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Development, validation, and use of ...

Walters, Seth Holt.

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Development, validation, and use of a quantitative theory of in vivo dopamine dynamics.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Development, validation, and use of a quantitative theory of in vivo dopamine dynamics./
Author:	Walters, Seth Holt.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2016,
Description:	145 p.
Notes:	Source: Dissertation Abstracts International, Volume: 78-05(E), Section: B.
Contained By:	Dissertation Abstracts International78-05B(E).
Subject:	Analytical chemistry. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10298864
ISBN:	9781369418798

Development, validation, and use of a quantitative theory of in vivo dopamine dynamics.
Walters, Seth Holt.

Development, validation, and use of a quantitative theory of in vivo dopamine dynamics. - Ann Arbor : ProQuest Dissertations & Theses, 2016 - 145 p.

Source: Dissertation Abstracts International, Volume: 78-05(E), Section: B.

Thesis (Ph.D.)--University of Pittsburgh, 2016.

Since the early 1980s, fast scan cyclic voltammetry (FSCV) has been used to detect changes in dopamine's presence in the brain's extracellular space. The dopamine signals detected result from several simultaneous biophysical processes. Because these processes currently cannot be directly measured, a mathematical model which quantitatively explains FSCV data is necessary to describe their natures and magnitudes. I have created a simple mathematical model which posits that diffusion of dopamine in the brain follows a unidirectional first order kinetic scheme from its source. The model, using just three parameters, produces excellent fits to dopamine responses evoked by short electrical stimuli. These parameters are: Rp (release), kU (uptake) and kT (mass transport). When longer stimulations are performed, the addition of a term kR, which modifies Rp by an exponential, is adequate to fit nearly all observed dopamine responses in the anaesthetized rat brain.

ISBN: 9781369418798Subjects--Topical Terms:

3168300
Analytical chemistry.

Development, validation, and use of a quantitative theory of in vivo dopamine dynamics.
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100 1 $a Walters, Seth Holt. $3 3347023
245 1 0 $a Development, validation, and use of a quantitative theory of in vivo dopamine dynamics.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2016
300 $a 145 p.
500 $a Source: Dissertation Abstracts International, Volume: 78-05(E), Section: B.
500 $a Adviser: Adrian C. Michael.
502 $a Thesis (Ph.D.)--University of Pittsburgh, 2016.
520 $a Since the early 1980s, fast scan cyclic voltammetry (FSCV) has been used to detect changes in dopamine's presence in the brain's extracellular space. The dopamine signals detected result from several simultaneous biophysical processes. Because these processes currently cannot be directly measured, a mathematical model which quantitatively explains FSCV data is necessary to describe their natures and magnitudes. I have created a simple mathematical model which posits that diffusion of dopamine in the brain follows a unidirectional first order kinetic scheme from its source. The model, using just three parameters, produces excellent fits to dopamine responses evoked by short electrical stimuli. These parameters are: Rp (release), kU (uptake) and kT (mass transport). When longer stimulations are performed, the addition of a term kR, which modifies Rp by an exponential, is adequate to fit nearly all observed dopamine responses in the anaesthetized rat brain.
520 $a To complement this work, I have determined that the ubiquitous failure of dopamine concentration changes as measured by FSCV to return to baseline, called hang-up, is an artifact caused by a form of long duration adsorption to the carbon fiber electrodes commonly used to measure dopamine. I have developed a mathematical correction for this artifact. In addition, I have experimentally determined that the observed first order behavior of the mass transport parameter kT arises essentially entirely from the brain itself, rather than the adsorption kinetics of dopamine at the electrode.
520 $a Finally, having established a sound theoretical framework for understanding the biological and instrumental origins of dopamine signals in the brain, I have used this model to study both anatomical differences in dopamine signaling, as well as the biophysical effects of the drug bupropion, an antidepressant. These studies have found that the density of dopamine signaling is greatest in the dorsolateral striatum, and that this high density of signaling is enabled by high rates of dopamine uptake, which attenuate the spatial range of dopamine signaling. I anticipate that this work is a necessary step towards the comprehensive mechanistic dissection of cellular signaling, and I hope it will prove invaluable to future progress.
590 $a School code: 0178.
650 4 $a Analytical chemistry. $3 3168300
650 4 $a Neurosciences. $3 588700
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710 2 $a University of Pittsburgh. $3 958527
773 0 $t Dissertation Abstracts International $g 78-05B(E).
790 $a 0178
791 $a Ph.D.
792 $a 2016
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10298864