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T. J. Viney, B. Roska; Cell Type Specific Interactions Between Excitation and Inhibition in Genetically-Identified Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1414.
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To find cell type specific rules in the dynamic interaction of excitation and inhibition in genetically-identified ganglion cell subtypes in the mouse retina.
A conditional reporter system was used to generate mice that express GFP in subsets of retinal ganglion cells. Two-photon confocal laser imaging was used to detect the GFP-positive ganglion cells in light-adapted wholemount retinas. Z-stacks were used to select a cell type. Whole-cell voltage-clamp recordings were used to characterize the excitatory and inhibitory inputs during light stimulation. Stimuli were mapped to the dendritic field center and flashing or moving discs were used to explore how the ON and OFF inputs shaped the spiking output. Several genetically-identified cells were recorded from and filled with Neurobiotin in each retina. Retinas were fixed, and morphological analysis was carried out using markers for cholinergic strata (ChAT) and GFP. The two-photon images were used to map each recorded cell with their corresponding confocal image to correlate physiology with morphology.
From the population of genetically-identified cells, six morphologically distinct ganglion cell types were found, which stratified in different depth in the inner plexiform layer. Five out of six cell classes were both morphologically and physiologically similar to identified rabbit ganglion cells. In each cell type excitation, inhibition and spiking had a highly repeatable time course for different test stimuli, including moving or flashed objects and more natural movies. Statistical analysis of the relative timing of excitation, inhibition and spiking revealed cell type specific rules in the dynamic interaction of excitation and inhibition.
Two-photon imaging of genetically-labeled retinas made it possible to repeatedly target six genetically and morphologically identified ganglion cell types for physiological recordings. This enabled us to compare the dynamic interactions between excitation and inhibition in well defined classes of ganglion cells. Our results suggest that in each ganglion cell type the timing of inhibition and excitation is very precise and the relative timing of inhibition and excitation has a major influence on the spiking output during visual stimulation.
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