Physiology and Neuroscience of Vision
My primary research interest is focused on the vertebrate retina, a unique, well organized neural network that carries out sophisticated computations on the visual image. Four general areas occupy most of my experimental efforts. The first relates to the mechanisms of synaptic transmission in the retina, with special emphasis on glutamate receptors. More recently this project has morphed into how D-serine serves to regulate NMDA receptor sensitivity among amacrine and ganglion cells. Second, I have a long-standing interest in the relationships between structure and function of single cells and this has led to computational approaches to these problems, including the use of computer simulations to replicate physiological observations. In recent years my colleagues and I have developed models of multichannel impulse encoding, the role of T-type calcium channels in dendritic integration and impulse generation and the role of NMDA and AMPA receptors in synaptic transmission. A third area involves the use of fluorescent dyes to study functional properties of cells, including the use of activity-dependent dyes, combined with confocal microscopy and dyes to study intracellular calcium, pH, and chloride activity. A fourth research area relates to the function of glial cells in the retina, principally the Müller cells and how they generate calcium waves and respond to externally applied NAD. We have recently acquired a two-photon microscope and have initiated new experiments related to events such as back-propagated action potentials in retinal ganglion cells.
Methods used in my laboratory include intracellular, whole-cell and patch-electrode electrophysiological techniques applied to the intact retina, retinal slices, and dissociated cells. Optical techniques include fluorescence microscopy, confocal microscopy, 3D image reconstruction techniques. The two-photon confocal microscope has now been added to our experimental repertoire and will be focused on the physiological properties of ganglion cell dendrites. We also use high-speed computers with specialized software (Neuron and MCell) to carry out studies of single cell structure and function relationships, including diffusion of neurotransmitter and receptor kinetics.
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