Mechanisms of neuronal computation in the visual system

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Abstract/Contents

Abstract
Neuronal circuits perform stepwise transformations of sensory input to extract critical information about the environment. This information then ultimately guides behavior, making these computations essential for the organism's survival. Specifically, what are the computations that neuronal circuits perform? What are the circuit and molecular mechanisms that implement them? The work presented in this dissertation addresses these questions in the early visual system of the fruit fly Drosophila melanogaster. By combining two-photon imaging of neuronal voltage and calcium signals with genetic manipulations, I have dissected the mechanisms underlying several core transformations in visual processing. In Chapter 1, I review elementary motion detection in Drosophila, the critical computation by which visual motion is first computed and is therefore a paradigmatic computation for neural processing more broadly. This chapter also serves as an introduction to the Drosophila visual system, as I discuss the anatomy and physiology of a number of neurons, including those that I studied. Following the introduction, my dissertation contains three chapters documenting the primary research projects that I have worked on during my doctoral training. Dynamic changes in membrane potential and intracellular calcium concentrations in axons and dendrites implement neuronal computations. However, as it has been challenging to measure membrane potential in neurites in vivo, how these signals are transformed as information flows through neurons and across synapses remains incompletely understood. Genetically encoded voltage indicators are promising tools for functional characterization of membrane potential changes with subcellular resolution. Chapter 2 describes the development and validation of the novel voltage indicator ASAP2 in vitro as well as in vivo in the Drosophila visual system. Chapter 3 expands upon this work and uses two-photon imaging of both voltage and calcium to reveal neuronal computations in the Drosophila visual system, including the origin of ON and OFF selectivity. I next asked about the circuit and molecular mechanisms that implement these computations. This required manipulation of gene function with cell type specificity, but the techniques for doing so in Drosophila often reduced gene activity incompletely. Chapter 4 describes the development of an improved tool for conditional gene disruption and the demonstration of its utility for investigating how individual genes contribute to neuronal function in vivo. My dissertation additionally includes two appendices. Appendix A reviews genetically encoded voltage indicators, focusing on the properties that determine indicator performance and the biological questions that these tools are primed to address. Appendix B is an eLife Insight piece commenting on Seeds et al., 2014.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2017
Issuance monographic
Language English

Creators/Contributors

Associated with Yang, Helen Horan
Associated with Stanford University, Neurosciences Program.
Primary advisor Clandinin, Thomas R. (Thomas Robert), 1970-
Thesis advisor Clandinin, Thomas R. (Thomas Robert), 1970-
Thesis advisor Baccus, Stephen A
Thesis advisor Goodman, Miriam Beth
Thesis advisor Luo, Liqun, 1966-
Advisor Baccus, Stephen A
Advisor Goodman, Miriam Beth
Advisor Luo, Liqun, 1966-

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Helen Horan Yang.
Note Submitted to the Program in Neurosciences.
Thesis Thesis (Ph.D.)--Stanford University, 2017.
Location electronic resource

Access conditions

Copyright
© 2017 by Helen Horan Yang
License
This work is licensed under a Creative Commons Attribution Non Commercial No Derivatives 3.0 Unported license (CC BY-NC-ND).

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