Get access

Requirement of appropriate glutamate concentrations in the synaptic cleft for hippocampal LTP induction

Authors

  • Hiroyuki Katagiri,

    1. Department of Neurophysiology, Faculty of Medicine, University of Tokyo, Tokyo 113–0033
    Search for more papers by this author
    • *

      Present address: Laboratory for Neuronal Circuit Development, Brain Science Institute, RIKEN, Saitama 351–0198 Japan

  • Kohichi Tanaka,

    1. Department of Molecular Neuroscience, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113–8519
    Search for more papers by this author
  • Toshiya Manabe

    1. Department of Neurophysiology, Faculty of Medicine, University of Tokyo, Tokyo 113–0033
    2. Division of Neuronal Network, Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, Tokyo 108–8639
    3. Department of Physiology, Kobe University School of Medicine, Kobe 650–0017 Japan
    Search for more papers by this author

: Dr Toshiya Manabe, 4Dept. Physiology, as above.
E-mail: tmanabe-tky@umin.ac.jp

Abstract

Although glutamate transporters maintain low extracellular levels of the excitatory neurotransmitter glutamate in the nervous system, little is known about their roles in synaptic plasticity. Here, using knockout mice lacking GLT-1, that is the most abundant glial subtype of glutamate transporters, we showed that long-term potentiation (LTP) induced by tetanic stimulation in mutant mice was impaired in the hippocampal CA1 region. When tetanic stimulation was applied in the presence of low concentrations of an N-methyl-d-aspartate (NMDA) receptor antagonist, the impairment was overcome. Consistent with these results, the increased glutamate in the synaptic cleft of mutant mice preferentially activated NMDA receptors. Furthermore, analyses of mutant mice revealed that the magnitude of NMDA receptor-dependent transient synaptic potentiation during low-frequency stimulation depended on the concentration of glutamate in the synaptic cleft. These findings suggest that GLT-1 plays critical roles in LTP induction, as well as in short-term potentiation, through regulation of extracellular levels of glutamate, which enables appropriate NMDA receptor activation.

Ancillary