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

J Comp Neurol. 1996 May 6;368(3):335-55. doi: 10.1002/(SICI)1096-9861(19960506)368:3<335::AID-CNE2>3.0.CO;2-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing / physiology*
  • Animals
  • Hippocampus / chemistry*
  • Microscopy, Immunoelectron
  • Neurons / chemistry
  • Neurons / ultrastructure
  • Rats
  • Rats, Inbred Strains / physiology*
  • Receptors, N-Methyl-D-Aspartate / analysis
  • Receptors, N-Methyl-D-Aspartate / genetics*
  • Receptors, N-Methyl-D-Aspartate / ultrastructure
  • Synapses / chemistry
  • Synapses / ultrastructure
  • Visual Cortex / chemistry*


  • Receptors, N-Methyl-D-Aspartate