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You searched for +publisher:"University of North Carolina" +contributor:("Wetsel, William"). One record found.

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University of North Carolina

1. Rogan, Sarah. Remote Control of Neuronal Signaling in vivo.

Degree: Pharmacology, 2011, University of North Carolina

A significant challenge for neuroscientists is to determine how both electrical and chemical signals affect the activity of cells and circuits and how the nervous system subsequently translates that activity into behavior. Remote, bidirectional manipulation of those signals with high spatiotemporal precision is an ideal approach to addressing that challenge. Recently, neuroscientists have developed a diverse set of tools that permit such experimental manipulation with varying degrees of spatial, temporal, and directional control. These tools use light, peptides, and small molecules to primarily activate ion channels and G protein-coupled receptors (GPCRs) that in turn activate or inhibit neuronal firing. By monitoring the electrophysiological, biochemical, and behavioral effects of such activation/inhibition, researchers can better understand the links between brain activity and behavior. The research in this thesis centers on using a class of designer GPCRs, termed Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), to remotely and non-invasively control the activity of particular neuronal populations. DREADDs are evolved muscarinic receptors that selectively respond to the otherwise inert compound clozapine-N-oxide (CNO) and not to their native ligand, acetylcholine. Using a chemical-genetic approach, I demonstrate that the Gq-coupled DREADD (hM3Dq), which is derived from the human muscarinic M3 receptor, can be used to activate neuronal firing selectively in the cortex and hippocampus of mice expressing hM3Dq. The neuronal activation subsequently results in behavioral and electrophysiological changes. Then, I use those behavioral changes as a readout to examine the underlying neurocircuitry and discuss the findings in the context of psychosis. The tools for remote control of neuronal activity, including DREADDs, differ in the direction of their effect (activation/inhibition, hyperpolarization/depolarization), their onset and offset kinetics (milliseconds/minutes/hours), the degree of spatial resolution they afford, and their invasiveness. While none of these tools is perfect, they each have advantages and disadvantages, which I describe, and they are all still works-in-progress. I conclude with a discussion of the clinical and translational applications of these technologies and provide suggestions for improving upon the existing tools. Advisors/Committee Members: Rogan, Sarah, Roth, Bryan, Siderovski, David P., Harden, T. Kendall, Wetsel, William, Malanga, C. J..

Subjects/Keywords: School of Medicine; Department of Pharmacology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Rogan, S. (2011). Remote Control of Neuronal Signaling in vivo. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:0172af27-f131-4573-b8f3-1523d34c3b79

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Rogan, Sarah. “Remote Control of Neuronal Signaling in vivo.” 2011. Thesis, University of North Carolina. Accessed December 04, 2020. https://cdr.lib.unc.edu/record/uuid:0172af27-f131-4573-b8f3-1523d34c3b79.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Rogan, Sarah. “Remote Control of Neuronal Signaling in vivo.” 2011. Web. 04 Dec 2020.

Vancouver:

Rogan S. Remote Control of Neuronal Signaling in vivo. [Internet] [Thesis]. University of North Carolina; 2011. [cited 2020 Dec 04]. Available from: https://cdr.lib.unc.edu/record/uuid:0172af27-f131-4573-b8f3-1523d34c3b79.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Rogan S. Remote Control of Neuronal Signaling in vivo. [Thesis]. University of North Carolina; 2011. Available from: https://cdr.lib.unc.edu/record/uuid:0172af27-f131-4573-b8f3-1523d34c3b79

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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