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osu1313104355.pdf (10.73 MB)
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Circuitry and function of mu opioid ligands in the rostral nucleus of the solitary tract and reticular formation
Author Info
Kinzeler, Nicole R.
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=osu1313104355
Abstract Details
Year and Degree
2011, Doctor of Philosophy, Ohio State University, Psychology.
Abstract
The rostral nucleus of the solitary tract (rNST) is ideally positioned in the medulla to receive and integrate incoming gustatory and somatosensory signals from the periphery and to communicate with several brainstem and forebrain regions involved in taste, feeding, and reward. The organization of the rNST is complex and the neurons in this region do not serve a single function. The rNST has two main outputs: the pontine parabrachial nucleus (PBN) and the subjacent medullary reticular formation (RF). These projections primarily arise from separate groups of rNST neurons and serve different functions. In particular, the RF houses the pattern generating circuitry necessary for generating stereotyped oromotor behaviors (licking vs. gaping). Gustatory input from the rNST strongly influences these behaviors, making the rNST and RF an important integrated unit. While it is known that both of these regions contain a variety of neurochemicals, their organization in the rNST and RF and their effects on ingestive behaviors are not well-characterized. This dissertation will focus on the behavioral impact and neural circuitry of one class of neuropeptides prominent in the rNST/RF, the endogenous mu opioids. Both of these regions contain the mu opioid receptor (MOR) and its endogenous ligands, the enkephalins (ENK) and the endomorphins (END). Experiments presented in Chapter 2 of this dissertation revealed that small, localized injections of a specific MOR agonist, D- Ala2, N-Me-Phe4, Gly-ol5-enkephalin (Damgo), in the rNST/RF significantly modulated oromotor behaviors. Specifically Damgo altered rate, amplitude, and duration of oromotor behaviors in a manner consistent with suppression of ingestion. Additionally, rNST/RF Damgo evoked a switch from licking to gaping in response to water. Clearly, exogenous MOR ligands act in the rNST and dorsal RF to evoke robust and complex behavioral effects. Although the identity of the endogenous ligand(s) mediating these effects has not been well-characterized, previous anatomical studies suggest ENK and END as possibilities. Moreover, while drug injections in our behavioral study were relatively confined, Damgo diffusion likely encompassed various cell-types and functionally distinct regions of the rNST and RF. Chapter 3 evaluated the distribution of ENK/END fibers and their interaction with four heterogeneous cell types in the rNST/RF (GABAergic, cholinergic, and RF and PBN projection), as well as their relationship to taste primary afferent terminal fields using the GAD67-EGFP knock-in mouse, and a combination of immunohistochemistry, retrograde tracing, and confocal microscopy. These experiments established a distinct topography for ENK and END fibers in the medial and ventral rNST. Opioid fibers shared an overlapping distribution with GABAergic and projection neurons in the ventral rNST and lateral ½ of the dorsal medial subfield. However, of all of the cell types examined, opioid fibers were most densely intermingled with cholinergic preganglionic parasympathetic neurons also residing in the medial rNST. Analysis of high magnification images supports close appositions between ENK/END fibers and these cholinergic neurons, supporting a role for mu opioids in autonomic function.
Committee
Susan Travers (Advisor)
Joseph Travers (Other)
Bennet Givens (Other)
Arthur White (Other)
Subject Headings
Behavioral Psychology
;
Neurobiology
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Citations
Kinzeler, N. R. (2011).
Circuitry and function of mu opioid ligands in the rostral nucleus of the solitary tract and reticular formation
[Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1313104355
APA Style (7th edition)
Kinzeler, Nicole.
Circuitry and function of mu opioid ligands in the rostral nucleus of the solitary tract and reticular formation.
2011. Ohio State University, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=osu1313104355.
MLA Style (8th edition)
Kinzeler, Nicole. "Circuitry and function of mu opioid ligands in the rostral nucleus of the solitary tract and reticular formation." Doctoral dissertation, Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1313104355
Chicago Manual of Style (17th edition)
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Document number:
osu1313104355
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322
Copyright Info
© 2011, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.