Expertise and current research performed: The Institute of Neurology is a specialist postgraduate medical Institute of University College London. The Institute of Neurology is the premier research centre for the clinical neurosciences in the United Kingdom. It received the highest ranking (6*) in the latest Research Assessment Exercise, and has an international reputation in several areas, in particular neuroimaging, neurogenetics, movement disorders, molecular neuropathology and epilepsy research. The Institute is closely associated in its work with the National Hospital for Neurology & Neurosurgery, University College London Hospitals' NHS Trust, and in combination they form a national and international centre at Queen Square for teaching, training and research in neurology and allied clinical and basic neurosciences. The Department of Clinical and Experimental Epilepsy has a number of national and international collaborations, with especial emphasis in human neuroimaging, combined EEG and fMRI, and neurogenetics. The Experimental Epilepsy Group, within the Department of Clinical and Experimental Epilepsy, addresses the mechanisms underlying seizure initiation, propagation and termination, the mechanisms underlying susceptibility to seizures, and the cellular consequences of seizures. These areas are being explored with a combination of neurogenetics (small families, sporadic cases and common genetic variation), cellular electrophysiology, calcium imaging, and in vivo methods. Current projects are examining the consequences of mutations of Ca2+, K+ and other ion channels in patients with epilepsy and movement disorders. The group has a long-standing interest in understanding the mechanisms underlying the excitability of cells and circuits within areas of the brain and discovered a novel role for tonic inhibition in interneurons. A further research project explores the possibility of developing novel treatments for focal epilepsy based on viral vectors.

Facilities/Equipment: The department of clinical and experimental epilepsy has the following facilities available for this project: in vitro patch clamp facilities for brain slices; rodent video-EEG telemetry unit; fully equipped animal facility; genetics laboratory; histology laboratory including confocal microscopy; cell culture facilities.

Personnel involved in the project

Principal investigator: Matthew Walker (M). BA in physiology, Medical degree, PhD in medicine. Senior Lecturer in Neurology and Consultant Neurologist. Working in epilepsy research since 1993. PhD thesis (1997) on an experimental and clinical approach to the treatment of status epilepticus. 2000-2004, Advanced Wellcome Fellowship supervised by Professor Kullmann investigating GABAergic inhibition in the hippocampus. My present research interests include: status epilepticus, novel treatments of focal epilepsy, changes in synaptic physiology during epileptogenesis and GABAergic inhibition.

Dimitri Kullmann (M). Professor. MA DPhil FRCP FMedSci (Medicine/neuroscience). Professor of Neurology. Working in neuroscience since 1979. Consultant clinical neurologist since 1997. Research interests are: synaptic transmission (quantal analysis, discovery of ‘silent synapses’, spillover of neurotransmitter, tonic inhibition, LTP in interneurons, presynaptic Ca2+ imaging with multiphoton microscopy); ion channelopathies (episodic ataxia types 1 and 2; Ca2+ channel mutations linked to human epilepsy); epilepsy mechanisms (plasticity of synaptic and extrasynaptic signalling in experimental epilepsy); neurocritical care. Stephanie Schorge (F). PhD in Neuroscience. Research Fellow. Previously postdoctoral researcher with D. Lipscombe (Yale University), D. Colquhoun (University College London). Working in the field since 1992. Research interests are: splicing of ion channel genes, assembly and stoichiometry of ion channels, role of sodium channel genetic variability in epilepsy and drug sensitivity, biophysics. Simon Maltas (M). Technician. BSc in pharmacology. Research interests: molecular biology of paroxysmal neurological diseases

Two postdoctoral assistants will be required for the length of the project

Recent relevant publications/patents

1.        Scimemi A, Semyanov A, Sperk G, Kullmann DM, Walker MC. (2005) Multiple and plastic receptors mediate tonic GABAA receptor currents in the hippocampus. J Neurosci 25(43):10016-24.

2.        Imbrici P, Jaffe SL, Eunson LH, Davies NP, Herd C, Robertson R, Kullmann DM, Hanna MG. (2004) Dysfunction of the brain calcium channel CaV2.1 in absence epilepsy and episodic ataxia. Brain 127(12):2682-92

3.        Chandler K, Princivalle AP, Fabian-Fine R, Bowery NG, Kullmann DM, Walker MC. (2003) Plasticity of GABAB receptor-mediated heterosynaptic interactions at mossy fibers following status epilepticus. J Neurosci 23(36),11382-91

4.        Semyanov A, Walker MC, Kullmann DM (2003) GABA uptake regulates cortical excitability via cell type–specific tonic inhibition. Nature Neuroscience 6(5),484-90

5.        Ruiz A, Fabian-Fine R, Scott, Walker MC, Rusakov DA, Kullmann DM. (2003) GABAA receptors at hippocampal mossy fibers. Neuron. 39(6), 961-73.