Dopamine and motion perception: Unveiling retinal connections in Parkinson's disease

Abstract

Aims/Purpose: Parkinson's disease (PD) is characterized by degeneration of dopaminergic neurons, which occurs not only in the pars compacta of the sustantia nigra of the midbrain, but also in the retina, where dopaminergic amacrine cells (DAC) have been well characterized. Indeed, parkinsonian patients display visual impairments in early stages of the disease, including motion perception deterioration. Retinal cells responsible of motion perception are the directional selective ganglion cells (DSGC) which receive inhibitory synapses from starburst amacrine cells (SAC). Consequences of DAC degeneration in PD on the functionality of SAC and DSGC is unknown. In this work, we studied the functional connections between DAC and SAC in order to understand the pathophysiological mechanisms that determine the visual dysfunction in PD patients.Methods: Using immunohistochemistry and confocal imaging, we studied the retinal connections between DAC and SAC in wild‐type mice. To determine the type of Dopamine (DA) receptor expressed by SAC, we used transgenic mice whose cells expressing D1 or D2 receptors also express fluorescent markers. Intravitreal injections of 6‐OHDA were performed in a series of animals, followed by immunohistochemistry and optokinetic test.Results: We observed that DAC and SAC have direct synaptic contacts, and that the SAC located in the OFF sublamina of the inner plexiform layer express D2 receptors (D2R) but not D1 receptors. Moreover, depletion of DA in the 6‐OHDA injected mice induced a significant reduction of motion perception.Conclusions: This study shows for the first time in mice that the amacrine retinal cells responsible for perceiving directional selective moving stimuli express D2R. These findings provide new ways of detecting visual impairments in preclinical models of retinal DA degeneration.