A fundamental topic in neuroscience is how neurons adapt to a dynamic environment. Neural adaptation is the change in neural response to a chronic stimulus. Neural adaptation has been observed across several sensory systems, including somatosensory, auditory, and visual systems. In the visual system, adaptation initially occurs in the retina. The retina offers a unique format to investigate neural adaptation because the entire network of neurons is constrained to an approximately 250uM thick sheet of neural tissue. The network of retinal neurons is capable of seamless function over an enormous range of luminance levels. These retinal neurons continue to operate, extending vision, by amplifying weak signals or reducing strong signals to prevent saturation. The ability of these retinal mechanisms to adjust to the dynamic range of mean luminance levels is called light adaptation. Light adaptation involves at least two separate mechanisms: photoreceptor adaptation and network adaptation, which involves the synapses between post-photoreceptor neurons and retinal ganglion cells (RGCs). In the retina, dopamine is thought to be a chemical messenger for light adaptation. To investigate the impact of dopamine on light-adapted vision our laboratory has recently created and characterized a genetic mouse model in which retinal dopamine is knocked out. In a recent publication our laboratory has shown that light-adapted vision is severely impaired in this mouse model. Thus, this genetic model provides a unique format to rebuild the retinal dopamine circuitry through pharmacological manipulation to investigate how dopamine mediates network light adaptation in the retina. The overall goal of this project is to genetically and pharmacologically dissect the distinct dopamine retinal pathways involved in network light adaptation in physiologically defined RGCs. I have performed initial experiments examining how dopamine influences network light adaptation in physiologically defined RGCs by using single-cell loose patch recording. Results from these experiments provide evidence that dopamine is required for network light adaptation in two RCG subtypes.
The first aim of this project is to the further characterize the effect of dopamine on these RGC subtypes by examining if distinct dopamine receptors regulate network light adaptation in these RGCs. Using these initial experiments as the foundation I plan to migrate experiments from single- to multi-cell recording where a greater understanding of dopaminergic influence on network light adaptation will be gained in other RGC subtypes. Using multielectrode array recording technique, I seek to examine the interaction between the prevailing light level and dopamine on receptive field organization and network light adaptation in physiologically defined RGCs. Successful completion of these studies will provide insight into the physiological mechanisms involved in retinal network light adaptation, and the underlying retinal circuitry involved in contrast sensitivity and visual acuity.

Public Health Relevance

Dopamine is a key neurotransmitter involved in network light adaptation in the retina. The overall goal of this project is to examine the impact of dopamine and light history on retinal circuitry. This research plan will provide insight into the inherent design of the retina and will contribute towards strategies to restore vision for people who were born without the ability of sight or have lost this ability due to a condition.

National Institute of Health (NIH)
National Eye Institute (NEI)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1)
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Agarwal, Neeraj
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Vanderbilt University Medical Center
Schools of Arts and Sciences
United States
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