Circuit function and visual signal processing in the retina

National Institute Of Neurological Disorders And Stroke

Investigators

Linked publications, trials & patents

Abstract

Our work focuses on specialized circuitry in the inner retina. Having examined several inner retinal synapses in physiological detail, we now seek to understand how these synapses contribute to visual processing in the surrounding circuitry. We have completed a detailed serial EM morphological analysis of Müller cells that has revealed previously unappreciated arrangements of Müller cells with respect to the retinal vasculature. The EM data also indicate gaps in the Müller cell coverage that permit neuronal contact with underlying pericytes. Imaging experiments reveal calcium signals in Müller processes surrounding capillaries in all retinal vascular layers. Interestingly, the ultrastructural relationship between the Müller cells and vessels is compromised in a layer-specific fashion in a mouse model of retinitis pigmentosa. This work was published this year (Grimes, et al., 2025, Curr. Biol.). We are also examining circuit mechanisms that influence the sensitivity of light responses in dopamine amacrine cells (DACs) and two common RGCs. We find that inhibitory mechanisms differentially modulate outputs from bipolar cells that influence different RGCs distinctly. This work is being prepared for publication. In a collaborative project, we have examined the distribution of DACs in different species (Miyagishima, et al., 2025, Int. J. Mol. Sci.). We also have recorded light evoked responses in DACs that are mediated by intrinsically photosensitive ganglion cells. Further experiments are required, but this project is on track for publication soon. Collaborations with researchers in NIMH have focused on the circuit and cellular physiology of intrinsically photosensitive retinal ganglion cells (ipRGCs). We have examined the sensitivity of these cells to different visual stimuli and the conditions under which these cells enter into depolarizing block. These results have been submitted for publication and are currently at the revision stage. In a collaborative project with researchers in Tübingen, Germany, we have investigated the circuit mechanism underlying object motion processing by retinal ganglion cells. Behavioral and population calcium imaging experiments in mice have been followed up with whole-cell recordings from single ganglion cells. These experiments show that both the excitatory and inhibitory inputs to ganglion cells encode both object and background motion. Moreover, our results show that excitatory inputs to ON ganglion cells encode most motion information, whereas inhibitory inputs to OFF ganglion cells encode the most information. These experiments are currently being written up for publication.