University College London

Prof. Dr. Trevor Smart
Torrington Place 2-16
WC1E 7HN London
United Kingdom

The Research Department of Neuroscience, Physiology and Pharmacology is part of the School of Life and Biomedical Sciences at UCL. It is organised into three major research groups: Cellular and Molecular Neuroscience, Systems Neuroscience and Intercellular Signalling. At the molecular level this encompasses studies on receptors, intracellular signalling, ion channels and transporters. At the cellular level, it covers most aspects of signalling within and between neurons, and also glia. At the systems level, it includes the function of neuronal networks and their relationships to higher-order cognitive processing.

Using multidisciplinary integrated approaches, based on electrophysiology, cell and molecular biology, imaging and neurogenetics, the group led by Professor Trevor Smart specializes in elucidating the molecular and network properties of GABAA and glycine receptors. In particular, a large component of our work focuses on structure-function analyses of GABAA and glycine receptors, deducing how these receptors are activated by transmitters and also modulated by endogenous ligands in the brain.

For network, whole-cell synaptic and single channel studies, we use native neurones coupled with optical and genetic adaptations to modify the response profile of GABAA receptors. To gain proof-of-principle for our manipulations of GABAA receptor structure-function, we employ numerous DNA or RNA tranfection methods. In addition, we are also using imaging/optical techniques, with various fluorophores and photo-activated caged compounds, to enable the tracking in live cells of receptor subunits in real time into and out of inhibitory synapses.

At the synaptic and network levels, similar approaches are used to study the physiological control of inhibitory transmission and synaptic plasticity by retrograde and autocrine messengers. This also includes how other endogenous regulators in the nervous system (e.g., phosphorylation and neurosteroids) can modulate the function of specific GABAA receptors at specific inhibitory synapses to affect network behaviour.

Overall, our major objective is to provide a complete molecular description of the therapeutically important GABAA receptor classes that will enable a deeper understanding of their role in neuronal networks in both healthy and diseased states. Next partner >