The Role of Dopamine on Inhibition in the Mouse Retina

Abstract

One truly remarkable feature of the retina is its ability to adapt to a wide range of lightintensities over the span of minutes. The retina is a sensory organ that must be sensitive in low light conditions while also being able to maintain a high degree of resolution of its outputs during large amounts of input. While several mechanisms likely mediate this phenomenon, one source of regulation is in the neuromodulator dopamine. Dopamine is a known neuromodulator in the central nervous system and binds to one of five dopamine receptors, three of which are located in the mouse retina. Dopamine is produced by a subset of amacrine cells known as the dopaminergic amacrine cells. The release of dopamine in the retina is thought to be a gradual secretion throughout the day, dependent on increasing light levels. The subsequent binding of dopamine to one of its receptors mediates differential modulatory effects depending on the receptor subtype and the cell type targeted. Much of the work involved in measuring the effects of dopamine in the retina has involved perfusing dopamine or applying dopamine like agonists and antagonists that are specific to D1, D2, or D4 receptors. However, these receptors each reside on multiple cell types and even subtypes. The role of this work is to determine how dopamine modulates neural signaling at specific connections by utilizing a technique known as optogenetics to isolate inhibitory circuitry in the retina and determine if dopamine is modulating circuitry directly. Electrophysiological measurements of single neurons and light-evoked potentials across the retina are used to determine the direction and scale of such modulation. Understanding the role of dopamine in modulating neural signals in the retina is important for understanding how vision is processed throughout changing light conditions. Additionally, as the most peripheral part of the central nervous system, the retina gives important insight into the modulatory capacities of dopamine in the rest of the brain. This may be particularly important in the study of some diseases such as Parkinson’s and diabetes, demonstrating early homeostatic shifts in dopamine mediated neurocircuitry.