Mechanisms and circuitry underlying direction selectivity in the mouse retina
Date
2022-04-28
Authors
Hanson, Laura
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Abstract
Vision is a key sensory modality that is essential for survival. In the vertebrate visual system, light signals detected by photoreceptors are highly processed in the retina itself before being relayed to higher-order visual areas. The retina decomposes visual signals into specific features such as contrast, size, orientation, direction and/or velocity and relays this information via distinct output ganglion cells. For example, the direction-selective ganglion cells (DSGCs) are responsible for encoding the direction of objects moving across the retina. This may occur due to self-motion or as objects move through the environment. DSGCs respond robustly for motion of a particular “preferred” direction while exhibiting little to no response during motion in the opposite or “null” direction.
In this dissertation, I examined the synaptic mechanisms involved in generating direction selectivity, both at the level of the DSGC as well as in the dendrites of presynaptic GABAergic/cholinergic starburst amacrine cell, where direction selectivity is first observed. Using mouse genetics to selectively disrupt direction processing capabilities of starburst dendrites, I revealed a second mechanism for generating direction selectivity. This relies on the differential functional wiring of GABA and ACh to DSGCs, which provides a substrate for directional dependent changes in the timing of excitation and inhibition to DSGCs (Chapter 2).
In chapters 3 and 4, I turned my focus to the excitatory glutamatergic inputs to the DSGCs mediated by bipolar cells (that bridge the photoreceptor to output ganglion cells). Specifically, I examined the organization and AMPA and NMDA receptor composition (Chapter 3). By analyzing the spontaneous excitatory activity in the DSGC in combination with 2-photon imaging of the NMDA mediated calcium responses and glutamate signaling, I show the ‘silent’ NMDA-rich synapses are able to encode information across a range of contrasts.
Finally, I also examined how the bipolar cell output to DSGCs is asymmetrically modified by another class of amacrine cell: the wide-field amacrine cells. In Chapter 4, I discovered that the subtype of nasal coding ON-OFF DSGCs are also orientation-selective (OS)-they respond best to vertically oriented bars. I show this selectivity originates at the level of bipolar cell axon terminals, which appear to be gap junction coupled to the vertically orientated processes of wide field amacrine cells. These finding led me to propose that orientation tuning in bipolar cells may act as a filter to simplify the task of encoding direction of motion for moving edges in the DSGC. This research highlights the mechanisms and circuitry required for the retina to accurately encode the direction of motion across the visual scene and provides us with a deeper understanding of the circuitry and mechanisms involved in direction selectivity in the mouse retina.