Lateral hypothalamic neurotensin neurons orchestrate ingestive behaviors
"Food and water are necessary for survival but can only be obtained via ingestive behaviors (feeding, drinking and moving). Survival thus depends on the ability of the brain to coordinate the need for water and energy with appropriate behaviors to modify their intake as necessary for homeostasis. However, the balance of these behaviors also inherently determines body weight, and imbalances contribute to the development of weight disorders such as obesity and anorexia nervosa. The lateral hypothalamic area (LHA) of the brain is anatomically positioned to coordinate the sensation of osmotic and energy status with goal-directed ingestive behaviors necessary to maintain homeostasis and body weight, and, hence, may hold insight into potential treatment for energy balance disorders. This work was done to evaluate how neurotensin expressing LHA neurons (LHA Nts neurons) coordinate ingestive behaviors. The central hypothesis of this thesis was that the LHA neurotensin (Nts) neurons direct drinking behavior in response to physiologic need (thirst) via neural outputs to the lateral preoptic area (LPO), but do not modify feeding via LPO. The rationale for this hypothesis was that the LHA neurons promotes drinking, but suppresses feeding. In order to understand the nature of the drinking regulation by LHA Nts neurons, we experimentally activated LHA Nts neurons and studied drinking behavior under well-hydrated and dehydrated conditions. We observed that activation of LHA Nts neurons promotes voracious drinking of water and water-based solutions and with the given choice, animals prefer water and palatable solutions, regardless of the caloric content, rather than bitter and dehydrating solutions. We also found that activation increases the motivation to drink in well hydrated and thirsty animals beyond their perceived thirst. In addition, we showed that LHA Nts neural activation is not necessary for homeostatic and need based consumption. Furthermore, we mapped the connectivity of the LHA Nts neurons within the brain and provided a list of osmo- and energy-sensory and regulatory areas which are directly connected to LHA Nts neurons. Finally, we identified LHA Nts→LPO circuit that drives the drinking effect of LHA Nts neurons, but is not the route they suppress feeding. Overall, this work suggests that control of drinking and feeding by LHA Nts circuits is divergent and modulation of specific LHA Nts circuits may be useful therapeutic targets to treat dysregulated water intake."--Pages ii-iii.
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- In Collections
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Electronic Theses & Dissertations
- Copyright Status
- In Copyright
- Material Type
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Theses
- Authors
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Kurt, Gizem
- Thesis Advisors
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Leinninger, Gina M.
- Committee Members
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Mazei-Robison, Michelle
Robison, A.J
Johnson, Alexander W.
Olson, Karl
- Date
- 2019
- Program of Study
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Physiology - Doctor of Philosophy
- Degree Level
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Doctoral
- Language
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English
- Pages
- xvii, 187 pages
- ISBN
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9781392565018
1392565014
- Permalink
- https://doi.org/doi:10.25335/dmqz-v816