Neale, Stuart Andrew; (2002) Metabotropic glutamate receptors and synaptic transmission in the cerebellar cortex. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The metabotropic glutamate (mGlu) receptors are a family G-protein-coupled receptors; the 8 members of which are divided into 3 groups. In the rat cerebellum, pre- and postsynaptic mGlu receptors exist at the parallel fibre-Purkinje cell synapse, and exogenously-applied agonists can depress glutamatergic synaptic transmission both at this synapse, and at others in the CNS. There is, however, relatively little evidence that the synaptically released agonist has these actions. Using an in vitro slice preparation and single cell electrophysiological recording techniques, the principle aim of the research described in this thesis has been to identify conditions under which these receptors might be activated by synaptically released agonist. Using agonists and antagonists of the mGlu receptors that act differentially on the 3 groups of mGlu receptors expressed in heterologous expression systems, it was found that activation of the group I and group III receptors caused a reversible reduction in the AMPA receptor-mediated EPSP amplitude, and appropriate antagonists inhibited these effects. Agonists of the group II receptors had no effect on transmission at this synapse. Brief tetanic stimulation of the parallel fibres was found to result in a depression of synaptic transmission that lasted for several seconds after the end of the tetanus, a phenomenon we have termed post-tetanic depression. Through the use of selective antagonists, this novel form of synaptic depression was found to be mediated by GABAB receptors and group I mGlu receptors. These receptors are probably located pre- and postsynaptically respectively. It is concluded that the group I and III mGlu receptors can depress excitatory synaptic transmission in the rat cerebellum. In addition, the results indicate that postsynaptic group I mGlu receptors have a previously undescribed role in short-term synaptic plasticity. These observations provide the first evidence that the group I mGlu receptors may be activated by synaptically released agonist to depress synaptic transmission.

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