1 subunit are primarily concentrated in superficial layers (Johnson et al 1996;Rosier et al 1993). These reports suggest that mGluR5 is present mainly at thalamo-cortical synapses, while NMDARs are at cortico-cortical synapses.…”

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).…”