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Long-term potentiation and contextual fear conditioning increase neuronal glutamate uptake

Nature Neuroscience volume 5, pages 155–161 (2002)Cite this article

Abstract

Induction and expression of long-term potentiation (LTP) in area CA1 of the hippocampus require the coordinated regulation of several cellular processes. We found that LTP in area CA1 was associated with an N-methyl-d-aspartate (NMDA) receptor–dependent increase in glutamate uptake. The increase in glutamate uptake was inhibited by either removal of Na+ or addition of d,l-threo-β-hydroxyaspartate. Dihydrokainate (DHK), a specific inhibitor of the glial glutamate transporter GLT-1, did not block the increase in glutamate uptake. LTP was also associated with a translocation of the EAAC1 glutamate transporter from the cytosol to the plasma membrane. Contextual fear conditioning increased the maximum rate (Vmax) of glutamate uptake and membrane expression of EAAC1 in area CA1. These results indicate that regulation of glutamate uptake may be important for maintaining the level of synaptic strength during long-term changes in synaptic efficacy.

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Figure 1: HFS increased glutamate uptake in area CA1 of hippocampus.
Figure 2: Changes in expression of glutamate transporters in a plasma membrane fraction from area CA1 30 min after induction of LTP.
Figure 3: HFS produced translocation of EAAC1 from the cytosol to the membrane.
Figure 4: Contextual fear conditioning increased glutamate uptake in area CA1 in vivo.
Figure 5: Contextual fear conditioning increased neuronal glutamate transporters in area CA1.

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Acknowledgements

We thank J.H. Byrne, D. Baxter and E. Antzoulatos for discussions and critical reviews. This work was supported by NIH grants MH48147 (to J.D.S.), NS28462 (to A.E.) and NS42156 (to A.E.).

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Authors and Affiliations

  1. Department of Biology and Biochemistry, University of Houston, Houston, 77204, Texas, USA

    Jonathan Levenson, Lorna S. Kategaya & Arnold Eskin

  2. Division of Neuroscience, Baylor College of Medicine, Houston, 77030, Texas, USA

    Edwin Weeber, Joel C. Selcher & J. David Sweatt

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  1. Jonathan Levenson
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Correspondence to Arnold Eskin.

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Levenson, J., Weeber, E., Selcher, J. et al. Long-term potentiation and contextual fear conditioning increase neuronal glutamate uptake. Nat Neurosci 5, 155–161 (2002). https://doi.org/10.1038/nn791

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