Ganglion cells in the retina are the output neurons which conduct the visual-evoked neural activity of the retina to the visually responsive areas of the brain. The ganglion cells, driven by complex patterns of excitation and inhibition from the presynaptic neurons, are the final integration sites for the processing of visual information in the retina. As such, they a vital role in vision. We can further our understanding of this role and also how the retina functions by determining the pathways, characteristics, and underlying mechanisms of the excitation and inhibition of the ganglion cells. This information will, in turn, will help us to understand how retinal pathologies and degenerations might manifest themselves. Experimentally, we seek to understand the mechanisms by which ganglion cells are excited, which other studies have shown is produced by glutamatergic synaptic inputs from bipolar cells. We will extend our own previous work in which we were able to record normal light-evoked ganglion cell activity under voltage-clamp conditions in the slice preparation. We want to learn how the overall time course of the light responses is generated. We would like to understand how the concurrent activation of two different classes of glutamate receptor is combined to produce the excitatory light response. Further we propose experiments to determine whether the identified on nonNMDA and NMDA glutamate receptor inputs are co-localized at the same synaptic site. In collaboration with Drs. Myers and Peterson, we hope to identify the glutamate subunits mediating the excitatory inputs to ganglion cells. Also, we will test whether there are use-dependent changes in the synaptic transmission to ganglion cells, similar to the long term potentiation seen at synapses in the brain. Finally, we will test whether there could be direct synaptic excitation between ganglion cells as found in catfish retina. If we find either or both long term potentiation or mutual excitation we will investigate the mechanisms of these interactions. The promise of this project is that we can combine the latest techniques in retinal neurobiology with state-of- the-art methodologies and findings from the molecular biology and pharmacology of glutamate receptors to determine in exquisite detail the mechanisms by which visual-evoked excitation is generated in the ganglion cells. These findings will likely serve as a prototype for the mechanisms underlying glutamatergic synaptic transmission in other parts of the nervous system.
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