Glutamate receptors and the electrophysiological properties of sympathetic preganglionic neurones
The main aim of this thesis was to examine the role of metabotropic glutamate receptors (mGluRs) in the control of the excitability of sympathetic preganglionic neurones (SPNs). A review of the literature concerning SPNs and glutamate receptors has been performed. Experiments were made using whole-cell patch-clamp recordings from neurone in slices of spinal cord. During recording neurones were perfused with either Lucifer yellow or biocytin and following recording the slices were processed and the morphology of the neurones examined. SPNs were identified by their characteristic electrophysiological and morphological properties. The pharmacology of mGluR agonist-induced changes in the excitability of SPNs was examined. Almost all SPNs demonstrated a depolarisation with a pharmacological profile suggesting that it was mediated by a group I mGluR. A minority of SPNs also demonstrated hyperpolarising responses to agonists with activity at group II mGluRs, suggesting that activation of group II mGluRs may have inhibitory effects on some SPNs. Activation of mGluRs modulated the frequency of ongoing membrane potential oscillations and induced membrane potential oscillations in a subpopulation of previously silent SPNs. Responses involving induction of oscillations or increases in the frequency of spontaneous oscillations had agoinst profiles suggesting involvement of a group I mGluR, and responses involving decreases in the frequency of oscillations had agonists profiles suggesting that they were mediated by a group II mGluR. This study has demonstrated excitatory and inhibitory effects mediated by activation of different mGluRs on SPNs and has investigated some of the underlying mechanisms. Activation of mGluRs was also shown to modulate glutamatergic synaptic inputs to SPNs. Synaptically evoked responses mediated by mGluRs remain to be demonstrated.