Regional and laminar differences in synaptic localization of NMDA receptor subunit NR1 splice variants in rat visual cortex and hippocampus.
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.
Johnson
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Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis Missouri 63110, USA.
Jiang
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X
Burkhalter
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A
D017398:Alternative Splicing / Q000502:physiology*; D000818:Animals; D006624:Hippocampus / Q000737:chemistry*; D016253:Microscopy, Immunoelectron; D009474:Neurons / Q000737:chemistry / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis / Q000235:genetics* / Q000648:ultrastructure; D013569:Synapses / Q000737:chemistry / Q000648:ultrastructure; D014793:Visual Cortex / Q000737:chemistry*
D016194:Receptors, N-Methyl-D-Aspartate