Circuit function and visual signal processing in the retina

National Institute Of Neurological Disorders And Stroke

Investigators

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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 studied closely the rod pathway, specifically the synaptic inputs to and outputs from A2 amacrine cells. Recent work from other labs has shown that rod bipolar cells (RBC), which provide excitatory input to A2s, receive presynaptic inhibition primarily from a wide-field GABAergic amacrine cell driven by other RBCs. We hypothesize that this surround inhibition modulates the gain and dynamic range of RBC-A2 signaling, enabling the A2 to integrate signals effectively in the mid-scotopic visual range. We have recorded visually evoked signals in A2s in the dark-adapted whole-mount retina preparation to examine the effects of this feedback inhibition on visual signaling. Our results indicate that this feedback inhibition modulates synaptic signaling under mesopic and photopic conditions, but not under very low light (scotopic) levels. Further experiments indicate that nNOS-1 amacrine cells mediate feedback inhibition under mesopic conditions but that some other amacrine cell contributes at higher light levels. Moreover, we have discovered that s-ON alpha ganglion cells (RGCs) inherit this surround inhibition from AIIs via AII gap junction connections with ON cone bipolar cells presynaptic to the s-ON alpha RGCs. We have undertaken a machine learning approach to identifying individual SACs within the dense plexus of fluorescent processes in the ChAT-tdTomato mouse retina. We have successfully developed an algorithm to segment individual neurons from a field containing several other overlapping SACs. A graduate student in the lab is extending this approach to other cell types. A manuscript has been published this year and another has been submitted. We have completed a detailed serial EM morphological analysis of Muller cells that has revealed previously unappreciated arrangements of Muller cells with respect to the retinal vasculature. The EM data also indicate gaps in the Muller cell coverage that permit neuronal contact with underying pericytes. Imaging experiments reveal calcium signals in Muller processes surrounding capillaries in all retinal vascular layers. A manuscript is in preparation. Experiments are underway to examine physiological consequences of this interesting morphology. We are also examining circuit mechanisms that influence the sensitivity of light responses in dopamine amacrine cells and two common RGCs. We find that inhibitory mechanisms differentially modulate outputs from bipolar cells that influence diffferent RGCs distinctly.