A Specific Role for Group I mGluRs in Hippocampal LTP and Hippocampus-Dependent Spatial Learning

  1. Detlef Balschun1,2,5,
  2. Denise Manahan-Vaughan1,
  3. Thomas Wagner3,
  4. Thomas Behnisch2,4,
  5. Klaus G. Reymann2,4, and
  6. Wolfram Wetzel3
  1. 1Department of Neurophysiology, 2Project Group Neuropharmacology, 3Laboratory of Behavioral Pharmacology, Leibniz Institute for Neurobiology 39008, Magdeburg, Germany; 4Research Institute for Applied Neurosciences GmbH, 39120 Magdeburg, Germany

Abstract

Metabotropic glutamate receptors (mGluRs) have been implicated in long-term potentiation and in learning and memory formation. In this study, we tested the effects of group I mGluR inhibition on synaptic plasticity and learning of rats at different levels of organization (1) in the hippocampal slice preparation; (2) in freely moving animals implanted with chronic hippocampal electrodes; and (3) in different spatial learning paradigms. To allow a direct comparison of the effects obtained the same doses were used in all paradigms. Bath-application of the selective group I mGluR antagonist (S)4-carboxyphenylglycine (4-CPG) impaired a decremental long-term potentiation (LTP) induced by a weak tetanization paradigm, but failed to affect a robust LTP generated by strong tetanization. In contrast, 4-CPG impaired a robust LTP in freely moving animals if applied 30 min before tetanization. The same dose of 4-CPG only impeded spatial learning mildly in the eight-arm radial maze and had no effect on a simple configuration of the Y-maze spatial alternation task. In the more difficult configuration of this task, however, 4-CPG caused complete amnesia. The lack of state-dependent 4-CPG actions and the absence of any 4-CPG effects in the open-field test classify the obtained retention deficit as a selective impairment of memory storage. Our results indicate a specific role of group I mGluRs in certain types of synaptic plasticity and of spatial learning.

Footnotes

  • 5 Corresponding author.

    • Received August 6, 1998.
    • Accepted February 26, 1999.
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