Metabotropic glutamate receptors in the plasticity of excitatory responses in the hippocampus. Clinical impact.

Abstract

Excitatory connections in the hippocampal network have been shown to exhibit plasticity when subjected to specific modes of activation. These include short term and long term potentiation (STP and LTP, respectively) as well as long term depression (LTD). Ionotropic glutamate receptor (iGluR) activation, especially that mediated via NMDA receptors, is key in regulating many of these processes and is discussed in more detail in other chapters in this text. This chapter will demonstrate the participation of metabotropic glutamate receptors (mGluRs) in the plastic processes of the hippocampal circuit and will emphasize the possible clinical relevance of these processes. I will first provide a review of the receptor classification and the actions of the various mGluR subgroups. I will briefly summarize the work to date demonstrating the different ways in which each of these subgroups participates in synaptic plasticity. I will discuss ways in which mGluR-mediated activities may influence clinical conditions such as epilepsy. And finally, I will present the results of my studies on the role of these receptors in the production of epilep-tiform activities in the in vitro hippocampus, focusing on their unique capacity for autopotentiation, providing a potential mechanism for epileptogenesis.