2002 — 2004 |
Baird, John-Paul |
R03Activity Code Description: To provide research support specifically limited in time and amount for studies in categorical program areas. Small grants provide flexibility for initiating studies which are generally for preliminary short-term projects and are non-renewable. |
Taste and Visceral Integration in Parabrachial Nucleus
DESCRIPTION (provided by applicant): Feeding and metabolic disorders such as obesity, anorexia, bulimia, gastroesophageal reflux cachexia, dysgeusia, and anosmia contribute to numerous diseases including hypertension, stroke, diabetes, and heart disease, and thus account for a large proportion of health- care costs in North America and other countries. Elucidating the neural mechanisms that control feeding is, therefore, of fundamental clinical significance. Numerous behavioral studies indicate that feeding is regulated by the integration of taste and visceral afferent signals within the central nervous system; however, only a handful of neurophysiological studies have attempted to locate and characterize these mechanisms. This application will evaluate neural interactions between gustatory and visceral afferent signals in the parabrachial nucleus (PBN), a brainstem relay that receives significantly overlapping taste and visceral afferent inputs. The first experiments will use standard neurophysiological recording techniques to test the hypothesis that duodenal nutrient and distension signals are represented in PBN, as they have not been described at this level, and that these signals interact with gastric distension responses. The interaction of duodenal-signals with gastric distension and gustatory responses in PBN will then be neurophysiologically evaluated to test the hypothesis that a concomitant of satiation is expressed in the form of visceral suppression of palatable taste responses in PBN. The final phase of this application will further explore the visceral modulation of PBN taste responses through an attempt to identify whether particular neurotransmitters play a role in mediating the effect. Specifically, neurotransmitter antagonists will be microinjected into the discrete vicinity of single taste cells as they are recorded during visceral and taste stimulation. It is hypothesized that if the suppression of taste responses by visceral stimuli is mediated locally by the neurotransmitter in question, then antagonism of its receptor systems should reverse the taste suppression effect. Identifying the neurotransmitters that participate in the visceral suppression of taste responses in PBN may also provide insight regarding other central mechanisms that participate in feeding control.
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2005 — 2011 |
Baird, John-Paul |
R15Activity Code Description: Supports small-scale research projects at educational institutions that provide baccalaureate or advanced degrees for a significant number of the Nation’s research scientists but that have not been major recipients of NIH support. The goals of the program are to (1) support meritorious research, (2) expose students to research, and (3) strengthen the research environment of the institution. Awards provide limited Direct Costs, plus applicable F&A costs, for periods not to exceed 36 months. This activity code uses multi-year funding authority; however, OER approval is NOT needed prior to an IC using this activity code. |
Role of Parabrachial Nucleus Neuropeptides in Feeding
DESCRIPTION (provided by applicant): Advances in obesity treatment may be provided by continued resolution of the neural circuits that mediate leptin, ghrelin, and insulin responses. Considerable recent research has detailed first and second order sites in hypothalamic regions that are sensitive to leptin, insulin, and ghrelin input. Forebrain neurons expressing neuropeptides throughout the brain are sensitive to these hormones and act as downstream mediators to influence feeding and metabolism. These neuropeptides, such as neuropeptide Y (NPY), and orexin-A (ORX), and pro- opioimelanocortin products (MC), act or have receptors in forebrain and hindbrain locations. An important goal for future research is to determine how such neuropeptides function in brainstem nuclei and to determine how these nuclei interact with forebrain nuclei (e.g., hypothalamus) that are sensitive to leptin, ghrelin, and insulin. This proposal will continue to evaluate the effects of NPY, MC, and ORX receptor ligands on feeding and electrophysiological taste and visceral responses in the pontine parabrachial nucleus (PBN), a brainstem nucleus that receives significantly overlapping taste and visceral afferent inputs, receives direct NPY, MC, and ORX input from the hypothalamus, and sends output to brainstem nuclei controlling oral movement. The first experiments assess the effects of direct PBN microinjectons of NPY, MC, and ORX receptor antagonists on feeding microstructure. The following experiments assess the effects of NPY, MC, and ORX receptor antagonists on neural PBN gustatory and gastric distension responses when NPY, MC, and ORX agonists are applied to brain ventricles or their antagonists are microinjected directly around PBN neurons. If direct PBN application of NPY, MC, or ORX receptor ligands affect feeding, this should be observed at the neurophysiological level and will serve to better clarify the functional role(s) of hypothalamic neuropeptides in the brainstem. PUBLIC HEALTH RELEVANCE Feeding and metabolic disorders such as obesity, anorexia, bulimia, failure to thrive, gastric reflux, cachexia, early satiety, delayed gastric emptying, dysgeusia, and anosmia contribute to diseases including hypertension, stroke, diabetes, and heart disease, and they account for many health-care costs. Elucidating the neural systems that control feeding is, therefore, a fundamental goal for clinical as well as basic science. This proposal will continue to explore the role of the brainstem as a site of feeding-related hypothalamic neuropeptide action and thus contribute to basic research that could help to identify potential pharmacological therapeutic targets.
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