Modulation of synaptic communication between neurons is a fundamental mechanism by which the nervous system responds to changing levels of stimuli, reflects previous experience and shapes functional connections during development. The broad goal of the research proposed here is to gain an understanding of the mechanisms of electrical synaptic plasticity at a molecular level using synaptic modulation in the outer plexiform layer of the retina as an experimental system. The proposed experiments focus on three specific aims; (1) extending successful studies of synaptic modulation at the single channel level to include modulation by nitric oxide, cGMP and pH, in addition to dopamine, (2) accelerating efforts in progress directed at cloning cDNAs for teleost retinal gap junction channel genes, and (3) expanding the scope of research to examine the regulation of assembly and maintenance of electrical synapses by dopamine, cell calcium and cell-cell adhesion. Successful completion of these experiments will contribute in a fundamental way to our understanding of the modulation of electrical synaptic transmission in the nervous system. This basic knowledge should be useful in understanding the pathophysiology of epilepsy, Parkinsonism, schizophrenia and senescence, where these processes are apparently deranged.
Lu, C; Zhang, D Q; McMahon, D G (1999) Electrical coupling of retinal horizontal cells mediated by distinct voltage-independent junctions. Vis Neurosci 16:811-8 |
Wagner, T L; Beyer, E C; McMahon, D G (1998) Cloning and functional expression of a novel gap junction channel from the retina of Danio aquipinnatus. Vis Neurosci 15:1137-44 |