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David Sprinzen, Michael L Risner, Douglas McMahon; The differential role of dopamine on the response characteristics of retinal ganglion cell subtypes.. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2381.
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© ARVO (1962-2015); The Authors (2016-present)
We investigated the effect of dopamine on spatial and temporal response dynamics of retinal ganglion cells (RGCs) by comparing wild type and retinal tyrosine hydroxylase knockout mice (rThKO). Previous studies have shown significant effects of dopamine in the retina in light adaption, however it is unclear how dopamine may affect the different channels of light encoding. We used a multi-electrode array (MEA) and recorded from RGCs while showing various patterns of light stimulation to both dark adapted and light adapted retinas.
Mouse retinas were dissected in dim red light, placed ganglion cell side down on perforated MEAs,and perfused with oxygenated Ames’. Stimulation protocols were delivered through a monochrome microLED monitor. In a marching square protocol a 120 x 120 µm square (32 cd/m2) was indexed through a 12 x 16 grid covering the MEA and the induced spike frequency was correlated to the stimulus position to create a receptive field map. Cells were defined as ON, OFF, or ON/OFF and sustained or transient based on the response at the receptive field center. A white noise protocol consisted of a binary randomly flickering checkerboard updated at 75 Hz. The receptive field and response latency were defined through retro-correlating the spike triggered average stimulus for each cell. Directionally selectivity was assessed with a full-field moving bar in eight directions, from 0 to 315 degrees in 45-degree intervals.
Dopamine knock out in the retina caused divergent functional changes in different retinal ganglion cell types. In OFF-center cells, exhibited a significant decrease in the response duration under dark-adapted conditions but an increase in the response time under light-adapted conditions. ON-center transient cells and ON-OFF directionally selective cells, showed a significant decreases in the receptive field size in the dark adapted state but a slight increase in the light adapted state, representing an overall blunting of the effect of light in manipulating the adapted state of the retina.
The heterogeneous effects of dopamine knock out on RGCs may represent divergent roles of these information channels in relation to light adaption. In the future, we plan on using D1 and D2 receptor agonists to assess the relative contribution of signaling pathways to the functional changes we found.
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