Development and Function of Retinal Ganglion Cell Circuits

The function of our nervous system relies on specific patterns of synaptic connections between diverse neuronal cell types. My thesis research addressed how cell-type-specific patterns of connectivity emerge in the developing mouse retina and how they enable mature retinal neurons to detect specific sensory stimuli. Spike trains of the approximately 40 retinal ganglion cell (RGC) types in mammals encode specific features and events in the visual world, and are the sole source of visual information to the brain. Recent studies have begun to dissect the presynaptic circuits underlying diverse RGC light responses, but how cell-type-specific retinal circuits emerge during development is poorly understood. The first part of my dissertation explored the plasticity of the ON alpha (ONα-) RGC circuit. I found that developmental removal of the dominant excitatory input to ONα-RGCs triggers cell-type-specific rewiring, which precisely preserves ONα-RGCs’ characteristic light responses including high contrast sensitivity. Spiking neurons, including RGCs, typically encode sensory information by increasing firing rates in the presence of preferred stimuli. Suppressed-by-Contrast (SbC-) RGCs are unique in that they signal changes in luminance (i.e., contrast) by decreasing rather than increasing spiking. Taking advantages of mouse genetics, in the second part of my thesis, I characterized SbC-RGCs’ responses to complex stimuli and identified the synaptic mechanisms underlying their suppressive contrast encoding. Interestingly, I found that VGluT3-expressing amacrine cells (VG3-ACs) are dual transmitter neurons that release excitatory and inhibitory transmitters in a target-specific manner, and VG3-ACs specifically contributes to OFF inhibition to SbC-RGCs in response to small stimuli. Finally, using an intersectional transgenic approach, I preferentially labeled SbC-RGCs and mapped their central projections to explore the contribution of SbC-RGCs to vision