A specific role for group I mGluRs in hippocampal LTP and hippocampus-dependent spatial learning

• Published in: Learning & memory (Cold Spring Harbor, N.Y.) N.Y.), 1999-03, Vol.6 (2), p.138-152
• Main Authors: Balschun, D, Manahan-Vaughan, D, Wagner, T, Behnisch, T, Reymann, K G, Wetzel, W
• Format: Article
• Language: English
• Subjects: 4-Carboxyphenylglycine; Animals; Benzoates - pharmacology; Electrophysiology; Evoked Potentials, Somatosensory - drug effects; Evoked Potentials, Somatosensory - physiology; Excitatory Amino Acid Antagonists - pharmacology; Glycine - analogs & derivatives; Glycine - pharmacology; hippocampal slice; Hippocampus - physiology; Long-Term Potentiation - physiology; Male; Maze Learning - physiology; Neuronal Plasticity - physiology; Rats; Rats, Wistar; Receptors, Metabotropic Glutamate - physiology; Research Paper
• ISSN: 1072-0502; 1549-5485
• DOI: 10.1101/lm.6.2.138

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.