GoingToMeet

This meeting will include a discussion of the major excitatory (glutamate) and inhibitory (GABAA) ionotropic receptors in the brain. This will bring together experts from both fields (listed below in parentheses) to permit a discussion of how these receptor systems interact to control behaviour, learning/memory and disease. It is clear that the modulation of receptor function (Sigel, Wyllie, Czajkowski) alone does not explain the full repertoire of effects of neuronal plasticity. Receptor function is also influenced by auxiliary protein interactions and its location (Smart, Moss, Collingridge, Harvey). Indeed, receptor localization is highly plastic, being manipulated by neuronal activity (Collingridge, Smart, Malenka, Smith) and hormones (Harvey, Smith). These molecular changes occurring at the subcellular level are reflected in changes in cognition and behaviour (Mohler, Bannerman, Orser, Smith). Remarkably, individual receptor subtypes appear to play specific roles in behaviour and the clinical responses to therapeutic drugs (Mohler, Orser). Moreover, gross alterations in the balance of neuronal activity may lead to cognitive impairment (Bannerman, Mohler, Malenka) and disease states such as epilepsy (Walker).

The use of cell model systems have permitted a physiological and molecular characterization of neuronal excitotoxicity. Distinct NMDA receptor subtypes play opposing roles in the activation of distinct calcium signalling pathways (Hardingham), leading to changes in neuronal morphology (Connolly) and mitochondrial dysfunction (Nicholls).

Beyond the immediate consequences of altered neuronal morphology and physiology are the long-term changes in gene expression, following normal (Grant, Morris) and pathological (Zukin) activity. Insights into the significance of these changes are highlighted by the altered expression of either the receptors themselves (Smith), or of molecular chaperone (Morris) or scaffold (Grant) proteins.