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Changes in Inhibitory Retinal Circuits Following Partial Cone Loss

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Posterboard#: B0016

Abstract Number: 554 - B0016

AuthorBlock: Joo Yeun Lee1, Rachel Care1,2, Felice Dunn1
1Department of Ophthalmology, University of California San Francisco, San Francisco, California, United States; 2Graduate Program in Neuroscience, University of California San Francisco, San Francisco, California, United States;

DisclosureBlock: Joo Yeun Lee, None; Rachel Care, None; Felice Dunn, None;

Purpose
In human retina, visual function can be maintained despite partial loss of cone input. However, it is unclear how the visual system achieves functional resilience following cone loss. Here, we seek to understand the mechanisms that could contribute to circuit plasticity in mature retina.

Methods
To ablate cone photoreceptors in mature mouse retina, diphtheria toxin (DT) was injected intramuscularly at P30 mice expressing the simian diphtheria toxin receptor (DTR) under S-opsin promoter. Cone death was completed within 3 days and no subsequent cone loss was observed up to two months after DT injection. To investigate functional properties of retina with input loss, whole-cell current- and voltage-clamp recordings were made to measure voltages, excitatory, and inhibitory currents from alpha ON sustained ganglion cells (AON-S). We measured spatio-temporal receptive fields by presenting a random bar stimulus that draws intensity values from a Gaussian distribution at each time point and at each bar location. A linear-nonlinear model was used to interpret cell’s responses to the white noise stimulus generating receptive field maps. To reveal structural changes associated with functional properties, we biolistically delivered a plasmid encoding fluorescently tagged PSD-95 to quantify excitatory postsynaptic puncta.

Results
Control AON-S ganglion cells exhibit narrow depolarizing centers and wider hyperpolarizing surrounds. In DTR retina, the receptive fields, as measured by voltage output, have a narrower center and wider surround than in control retina. To identify the components that contribute to such changes, we measured excitatory and inhibitory input currents that contribute to the output voltage response. In DTR retina, the receptive field center, as measured in excitatory and inhibitory currents, decreased in center width. Furthermore, the increased surround width in DTR retina was explained by an expansion of the inhibitory surround. These results indicate a potential contribution of amacrine cells to the increase in surround width.

Conclusions
The mature retina is capable of modifying its circuitry upon input loss as evidenced by the expansion of the receptive field surround in DTR retina. These data guide us to examine structural and functional connectivity between amacrine cells and AON-S ganglion cells. Future studies will explore inhibitory partners with AON-S ganglion cells that shape their receptive fields.

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