TARP regulation of neuronal and glial calcium-permeable AMPARs in health and disease . (360G-Wellcome-086185_Z_08_Z)

The proposed programme aims to elucidate the roles played by TARPs in regulating CP-AMPARs during cell (neuron and glial) signalling and in certain important neurological disorders. We have four specific goals: (1) to determine the contribution of TARPs to a form of synaptic plasticity involving dynamic regulation of CP-AMPARs [functional studies patch-clamp techniques applied to cerebellar stellate cells in slices] (2) to elucidate fundamental mechanisms by which TARPs interact with , and control, functional properties of native and recombinant CP-AMPARs [patch-clamp recording from recombinant and native AMPARs, combined with calcium measurements and molecular biology] (3) to assess the role of TARPs in subcellular targeting and mobility of CP-AMPARs [immunocytochemistry and quantum dot-based tracking] (4) to investigate the role of TARPs in specific neurological conditions (affecting neurons and glia) where changes in the regulation of CP-AMPARs are implicated in di sease aetiology [patch-clamp methods, calcium imaging, immunocytochemistry and molecular biology in mouse models and glial-derived tumor cells]