Date on Master's Thesis/Doctoral Dissertation

5-2023

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Anatomical Sciences and Neurobiology

Degree Program

Anatomical Sciences and Neurobiology, PhD

Committee Chair

Borghuis, Bart

Committee Co-Chair (if applicable)

Bickford, Martha

Committee Member

Bickford, Martha

Committee Member

Gregg, Ron

Committee Member

McCall, Maureen

Committee Member

Stirling, David

Author's Keywords

retina; mouse; orientation; neuroscience; circuitry; classification

Abstract

Retinal Ganglion Cells (RGCs) form functionally distinct signaling channels that selectively encode features of the visual input including direction of motion, contrast polarity, size, and color. A highly conserved visual channel amongst vertebrates conveys orientation selectivity, i.e., the selective firing of neuronal cells in response to elongated stimuli along a preferred orientation. Orientation selectivity is an apparent critical computation and several studies have reported aspects of it, including cell type identity in anatomical reconstructions, and functional characterization of at least four different identified RGC types. But how cell types in the different studies relate is not well resolved; the mechanisms that generate the orientation selective responses in mice remain incompletely understood; and the retinofugal projections of OS RGC types are unknown. The goal of this study was to comprehensively characterize Orientation Selective (OS) RGC types in the mouse retina, and to elucidate the mechanisms that contribute to their tuning properties. We used population calcium imaging and hierarchical clustering to identify orientation selective RCGs in retinal explants. We then targeted these cells for detailed morphological and electrophysiological study. Our survey of RGC populations and subsequent morphological analysis distinguished 10 morphological types with apparent OS tuning. Electrophysiological analysis of 5 types identified specific tuning mechanisms, including a type with tuned excitation and inhibition, and a type with just tuned inhibition. Retrograde tracing from dLGN indicates that OS cells project to the shell region of the dorsal Lateral Geniculate Nucleus (dLGN), indicating that at least some OS RGC types contribute to dLGN OS tuning. This work provides new insight into the morphology and function of RGC types that exhibit OS properties. Additional studies will be necessary to further solidify the full complement of OS types in the retina and resolve their detailed circuit-level mechanisms, synaptic partners, molecular profiles, and retinofugal projections.

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