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Differential contribution of NMDA receptors in hippocampal subregions to spatial working memory

Nature Neuroscience volume 5, pages 162–168 (2002)Cite this article

Abstract

N-methyl-d-aspartate (NMDA) receptor–dependent synaptic plasticity in the mammalian hippocampus is essential for learning and memory. Although computational models and anatomical studies have emphasized functional differences among hippocampal subregions, subregional specificity of NMDA receptor function is largely unknown. Here we present evidence that NMDA receptors in CA3 are required in a situation in which spatial representation needs to be reorganized, whereas the NMDA receptors in CA1 and/or the dentate gyrus are more involved in acquiring memory that needs to be retrieved after a delay period exceeding a short-term range. Our data, with data from CA1-specific knockout mice, suggest the possibility of heterogeneous mnemonic function of NMDA receptors in different subregions of the hippocampus.

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Figure 1: Histologically verified cannula placements for the behavioral experiment (CA3-APV, n = 6; CA3-PBS, n = 7; CA1-APV, n = 4; CA1-PBS, n = 4; DG-APV, n = 4 and DG-PBS, n = 4).
Figure 2: Performance in the familiar spatial environment versus the novel spatial environment.
Figure 3: Performance with variable delays in the familiar room.
Figure 4: Selective inhibition of the LTP induction in CA3 with APV injections into the CA3 subregion.
Figure 5: Sustained blockade of LTP induction in CA3 by APV injection into CA3.

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Acknowledgements

This work was supported by the Human Frontier Science Program and NSFIBN 9817583.

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Authors and Affiliations

  1. Program in Neuroscience, University of Utah Medical Center, 50 North Medical Drive, Salt Lake City, 84132, Utah, USA

    Inah Lee & Raymond P. Kesner

  2. Department of Psychology, 390S 1530E Room 502, University of Utah, Salt Lake City, 84112, Utah, USA

    Raymond P. Kesner

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Correspondence to Raymond P. Kesner.

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Lee, I., Kesner, R. Differential contribution of NMDA receptors in hippocampal subregions to spatial working memory. Nat Neurosci 5, 162–168 (2002). https://doi.org/10.1038/nn790

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