1977 — 1984 |
Pfaffmann, Carl Norgren, Ralph |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Gustatory and Visceral Afferent Neural Organization |
1 |
1985 — 2009 |
Norgren, Ralph |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Neural Systems of Ingestive Behavior @ Pennsylvania State Univ Hershey Med Ctr
DESCRIPTION: The proposed research continues an investigation of the neural mechanisms that govern the decision to ingest or reject the contents of the oral cavity. The neural substrates are located in the brainstem. Afferent activity (gustatory, thermal,tactile) that initiates and guides ingestion reaches the medulla and pons first. The response elicited by these stimuli can be switched from ingestion to rejection by vagal visceral activity that reaches the CNS first in the medulla. Likewise, the oral motor neurons and the interneurons projecting to them are found in the brainstem. The behavior of chronic precollicular decerebrate rats provides confirmation of the sufficiency of caudal brainstem mechanisms for ingestion and rejection responses. The proposed experiments use behavioral and electrophysiological techniques to test hypotheses about the function of the nucleus of the solitary tract (NST) and the parabrachial nucleus (PBN) in processing gustatory and visceral afferent information and examining the responses of oral motor interneurons during ingestion. There are three specific aims: First focal lesions will be used in CD rats to evaluate the contribution of the NST, PBN and the parvicellular reticular formation (RF) subjacent to the NST to simple and complex gustatory functions. CD rats with bilateral PBN lesions will be tested for responses to sucrose and for the effects of satiety. Rats with lesions of the anterior NST or parvicellular RF will be tested for preference - aversion functions, learned taste aversions and bodyweight regulation. Animals with lateral hypothalamic lesions will also be tested for the ability to acquire learned taste aversions and to express sodium appetite. For the second specific aim, electrophysiological studies are proposed in awake, behaving rats. Neural responses will be recorded in the NST and PBN for the effects of conditioned taste aversions and duodenal infusions of lipids, since it is clear that both experiences and immediate physiological conditioning can influence ingestion and rejection behavior. Medullary reticular formation neurons will be tested for responses to water, sapid stimuli and liquid diet. Oral motor interneurons in the RF that are found to respond differentially to the sensory characteristics of oral stimuli will be tested during more complex taste-guided behaviors. Experiments related to the third specific aim will examine the neural relationships among brainstem and fore brain areas implicated in the control of ingestive behavior. Neural responses will again be recorded in awake behaving animals. Electrical stimulation of the lateral hypothalamus, amygdala or bed nucleus of the stria terminalis will be used to alter the firing patterns of gustatory and oral motor interneurons in the brainstem.
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1 |
1986 — 2000 |
Norgren, Ralph |
K02Activity Code Description: Undocumented code - click on the grant title for more information. K05Activity Code Description: For the support of a research scientist qualified to pursue independent research which would extend the research program of the sponsoring institution, or to direct an essential part of this research program. |
Neural Systems of Taste and Ingestive Behavior @ Pennsylvania State Univ Hershey Med Ctr
This proposal represents a synthesis of research concerned with the neural mechanisms that underlie the sensory control of feeding behavior. In large part, the short term control of ingestive behavior is governed by sensory neural processes originating in the oral cavity and viscera. Gustatory stimuli offer a unique sensory probe of this system, because easily specifiable chemical stimuli reliably elicit ingestion or rejection. Visceral afferent stimuli can modulate gustatory activity within the brain such that the behavioral response to the same chemical stimulus is switched from ingestion to rejection, or vice versa. This proposal focuses on two areas, the caudal brainstem and the thalamo-cortical axis. The caudal brainstem, the medulla, pons, and midbrain, contains the first central synapses for both gustatory and vagal visceral afferent axons, the motoneurons responsible for ingestive behavior, and sufficient integrative compacity to support rudimentary hunger and satiety. In the forebrain, the sensory control of ingestion is equally well documented, but the neural mechanisms involved are poorly understood. The anatomy of the gustatory system has been established, but the neural procesisng of taste information in the forebrain remains obscure. For the visceral afferent system, not even the central organizaation can be specified. Using neuroanatomical, electrophysiological, and behavioral analysis, specific experiments will examine (1) the function of oral sensory activity in eliciting and guiding ingestion and rejection behavior, (2) the nature of the visceral events that control these response, and (3) the organization, coding, and integration of the gustatory and visceral afferent activity involved in switching from one behavior to the other. These experiments will provide an opportunity to learn or develop numerous techniques, including fluorescence microscopy, chronic extracellular electrophysiology, innovative procedures for surgery and behavioral analysis, as well as to continue and expand collaborative arrangements wiht productive scientists elsewhere. In addition to contributing toward a basic understanding of how the nervous system coordinates sensory information into precise physiological behavioral controls, this research has direct relevance to the etiology of specific behavioral pathology, such as dietary obesity, bulemia, and anorexia nervosa.
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0.966 |
1988 |
Norgren, Ralph |
F06Activity Code Description: Undocumented code - click on the grant title for more information. |
Sensory Mechanisms of Sodium Appetite @ Pennsylvania State Univ Hershey Med Ctr |
0.966 |
1989 — 1993 |
Pritchard, Thomas [⬀] Norgren, Ralph |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Cortical Integration of Taste and Smell Activity @ Pennsylvania State Univ University Park
Separate neurophysiological experiments have shown that neurons responsive to taste and smell stimulation are coextensive within a circumscribed area of the orbitofrontal cortex. Other experiments have shown that this area receives substantial projections from established gustatory and olfactory areas of the brain. Because these previous neurophysiological studies did not test both gustatory and olfactory stimuli, it is not known whether functional integration of taste and smell occurs in the orbitofrontal cortex. This project will use electrophysiological and anatomical techniques to address the following issues: (1) Do the chemosensory neurons in the orbitofrontal cortex comprise a single convergent population, a mosaic of independent olfactory and gustatory elements, or two contiguous, but functionally distinct areas, and (2) Which areas of the brain project to the chemosensory area(s) within the orbitofrontal cortex? These experiments will contribute important information about the functional organization of orbitofrontal cortex, an area of the forebrain that may be relevant to certain pathological types of ingestive behavior (e.g. anorexia nervosa and bulimia) that require cortical involvement.
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1 |
1995 — 1996 |
Norgren, Ralph |
F06Activity Code Description: Undocumented code - click on the grant title for more information. |
Parabrachial Taste Influence On the Ventral Forebrain @ Pennsylvania State Univ Hershey Med Ctr |
0.966 |
1995 — 2000 |
Pritchard, Thomas [⬀] Norgren, Ralph Reilly, Stephen |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
The Hierarchical Basis of Taste Perception. @ Pennsylvania State Univ University Park
9413025 Pritchard Taste is a critical sense for animal survival, determining what is good and what is not good to eat. Yet compared with our understanding of other sensory modalities like sight and hearing , we have only a rudimentary knowledge of the gustatory system. Sight, hearing and touch are centrally organized in a hierarchical fashion in the mammalian brain; in particular, the thalamus is a major brain region above the brainstem which processes and integrates sensory information before it gets to the level of the cortex. We have little comparable information on central processing in taste pathways. This project uses novel experiments with sophisticated behavioral tests to see what particular processing occurs in the brainstem, without the contributions from the thalamus. The unique approach will determine whether specific taste deficits represent a sensory loss, a change in behavioral motivation, or a perceptual deficit, each of which could influence taste- guided behavior. These results will provide needed fundamental advances in our understanding of taste; results will be important beyond chemosensory neuroscience, to cognitive and perceptual issues of brain function, and to the food industry.
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1 |
1997 — 2000 |
Norgren, Ralph |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Sensory and Hormonal Control of Salt Appetite @ University of Pennsylvania
Investigations of gustatory processing during salt appetite will focus on two hypotheses. The first hypothesis is that the sensory neural code for taste is altered in a manner that makes oral sodium more salient to the animal. The second hypothesis places the mechanism for the changed avidity in the ventral forebrain, beyond the central gustatory system, within the neural systems that are altered by the hormones controlling fluid balance. The first hypothesis requires behavioral and electrophysiological experiments. Na-appetite can be elicited with variety of procedures, all of which result in increased salt intake. What is not clear is whether a similar change in salt intake reflects the same alterations in the hedonic response to the sodium ion. We plan to use two short term measures, the taste reactivity test and lick pattern analysis, to determine whether the behavioral responses to taste during sodium hunger differ as a function of the method used to raise the appetite. These behavioral experiments were prompted, in part, by electrophysiological data demonstrating that dietary sodium deprivation reduces while diuretics increase central gustatory neural response to NaCl. These data suggest that different procedures for eliciting an appetite produce different perceptual alterations to sapid sodium. Further analysis of these phenomena both on the periphery and further centrally in the parabrachial nuclei (PBN) is dictated. Bilateral lesions of the PBN eliminate the expression of sodium appetite in naive rats, but similar lesions either in the nucleus of the solitary tract or the thalamic gustatory relay do not. Gustatory neurons in the PBN project not only to thalamus, but also to the ventral forebrain. Given the results from the lesion studies, the gustatory projections from the pons to the ventral forebrain take on added significance. Studies of the second hypothesis will focus on neurons within the septo-preoptic continuum that respond selectively to iontophoretically applied angiotensin. The number of such neurons and the magnitude of their responses increases in animals that have been pretreated with DOCA. In fact, the spontaneous activity of the entire region is enhanced by DOCA. During the next project period, a substantial effort will be devoted to examining the range and mechanisms of this steroid effect. Separate observations have demonstrated that, at some locations, minute doses of angiotensin applied iontophoretically can raise blood pressure and even elicit drinking behavior. We also will determine whether PBN influence on neurons in the area can be altered selectively with DOCA pretreatment.
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0.991 |
2002 — 2012 |
Norgren, Ralph |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Gustatory Control of Sodium Appetite @ Pennsylvania State Univ Hershey Med Ctr
DESCRIPTION (provided by applicant): Reward remains a central puzzle of neuroscience. Understanding its neural bases is key in developing rationale therapies for a broad spectrum of maladies such as drug addiction, obesity, anorexia nervosa, and depression. Salt appetite is a biological drive triggered by a negative body sodium balance that offers a unique model for investigating the central mechanisms of reward. Sodium appetite fulfills all of the criteria for motivation, as do hunger and thirst, but has some distinct advantages. Its adequate stimulus is simple, the sodium ion, and in the external environment, this stimulus is transduced by a single sensory system, taste. In most mammals, including humans, recognition of sodium is innate. Under normal circumstances, animals show at best a mild preference for weak saline solutions and actively avoid strong ones. When a Na-appetite arises, however, even strong salt becomes highly preferred. The question here is how a modest shift in body sodium balance brings about a dramatic increase in the reward value of this sapid stimulus? Unlike vision, audition, and somethesis, taste has direct neural connections with the limbic forebrain, a large system that is critical to the elaboration of motivation and reward. The overall premise is that gustatory afferent activity from the second central gustatory relay, pontine parabrachial nucleus (PBN), reaches neural reward systems via these limbic connections and, during sodium need, transforms the sensory message elicited by NaCl from aversive to rewarding. We already know that lesions of the PBN prevent the expression of Na-appetite, but that damage to the thalamic and cortical gustatory areas does not. We use the release of dopamine (DA) in the nucleus accumbens as a forebrain index of reward. Sham licking sucrose produces a substantial efflux of accumbens DA even in experienced animals. Under normal circumstances, sham intake of 0.15 M NaCl produces only a small DA spike. During Na-appetite, however, salt intake releases an accumbens DA plume rivaling that of sucrose. Based on these facts, we propose three experimental challenges to the overall premise. Specifically, we will use (1) central lesions, (2) microdialysis, and (3) FOS immunohistochemistry to determine if parabrachial gustatory neural activity distributed via the limbic forebrain is necessary and sufficient for the expression of a Na-appetite, and if these same pathways are responsible for modulating the release of accumbens dopamine during the appetite. The specific limbic areas to be tested include the lateral hypothalamus, the amygdala, and the bed nucleus of the stria terminalis. Pleasure is a product of brain activity. Understanding the neural bases of pleasure or reward is key in developing rational therapies for in broad spectrum of maladies such as drug addiction, obesity, anorexia nervosa, and depression. This project investigates the neural bases of reward using the sense of taste because some gustatory stimuli are inherently rewarding or aversive. The research goal is to determine how taste neural activity reaches brain areas that produce reward and how this sensory information is transformed in the process.
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1 |
2007 — 2010 |
Norgren, Ralph |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Neural Mechansims of Oil Reward @ Pennsylvania State University
DESCRIPTION (provided by applicant): Fat is a critical, highly preferred macronutrient and one of the major contributing factors to the current obesity epidemic. Although reducing the percentage of fat in the American diet is a high priority, this effort has been hindered by our poor understanding of fats sensory and rewarding properties. An appreciation for the central basis of oil reward awaits a better understanding of the sensory basis of fat and oil perception. Detection, discrimination, and even the appeal of fats and oils have been presumed to be within the purview of the somatosensory system, but the recent finding that fatty acids activate taste receptor cells suggests that the gustatory system plays a role as well. The experiments of Aim 1 will examine the ability of oils and oil/water emulsions to stimulate individual tactile, taste, and thermal fibers of the gustatory and somatosensory nerves that innervate the tongue. Specific Aims 2 and 3 will identify the forebrain structures that mediate the hedonic value of oil. The experiments of Aim 2 will combine measurements of dopamine release within nucleus accumbens with central gustatory and trigeminal lesions to identify the central pathways involved in oil reward. The experiments of Aim 3 will use a functional dependent variable, c-Fos, to identify additional pathways and nuclei involved with oil reward. The proposed experiments are innovative because the sensorineural and rewarding properties of oil have never been investigated. This research is important because fats and oils represent a significant and increasing percentage of the American diet. In order to curtail our appetite for high fat foods, we must understand how fats and oils are detected by the orosensory apparatus and how this sensorineural information is used by the brain to determine the nature of oil reward. Resolution of these issues will permit us and other investigators in the fields of taste and nutrition to examine the effect of dietary fat and oil on brain areas involved with appetite and satiety.
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1 |