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UCL Division of Biosciences

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Prof Trevor Smart

Prof Trevor Smart

Schild Professor of Pharmacology

Neuro, Physiology & Pharmacology

Div of Biosciences

Joined UCL
1st Apr 2002

Research summary

Controlling the innate excitability of neurons is vital for a healthy nervous system. There are various ways of achieving this aim, but by far the most important involves the inhibitory transmitter, GABA. Fast synaptic inhibition is achieved by rapid activation of GABA-A receptors whilst longer term modulatory effects on excitability are accomplished by GABA-B receptor activation. It is increasingly clear that there are many different isoforms of GABA-A receptors and these appear, in particular examples, to be targeted to discrete areas of the brain, and within single neurones, to discrete inhibitory synapses. Given the critical role(s) these receptors play in neuronal function, they form a logical target for therapeutic agents to ameliorate uncontrolled neuronal excitability, in addition to being involved in numerous neurological disorders, such as epilepsy and anxiety. Our research in neuroscience at UCL is supported by long-term programme grant funding from the Medical Research Council and the Wellcome Trust. We use multidisciplinary integrated approaches, based on electrophysiology, cell and molecular biology, imaging and neurogenetics, to elucidate the molecular and network properties of GABA receptors. These techniques, for network, whole-cell synaptic and single channel studies, are used in native neurones coupled with optical and genetic adaptations to modify the response profile of GABA-A receptors. To gain proof-of-principle for our manipulations of GABA-A receptor structure-function, we employ numerous DNA or RNA tranfection methods (allowing receptor expression in cells following viral infection, direct microinjection and lipofection). In addition, we are also using imaging/optical techniques, with various fluorophores and photoactivated 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 GABA-A receptors at specific inhibitory synapses to affect network behaviour. Overall, our major objective is to provide a complete molecular description of the therapeutically important GABA receptor classes that will enable a deeper understanding of their role in neuronal networks in both healthy and diseased states.

Teaching summary

Pharmacology lectures anbd tutorials

Medical tutorials

Education

University of London
PhD, Pharmacology | 1983
School of Pharmacy, University of London
B.Pharm, Pharmacology | 1977
Publications