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

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	Development, validation, and use of a quantitative theory of in vivo dopamine dynamics./
Author:	Walters, Seth Holt.
Description:	1 online resource (145 pages)
Notes:	Source: Dissertation Abstracts International, Volume: 78-05(E), Section: B.
Subject:	Analytical chemistry. -
Online resource:	click for full text (PQDT)
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. - 1 online resource (145 pages)

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

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

Includes bibliographical references

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.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2018

Mode of access: World Wide Web

ISBN: 9781369418798Subjects--Topical Terms:

1182118
Analytical chemistry.
Index Terms--Genre/Form:

554714
Electronic books.

Development, validation, and use of a quantitative theory of in vivo dopamine dynamics.
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100 1 $a Walters, Seth Holt. $3 1186613
245 1 0 $a Development, validation, and use of a quantitative theory of in vivo dopamine dynamics.
264 0 $c 2016
300 $a 1 online resource (145 pages)
336 $a text $b txt $2 rdacontent
337 $a computer $b c $2 rdamedia
338 $a online resource $b cr $2 rdacarrier
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.
504 $a Includes bibliographical references
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.
533 $a Electronic reproduction. $b Ann Arbor, Mich. : $c ProQuest, $d 2018
538 $a Mode of access: World Wide Web
650 4 $a Analytical chemistry. $3 1182118
650 4 $a Neurosciences. $3 593561
655 7 $a Electronic books. $2 local $3 554714
690 $a 0486
690 $a 0317
710 2 $a ProQuest Information and Learning Co. $3 1178819
710 2 $a University of Pittsburgh. $3 1178873
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10298864 $z click for full text (PQDT)