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Abstract
One fundamental computation of retinal circuits is to reliably detect the direction of motion across variable visual conditions. This dissertation dives into the cellular and circuit mechanisms that establish and regulate direction-selective computation. My research focuses on activity-dependent metabotropic glutamate receptor 2 (mGluR2) signaling in starburst amacrine cells (SACs) and how this mechanism impacts the direction encoding by direction-selective ganglion cells (DSGCs). This work delineates how dendritic computation, synaptic integration and neuromodulatory control interact to maintain robust direction selectivity. I have used a combination of two-photon imaging, electrophysiology, pharmacology, immunohistochemistry and quantitative analysis in this study. This dissertation demonstrates that 1. direction-selective calcium signaling in distal dendrites of SACs is dynamically modulated by mGluR2 signaling (Chapter 2). I contributed to this work as a collaboration with a former graduate student Hector Acaron Ledesma. 2. Visually evoked glutamate release acutely modulates mGluR2 signaling. This leads to a shift in threshold of VGCC activation, thereby preserving direction selectivity in individual SAC dendrites under noisy visual conditions. This activity-dependent modulation of VGCCs allows for robust direction selectivity of SACs and extends the operating range of DSGC signaling in the presence of visual noise (Chapter 3). 3) During the developmental period of Postnatal day 9-11 when retinal waves show a temporal-to-nasal bias of propagation, neighboring SACs form mutual inhibitory synapses, but this connection does not show asymmetry along the nasal temporal axis. Therefore, SAC-SAC connectivity is not the cause of retinal wave propagation bias (Chapter 4). This work is part of a collaboration of Dr. Marla Feller’s lab at University of California at Berkeley, which aims to determine the neural basis of retinal wave propagation bias. Together, these findings highlight that dendritic integration is a dynamic process that can be acutely modulated based on the synaptic input. Activity-dependent dendritic computation in SACs enables the retinal direction selective circuit to reliably encode motion in the presence of background noise. Furthermore, during development, the directional bias of retinal wave propagation is independent of the developing SAC-SAC mutual connections.