Christopher James McBain, Ph.D.

Hippocampal Interneurons and Their Role in the Control of Network Excitability

Cortical and hippocampal local circuit GABAergic inhibitory interneurons are “tailor-made” to control Na+- and Ca2+-dependent action potential generation, to regulate synaptic transmission and plasticity, and to pace large-scale synchronous oscillatory activity. The axons of this diverse cell population make local, short-range projections (although some subpopulations project their axons over considerable distances) and release the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) onto a variety of targets. A mounting appreciation of the roles played by interneurons in several mental health conditions such as epilepsy, stroke, Alzheimer's disease and schizophrenia have placed this important cell type center stage in cortical circuit research. Our main objective is to understand how both ionic and synaptic mechanisms regulate the activity of local circuit GABAergic interneurons and principal neurons at the level of small well-defined networks. To this end, we use a variety of electrophysiological, immunohistochemical, molecular, and genetic approaches in both wild-type and transgenic animals. Over the past five years, we have continued our study of the differential mechanisms of glutamatergic and GABAergic synaptic transmission and plasticity within the hippocampal formation and the modulation of voltage- and ligand-gated channels expressed in inhibitory neurons. We also incorporate genetic approaches to unravel the embryogenesis and development of hippocampal interneurons and the circuits in which they are embedded.

Dr. Chris McBain received his BSc from the University of Aberdeen, Scotland and a Ph.D. from the University of Cambridge, England, where he worked with Dr. Ray Hill studying spontaneously arising epileptiform activity in the rat hippocampus. During a postdoctoral fellowship with Dr. Raymond Dingledine at the University of North Carolina at Chapel Hill, he studied glutamate receptor function, regulation of the extracellular volume fraction, and hippocampal synaptic transmission with particular relevance to the epilepsies. After a brief period in the laboratory of Dr. Julie Kauer at Duke University, Dr. McBain joined NICHD as an Investigator within the Laboratory of Cellular and Molecular Neurophysiology. He is currently Scientific Director (Acting) and a Senior Investigator within the NICHD DIR. His laboratory is studying the role of inhibitory interneurons in the development of hippocampal and cortical circuits as well as mechanisms of cortical and hippocampal synaptic transmission and the role of voltage-gated channels in the regulation of excitability within hippocampal circuits in health and disease states.