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035 a| (Sirsi) o810216764;

035 a| (OCoLC)810216764;

040 a| EREc| EREd| EREd| UtOrBLW;

049 a| EREE;

100 1 a| Johnson, Tracy L.=| ^A1117038;

245 10 a| Dopaminergic modulation of the autonomic nervous system: in vitro and in vivo evidence from the mouse /c| by Tracy L. Johnson.;

260 a| [Greenville, N.C.] :b| East Carolina University,c| 2012.;

300 a| 135 pages :b| illustrations (color), digital, PDF file.;

336 a| text2| rdacontent;

337 a| computer2| rdamedia;

338 a| online resource2| rdacarrier;

490 1 a| ECU Brody School of Medicine thesis;

538 a| System requirements: Adobe Reader.;

538 a| Mode of access: World Wide Web.;

502 b| M.S.c| East Carolina Universityd| 2012.;

500 a| Presented to the faculty of the Department of Physiology.;

500 a| Advisor: Stefan Clemens.;

500 a| Title from PDF t.p. (viewed September 19, 2012).;

520 3 a| Central nervous system (CNS) function depends on both the connections between the underlying neurons and neural circuits and their activity. Neuronal activity in turn can be classified as neurotransmission and neuromodulation, where neuromodulation serves as a means to adapt neurotransmission to the different behavioral needs of the animal. Here, using the well-described monosynaptic stretch reflex (MSR) spinal circuit as a tool, we compared in the in vitro mouse spinal cord preparation the modulatory actions of DA in spinal lumbar segments that mediate somatosensory input and locomotor output with segments that additionally house the final common output of the autonomic nervous system (ANS). As the ANS contributes to the activation of the cardiac system and as a dysfunction of the DA system and the DA D3 receptor is associated with an increased prevalence of hypertension, we next addressed the potential role of DA modulation on the ANS in vivo, and in particular its role in hypertension and with age. In the first part of this thesis, we provide evidence that DA exerts opposing modulatory effects in ANS-containing segments when compared to segments void of ANS innervation and that this switch in DA modulation in the thoracic spinal cord is reversed by gap junction blockers. In the second part of the study, we show that aging-related increases in blood pressure and cardiac function in control wild-type (WT) animals were accompanied by bradycardia in the oldest animals. Interestingly, young D3 receptor knockout (D3KO) mice displayed blood pressure and heart rate values that were significantly increased over their age-matched WT controls but similar to those of the old WT group. Ultrasound echocardiography revealed aging-related increases in heart ventricle size in WT animals, but no similar changes in D3KO. In contrast, functional analyses revealed that ejection fraction and fractional shortening were compromised in old WT animals and similar to young D3KO mice. Subsequent histological assays demonstrated an aging-related interstitial fibrosis that peaked in old WT and that was similar to old WT in young D3KO mice. Taken together, our data suggest that DA-mediated neuromodulatory actions of spinal cord circuits are dependent on the underlying spinal circuitry, and they suggest that a dysfunction of the D3 receptor pathway is sufficient to mimic the increased hypertension and cardiac remodeling observed in the aging heart.;

504 a| Includes bibliographical references.;

650 2 a| Central Nervous System.=| ^A918663;

650 2 a| Dopaminex| physiology.=| ^A925861;

650 2 a| Neurotransmitter Agentsx| physiology.=| ^A948259;

650 2 a| Spinal Cord.=| ^A917896;

650 2 a| Autonomic Nervous System.=| ^A917860;

650 2 a| Mice.=| ^A921375;

650 2 a| Receptors, Dopamine D2.=| ^A1123471;

653 a| Neurosciences;

653 a| Physiology;

700 1 a| Clemens, Stefan.?| UNAUTHORIZED;

710 2 a| East Carolina University.b| Department of Physiology.?| UNAUTHORIZED;

830 0 a| ECU Brody School of Medicine thesis.=| ^A964744;

856 40 z| Access via ScholarShipu| http://hdl.handle.net/10342/4015;

949 a| Click on web addressw| ASISh| JOYNER101;

949 a| Click on web addressw| ASISh| HSL111;

994 a| C0b| ERE;

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998 a| 3108571;

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Dopaminergic modulation of the autonomic nervous system: in vitro and in vivo evidence from the mouse / by Tracy L. Johnson.

Author/creator	Johnson, Tracy L.
Other author	Clemens, Stefan.
Other author	East Carolina University. Department of Physiology.
Format	Theses and dissertations
Publication Info	[Greenville, N.C.] : East Carolina University, 2012.
Description	135 pages : illustrations (color), digital, PDF file.
Supplemental Content	Access via ScholarShip
Subjects	Central Nervous System. Dopamine--physiology. Neurotransmitter Agents--physiology. Spinal Cord. Autonomic Nervous System. Mice. Receptors, Dopamine D2.

Series	ECU Brody School of Medicine thesis ECU Brody School of Medicine thesis. ^A964744
Summary	Central nervous system (CNS) function depends on both the connections between the underlying neurons and neural circuits and their activity. Neuronal activity in turn can be classified as neurotransmission and neuromodulation, where neuromodulation serves as a means to adapt neurotransmission to the different behavioral needs of the animal. Here, using the well-described monosynaptic stretch reflex (MSR) spinal circuit as a tool, we compared in the in vitro mouse spinal cord preparation the modulatory actions of DA in spinal lumbar segments that mediate somatosensory input and locomotor output with segments that additionally house the final common output of the autonomic nervous system (ANS). As the ANS contributes to the activation of the cardiac system and as a dysfunction of the DA system and the DA D3 receptor is associated with an increased prevalence of hypertension, we next addressed the potential role of DA modulation on the ANS in vivo, and in particular its role in hypertension and with age. In the first part of this thesis, we provide evidence that DA exerts opposing modulatory effects in ANS-containing segments when compared to segments void of ANS innervation and that this switch in DA modulation in the thoracic spinal cord is reversed by gap junction blockers. In the second part of the study, we show that aging-related increases in blood pressure and cardiac function in control wild-type (WT) animals were accompanied by bradycardia in the oldest animals. Interestingly, young D3 receptor knockout (D3KO) mice displayed blood pressure and heart rate values that were significantly increased over their age-matched WT controls but similar to those of the old WT group. Ultrasound echocardiography revealed aging-related increases in heart ventricle size in WT animals, but no similar changes in D3KO. In contrast, functional analyses revealed that ejection fraction and fractional shortening were compromised in old WT animals and similar to young D3KO mice. Subsequent histological assays demonstrated an aging-related interstitial fibrosis that peaked in old WT and that was similar to old WT in young D3KO mice. Taken together, our data suggest that DA-mediated neuromodulatory actions of spinal cord circuits are dependent on the underlying spinal circuitry, and they suggest that a dysfunction of the D3 receptor pathway is sufficient to mimic the increased hypertension and cardiac remodeling observed in the aging heart.
General note	Presented to the faculty of the Department of Physiology.
General note	Advisor: Stefan Clemens.
General note	Title from PDF t.p. (viewed September 19, 2012).
Dissertation note	M.S. East Carolina University 2012.
Bibliography note	Includes bibliographical references.
Technical details	System requirements: Adobe Reader.
Technical details	Mode of access: World Wide Web.

Dopaminergic modulation of the autonomic nervous system: in vitro and in vivo evidence from the mouse / by Tracy L. Johnson.

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