LABORATORY OF CELLULAR AND SYNAPTIC NEUROPHYSIOLOGY
 
   
Chris J. McBain, Ph.D. Chief  
   

The Laboratory of Cellular and Synaptic Neurophysiology uses the techniques of neurophysiology, molecular biology, and cell biology to study signalling mechanisms related to the development, physiology, and pathophysiology of the mammalian central nervous system. Specifically, we study receptors, ion channels, and signalling mechanisms in preparations that range from isolated cells to highly ordered neural networks in physiological and pathophysiological conditions in both wild-type and transgenic animals. Problems under analysis concern mechanisms of short- and long-term plasticity of synaptic transmission, neurotrophin regulation of excitability and development, differential targeting of synaptic receptors, neuron-glial signalling, pathophysiological processes in clinically relevant neuronal migration disorders, ion channel regulation of development and excitability, and drug action at a variety of voltage- and ligand-gated receptors.

During the last year, Chris McBain conducted an extensive characterization of Ca2+-permeable, GluR2-lacking AMPA-, and NMDA-receptors at hippocampal inhibitory interneuron synapses. His group elucidated the time course of electrotonically overlapping but kinetically distinct synaptic conductances on inhibitory interneuron dendrites and the roles of voltage-gated conductances in the generation of muscarinic receptor– and kainate receptor–induced hippocampal gamma oscillatory activity. Doug Fields elucidated the role of adenosine as a neuron-glial transmitter that promotes myelination in the central nervous system in response to action potential activity. He also studied the role of electrical activity in regulating late-phase long-lasting synaptic plasticity. Bai Lu worked on activity- and tyrosine kinase–dependent facilitation of trkB receptor internalization in hippocampal neurons and discovered the presence of single nucleotide polymorphisms in the BDNF gene and the role played by the polymorphisms in BDNF secretion and hippocampal function, with particular reference to memory formation. James Russell investigated the kinetics of Ca2+ release from Ca2+-signalling microdomains and the pattern of type 2 IP3Rs expressed by astrocytes in situ.

Both Drs. Fields and Lu gained tenure. Dr. McBain was elected to the editorial board of the Journal of Physiology and Journal of Neuroscience. Finally, the laboratory made considerable effort to recruit two independent researchers to the NICHD tenure track: in fall 2002, Drs. Dax Hoffman and Mark Stopfer joined the LCSN. Dax Hoffman combines patch clamp recording in brain slices of hippocampus with molecular biology techniques to investigate the electrophysiological properties and molecular nature of the voltage-gated channels expressed in CA1 dendrites. Mark Stopfer combines imaging, patch clamp physiology, and behavioral analysis to investigate synaptic and network mechanisms underlying sensory processing and memory formation, including coding mechanisms involving the oscillatory interactions of ensembles of interneurons in the insect antennal lobe.