Mapping the neural basis of motivated behavior

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Abstract/Contents

Abstract
Understanding what in the brain establishes specific motivational states, and how these states cause animals to pursue particular goal-directed behaviors, are central goals of behavioral neuroscience. Fully determining the mechanisms underlying these processes will require a comprehensive description of how the brain operates at different levels spanning multiple spatial and temporal scales, from the expression of individual genes within single cells to the coordinated activity of brain-wide networks of neurons. As a step towards this ultimate goal, this dissertation proposes several new approaches to map and understand the structural, functional, and molecular properties of neural circuits. These approaches are applied to study the circuits underlying motivated behavior, with an emphasis of thirst motivation. This work is divided into several parts. (1) I de-scribe the application of a method for labeling neural circuits defined by activity (TRAP) in combination with whole-brain clearing and imaging technology to map the location of neurons activated by a particular experience throughout the brain, and study their structural and molecular properties. (2) Extending the idea of brain-wide imaging to study dynamics, I introduce two new approaches to perform large-scale in vivo imaging of neural activity across the surface of the mouse brain, to study cell-type-specific cortical dynamics involved in production of a simple thirst-motivated choice behavior. (3) I dis-cuss an improved approach to TRAP, and apply this technique to measure and manipulate a crucial node in the neural circuit underlying the sensation of thirst to reveal how activity in this circuit induced by water deprivation produces an aversive drive that is diminished through water consumption. (4) I develop a new approach to spatially map the expression of up to 1,000 genes simultaneously in three dimensions within single cells in a tissue section, and show that this approach is compatible with activity measurement using activity regulated genes as a post hoc reporter of neural activity. (5) Finally, I develop an approach using large-scale electrophysiology to study spatially-localized activity dynamics from cells distributed throughout the entire mouse brain. I apply this technique to study brain-wide neural dynamics during thirst motivated choice behavior, revealing how thirst motivational state is represented throughout the brain and how this state gates the flow of information from sensory to motor regions.

Description

Type of resource text
Form electronic resource; remote; computer; online resource
Extent 1 online resource.
Place California
Place [Stanford, California]
Publisher [Stanford University]
Copyright date 2019; ©2019
Publication date 2019; 2019
Issuance monographic
Language English

Creators/Contributors

Author Allen, William Edward
Degree supervisor Deisseroth, Karl
Degree supervisor Luo, Liqun, 1966-
Thesis advisor Deisseroth, Karl
Thesis advisor Luo, Liqun, 1966-
Thesis advisor Hestrin, Shaul
Thesis advisor Newsome, William T
Thesis advisor Shenoy, Krishna V. (Krishna Vaughn)
Degree committee member Hestrin, Shaul
Degree committee member Newsome, William T
Degree committee member Shenoy, Krishna V. (Krishna Vaughn)
Associated with Stanford University, Neurosciences Program.

Subjects

Genre Theses
Genre Text

Bibliographic information

Statement of responsibility William Edward Allen.
Note Submitted to the Neurosciences Program.
Thesis Thesis Ph.D. Stanford University 2019.
Location electronic resource

Access conditions

Copyright
© 2019 by William Edward Allen

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