Research into the location and operating characteristics of the neural substrates that control feeding behavior and energy expenditure is essential for an understanding of the basic physiology of intake control, and an appreciation of the CNS underpinnings of and treatments for obesity, anorexia, cachexia and other feeding pathologies. The field has been profoundly energized by a number of findings that have emerged in the past few years - from the discovery of leptin, and its central receptors to the identification of a variety of important neuropeptide mediators and their interactions. The findings have been cast firmly from a hypothalamic perspective, emphasizing leptin action on arcuate nucleus and in particular on those neurons with POMC and with NPY phenotype. It has become clear, however, that virtually all of the relevant control elements (e.g., leptin receptors, relevant neuropeptide receptors and cell bodies) are re-represented in the caudal brainstem. We propose to explore the contributions of brainstem substrates to the control of food intake and energy expenditure, with a focus on the performance of the chronic decerebrate rat (CD) relative to its neurologically intact control. Demonstrated competencies of the CD reflect the functional operation of circuits intrinsic to the brainstem. The principle measures include intake responses, core and brown-fat temperature, oxygen consumption, respiratory quotient, and heart rate. The responses are measured as functions of: (a) food deprivation and overfeeding, and (b) delivery of leptin and ghrelin, and neuropeptide (NPY, CRF, GLP1, melanocortin) receptor agonists and antagonists. In addition, changes in POMC and NPY mRNA expression in brainstem neurons is evaluated as a function of deprivation and leptin treatment. The proposed experiments should provide essential information about energy balance control functions that are endemic to the brainstem, and those functions that are served by an interaction between brainstem and hypothalamic structures.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK021397-28
Application #
6793630
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Yanovski, Susan Z
Project Start
1983-07-01
Project End
2008-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
28
Fiscal Year
2004
Total Cost
$352,771
Indirect Cost
Name
University of Pennsylvania
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Gerth, Ashlynn I; Alhadeff, Amber L; Grill, Harvey J et al. (2017) Regional influence of cocaine on evoked dopamine release in the nucleus accumbens core: A role for the caudal brainstem. Brain Res 1655:252-260
Kanoski, Scott E; Grill, Harvey J (2017) Hippocampus Contributions to Food Intake Control: Mnemonic, Neuroanatomical, and Endocrine Mechanisms. Biol Psychiatry 81:748-756
Ong, Zhi Yi; Liu, Jing-Jing; Pang, Zhiping P et al. (2017) Paraventricular Thalamic Control of Food Intake and Reward: Role of Glucagon-Like Peptide-1 Receptor Signaling. Neuropsychopharmacology 42:2387-2397
Alhadeff, Amber L; Holland, Ruby A; Zheng, Huiyuan et al. (2017) Excitatory Hindbrain-Forebrain Communication Is Required for Cisplatin-Induced Anorexia and Weight Loss. J Neurosci 37:362-370
Ong, Zhi Yi; Bongiorno, Diana M; Hernando, Mary Ann et al. (2017) Effects of Endogenous Oxytocin Receptor Signaling in Nucleus Tractus Solitarius on Satiation-Mediated Feeding and Thermogenic Control in Male Rats. Endocrinology 158:2826-2836
Alhadeff, Amber L; Golub, Danielle; Hayes, Matthew R et al. (2015) Peptide YY signaling in the lateral parabrachial nucleus increases food intake through the Y1 receptor. Am J Physiol Endocrinol Metab 309:E759-66
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Swick, Jennifer C; Alhadeff, Amber L; Grill, Harvey J et al. (2015) Parabrachial Nucleus Contributions to Glucagon-Like Peptide-1 Receptor Agonist-Induced Hypophagia. Neuropsychopharmacology 40:2001-14
Müller, T D; Nogueiras, R; Andermann, M L et al. (2015) Ghrelin. Mol Metab 4:437-60
Ong, Zhi Yi; Alhadeff, Amber L; Grill, Harvey J (2015) Medial nucleus tractus solitarius oxytocin receptor signaling and food intake control: the role of gastrointestinal satiation signal processing. Am J Physiol Regul Integr Comp Physiol 308:R800-6

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