2002 — 2004 |
Boughter, John D |
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. |
Bitter Taste: Physiology and Behavior @ University of Maryland Baltimore
DESCRIPTION (provided by applicant): Considerable variation exists among inbred strains of mice in their behavior toward bitter-tasting compounds. These differences have been demonstrated almost exclusively using long-term (24- or 48-hour) intake tests. Such natural variation in behavior has fostered physiological, biochemical, and molecular research aimed at elucidating taste transduction events and the identity of genes underlying the mechanisms of bitter taste. Two inbred strains exist that differ substantially in their intake of bitter stimuli: SWR/J (SW: bitter sensitive) and C3HeB/FeJ (C3: bitter insensitive). An understanding of how these strains differ physiologically could provide information useful for developing models of bitter taste function. However, very little is known about the responsiveness of taste receptor cells of these strains to bitter stimuli. Further, it is not certain that the long- term intake tests used to contrast these strains provide uncontaminated indicators of gustatory function. The approach taken in this application is to combine refined behavioral procedures with electrophysiological studies of taste receptor cells to elucidate the physiological bases of these behavioral differences. Behavioral measures from mice from both strains will be acquired using a short-term test designed to minimize non-taste (e.g., post-ingestive) factors. Precise concentration-response functions acquired in this way will provide a clear indication of the behavioral differences among bitter stimuli for these strains, based on taste cues. In electrophysiological experiments, taste receptor cells from the tongue and palate of these mice will be investigated using whole-cell-recording methods in an intact epithelial preparation. Cells will be tested with an array of bitter stimuli to test the hypothesis that the behavioral differences between strains are due to: 1) a greater number of cells responding to bitter stimuli in the bitter-sensitive SW strain; or 2) an altered concentration-response function for bitter stimuli in the bitter-insensitive C3 strain. By examining these strain differences in receptor cell function, these studies should help to link ongoing molecular advances to the neural mechanisms underlying bitter taste function.
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0.988 |
2006 — 2014 |
Boughter, John D |
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. |
Sensory Coding in Taste @ University of Tennessee Health Sci Ctr
DESCRIPTION (provided by applicant): Ingestive decisions play a key role in a number of human conditions including obesity, diabetes, anorexia, hypertension, and coronary artery disease. The sense of taste is the most important factor in regulating these ingestive decisions, and therefore plays an important role in human health. Research conducted over the last few decades shows that taste centers in the brain have direct reciprocal connections with brain areas involved in homeostasis and ingestion. Taste has also been shown to engage the reward system, and dysfunction in this system may lead to overeating and obesity. However, the exact route whereby taste information engages reward and ingestive brain areas is unclear. The parabrachial nucleus (PBN) is a critical relay in the brainstem where gustatory information diverges via several ascending pathways to access forebrain sites involved in sensory discrimination, learning, intake and visceral processing, as well as reward. The studies of this proposal will test the hypotheses that a projection from the PBN to the ventral tegmental area (VTA) mediates taste-evoked reward, and a projection from the PBN to the lateral hypothalamus (LH) mediates taste-evoked ingestion. We will use a combination of complementary anatomical, physiological, and behavioral techniques to address this hypothesis. We propose the following specific aims: Aim 1: Functional organization of the gustatory PBN in mice. We will collect comprehensive normative data establish the organization of this key nucleus in wild type and taste-impaired mice. Aim 2: Does a direct projection from the PBN to the VTA mediate taste-evoked reward? This hypothesis will be first be evaluated with tract tracing and taste-evoked fos-like immunoreactivity (FLI) techniques: We will investigate whether or not VTA-projecting neurons are activated preferentially by sweet-tasting, rewarding stimuli in intact or taste-blind mice. We will also physiologically characterizing taste neurons that project to VTA using in vivo recording techniques. Finally, we will test the hypothesis that the VTA is essential for normal reward, but not taste function, by combining lesions of this area with behavioral analysis. In Aim 3, we will use a similar set of approaches to address the hypothesis that a direct projection from the PBN to the LH mediates taste-evoked ingestion, including tract tracing and taste-evoked FLI, in vivo physiology, and lesions of LH followed by measurement of behavior. We will utilize taste-blind trpm5 null mice in these experiments in order to separate effects of taste vs. post-ingestive feedback. PUBLIC HEALTH RELEVANCE: Ingestive decisions play a key role in a number of human conditions including obesity, diabetes, anorexia, hypertension, and coronary artery disease. The sense of taste is the most important factor in regulating these ingestive decisions, and therefore plays an important role in human health. The goal of this research is to elucidate pathways in the brain that link taste to feeding and reward.
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0.988 |
2007 — 2008 |
Boughter, John D |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Genetic Dissection of a Motor Central Pattern Generator @ University of Tennessee Health Sci Ctr
[unreadable] DESCRIPTION (provided by applicant): Central pattern generators (CPGs) are rhythmically active neural networks that underlie many stereotyped and repetitive voluntary muscle movements such as whisking or fluid licking. Fluid licking in rodents is an example of a promising, simple model of a CPG: It is a highly stereotyped behavior characterized by rhythmic tongue and jaw movements, and it is thought to be controlled by a neural substrate distributed in the medullary reticular formation in the brainstem. In preliminary observations, we have demonstrated that mice are a superb species choice for investigating the genetic basis of the licking CPG - the common inbred strains C57BL/6J (B6) and DBA/2J (D2) have a robust, non-overlapping phenotypic difference in lick rate. The identification of genes underlying differences in lick rate should have a huge payout for the study of CPGs. Mice can then created with gene-targeted deletions or insertions, allowing for specific physiological or anatomical investigation. We propose to take advantage of a newly augmented resource for our genetic dissection of licking: The BXD advanced recombinant inbred (Rl) strain set. These mice will allow for precision genetic mapping of quantitative trait loci (QTL) that underlie behavioral traits. We propose to use a novel high-throughput assay for lick rate to test a set of -80 BXD Rl strains, and map quantitative trait loci (QTLs) with high precision that underlie strain variation in lick rate. Relevance: Complex animals such as humans possess a number of motor responses that are stereotypic and/or repetitive in nature. Comparison of the genes and mechanisms underlying stereotyped repetitive movements versus plastic behaviors will be a source of information relevant for a number of human CMS disorders involving abnormal repetitive movements. [unreadable] [unreadable] [unreadable]
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0.988 |
2016 — 2017 |
Boughter, John D Fletcher, Max L (co-PI) [⬀] |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Taste Responses in Defined Cell Types in Gustatory Cortex @ University of Tennessee Health Sci Ctr
? DESCRIPTION (provided by applicant): Ingestive decisions play a key role in a number of human conditions including obesity, diabetes, anorexia, hypertension, and coronary artery disease. One of the most important factors regulating these decisions is the sense of taste. The gustatory cortex in mammals has been shown to be involved in taste learning and behavior, and electrophysiological studies have shown that taste-activated neurons in this area tend to be broadly tuned (with regard to taste quality), multi-modal, and modulated by behavioral state. However, it is not clear how taste quality itself is encoded in the GC, and whether stimulus tuning in individual neurons varies as a function of cell type or functional connection. Two-photon (2P) imaging is a technique that allows for the simultaneous recording of taste-evoked responses in a large numbers of neurons in vivo. However, only a couple of 2P studies in the taste system have been published to date. We will combine 2P imaging with specific identification of cell types, accomplished by either Cre-dependent expression or retrograde labeling. Collectively, these experiments will test the hypothesis that taste sensitivities and tuning profile vary in GC neurons as a function of cortical depth, cell type (pyramidal cell vs. interneuron) or projection pattern. Aim 1 will investigate compare taste responses in Thy1-expressing pyramidal cells and Calretinin-expressing interneurons to the greater population of all labeled cells in GC. Aim 2 will investigate taste responses in GC neurons retrogradely labeled from either gustatory thalamus or basolateral amygdala.
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0.988 |
2018 — 2021 |
Boughter, John D Fletcher, Max L (co-PI) [⬀] |
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. |
Spatial Taste Coding in Mouse Gustatory Cortex @ University of Tennessee Health Sci Ctr
Project Summary Ingestive decisions play a key role in a number of human conditions including obesity, diabetes, anorexia, hypertension, and coronary artery disease. One of the most important factors regulating these decisions is the sense of taste. The gustatory cortex (GC) in mammals has been shown to be involved in taste learning and behavior, and electrophysiological and imaging studies suggest taste quality information is encoded in the activity of both specific and broadly responsive taste-activated neurons. However, it is not clear how taste quality is spatially organized across this brain area. We will use two-photon (2P) imaging to systematically map taste quality across the breadth of GC, evaluating the hypothesis that it has an overlapping organization, with likely overrepresentation of particular tastes at the anterior and posterior extremes. We will also combine 2P imaging with specific identification of cell types, accomplished by either Cre-dependent expression or retrograde labeling. Finally we will evaluate taste responses in GC following taste learning. Collectively, these experiments will shed light on how tastes are organized in this key brain area at a cellular level, and how they are modified with behavior. Aim 1 will systematically map taste responses along the anterior-posterior axis, and also with respect to dorsal-ventral location and depth. Aim 2 will compare taste responses in Thy1- expressing pyramidal cells and GAD-expressing interneurons to the greater population of all labeled cells in GC. Taste responses will also be examined in cells that project to contralateral cortex, or to amygdala. Aim 3 will investigate taste responses in GC neurons following taste aversion learning and extinction.
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0.988 |