Clinicn Investigator, Full Prf Neurology, Mass General Research Institute

Joseph P. and Rose F. Kennedy Professor of Child Neurology and Mental Retardation Harvard Medical School

Neurologist Neurology, Massachusetts General Hospital

Pediatric Neurology Residency University of California San Diego School of Medicine 1989

Pediatric Residency University of California San Diego School of Medicine 1986

Dana Fellowship, Department of Neurology and Neurosciences Stanford University, Palo Alto, California 1991

Neurology Residency University of Colorado Health Sciences Center, Denver 1987

MD UC San Diego School of Medicine 1984

action potentials; anticonvulsants; brain injury; bumetanide; chloride concentrations; chlorides; cortical seizures; epilepsy; epileptogenesis; gaba; gaba signaling; hippocampus; neuronal ion transport; seizures; sodium potassium chloride symporter inhibitors; sodium-potassium-chloride symporters

Our long-term research goal is the development of new approaches to the treatment of epilepsy based on a clearer understanding of the necessary steps in seizure initiation and propagation.

The two major themes in the lab are neuronal ion transport and the spread of activity in neural networks. Neuronal ion transport underlies signaling at all fast synapses. The importance of neuronal ion transport was underscored by our recent discovery that reversed ion transport in the immature brain was blocking the effects of the anticonvulsants most commonly used to treat neonatal seizures, and that a safe and well-characterized diuretic could ameliorate this condition.

Our work on the spread of excitation in neural networks combines fluorescent imaging of network activity with computerized analysis and modeling to understand how normal and abnormal signaling progresses through neural networks. We have found evidence for reentrant or circular patterns of neural activity that resemble cardiac fibrillation and precede seizures. We are currently testing whether this reentrant activation of neural circuits is the earliest stage of a seizure, and the stage at which intervention is most effective. We are also testing whether long-term reductions in the strength of synaptic connections between neurons in epileptic networks can reduce the probability of seizures.