Circuit function and visual signal processing in the retina

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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. Much of our previous work has centered on signaling in the rod pathway, specificically 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 are recording visually evoked signals in A2s in the dark-adapted whole-mount retina preparation to examine the effects of this feedback inhibition on scotopic signaling. We have studied how A17 amacrine cells contribute to scotopic signaling (e.g., Oesch and Diamond, 2020, Vis. Neurosci.), and we are interested to know the relative roles of these two amacrine cell subtypes. We are continuing our examination of starburst amacrine cell (SAC) function in the mouse retina by undertaking a machine learning approach to identifying individual SACs within the dense plexus of fluorescent processes in the ChAT-tdTomato mouse retina. Our goal is to record Ca signals in all of the output synapses within the SAC network, then use the machine learning algorithms to associate each synapse with its respective SAC. This project is progressing well, and we are in the process of recording visual responses from groups of SACs that can be morphologically distinguished from each other. We are also examining a novel mechanism by which a single, densely expressed amacrine cell type may provide the link between light evoked activity and control of the retinal vasculature. We are combining electrophysioogical, imaging and connectomic approaches to examine the circuit connectivity and function of this amacrine cell. Our work, following up on other work in the field (primarily by Eric Newman) also suggests that Mller cells, radially oriented glial cells in the retina, play a critical role in retinal neurovascular coupling. We have undertaken a detailed morphological analysis of Mller cell using serial EM data sets, which provide access to Mller cell morphology with unprecedented resolution. This has revealed previously unappreciated arrangements of Mller cells with respect to the retinal vasculature.