Retinal dopamine appears involved in light adaptation in all vertebrates, including human. Dopamine depletion in goldfish retina causes a chronic 100-fold increase in light sensitivity. When the retina is reinnervated with a sparse plexus of dopamine processes, synaptic contact is reestablished with horizontal cells but not with ON bipolar cells. It is hypothesized that synaptic contact is necessary for dopamine control of bipolar cells that are responsible for a normal transition from light-to dark-adaptation. It is predicted that horizontal cell responses to dopamine are independent of direct dopamine innervation, whereas bipolar cells depend upon direct dopamine input. These predictions will be tested in electrophysiological and immunocytochemical studies in control, dopamine-depleted (depleted by intraocular injection of 6-hydroxydopamine) and partially reinnervated retinas.
Specific aim 1 is to determine electrophysiological properties (voltage- and ligand-gated) of bipolar cells (using whole-dell recording) and horizontal cells (by intracellular recording) in the retinal slice. Initial focus will be on K+ currents, effects of ascorbate, dopamine D1 ligands and GABA.
Specific aim 2 proposes to use immunocytochemistry to determine the content and distribution of transmitter- and channel-specific markers by light and electron microscopy. Initial focus will be on K+ channels, glutamate-, dopamine D1- and GABAc-receptors. In addition, it is proposed to use antibodies against agmatine, a selective permeant of cation channels gated by AMPA/NMDA receptors, to determine the relative activity of horizontal cells and OFF bipolar cells.
Specific aim 3 is to test the hypothesis that color opponency of bipolar cells is due to direct input from photoreceptors, rather than feedback from horizontal cells, by determining the chromatically-induced intracellular responses of bipolar and horizontal cells in the retinal slice. This project will provide data regarding: (1) the cellular basis of the acute, chronic and recovery phase of dopamine depletion on luminosity coding, (2) elucidation of a dual mechanism for the control of retinal processes by dopamine, i.e., volume and wiring transmission, and (3) the relative contribution of horizontal cells and bipolar cells to luminosity and color coding.
Showing the most recent 10 out of 74 publications
