Christian H Lemon
Saint Louis University
Project start date: 2011-03-01
Project end date: 2016-02-29
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Grants awarded to Christian H Lemon
GUSTATORY NEURAL CODING IN MICE: CONNECTING TASTE RECEPTORS TO THE BRAIN
Christian H Lemon
Saint Louis University, Saint Louis, Mo 63103
Grant 7R03DC008194-04 from National Institute On Deafness And Other Communication Disorders
Abstract: Molecular studies have recently identified two families of taste receptors. The T1r receptors recognize some sweet or amino acid stimuli, whereas T2r receptors are implicated for the detection of bitter-tasting ligands. The expression patterns of these receptors have invigorated interest in the idea that sweet and bitter taste are represent by dedicated coding channels in the nervous system; however, sweet- or bitter-responsive central gustatory neurons vary in their sensitivities to stimuli of other taste qualities, which questions whether input from T1r or T2r receptors is segregated to specifically-tuned cells in the brain. Experiments in this application involve electrophysiological measurement of taste responses in single neurons in the brain stem in mice with targeted manipulation of the gene Sac or Soa. Sac influences preference for sweets in mammals and encodes the sweet taste receptor T1r3. In Aim 1, we will measure differences in neural responding to sweet-tasting stimuli between mice engineered to carry a non-functional Sac allele (T1r3 knockout mice) and wild-type mice. Soa regulates sensitivity to bitter-tasting stimuli and co-localizes with the T2r bitter taste receptor genes. In Aim 2, neural responses to bitter-tasting stimuli will be compared between two strains of mice that genetically differ at only the gene Soa. These studies will identify categories of neurons in which taste responses to sweet or bitter stimuli are influenced by the manipulation of these genes, revealing cell types that receive input from the receptor products of Sac or Soa. The specificity of these identified cell types will be evaluated to determine if they could function as coding channels for the taste qualities of sweet or bitter or if their response properties are conducive to a different coding strategy. Results will bear on how taste information mediated by the receptors encoded by Sac and Soa is represented by neural activity. These experiments will test the hypothesis that genetic variation at Sac or Soa influences central gustatory neurons that are variably sensitive to stimuli of different taste qualities. Moreover, these experiments will identify categories of gustatory neurons in the brain that are fundamental to the neural substrates by which Sac and Soa influence behavioral responding towards taste stimuli, which will provide insight into the neurobiological mechanisms by which these genes control taste preference. Taste preferences guide dietary choices leading to many health problems in humans, such as cancer, obesity, and diabetes
Keywords: 10, 11-dimethoxystrychnine; Acids; Affect; Alleles; Allelomorphs; Amino Acids; Bears; Behavior; Brain; Brain Stem; Brainstem; Cancers; Categories; Cells; Central Nervous System; Cinchonan-9-ol, 6`-methoxy-, (8alpha, 9R)-; Code; Coding System; Detection; Diabetes Mellitus; Encephalon; Encephalons; Engineering; Engineerings; Epithelium; Family; G Protein-Complex Receptor; G-Protein-Coupled Receptors; Gene variant; Genes; Genetic; Genetic Diversity; Genetic Variation; Genomics; Gustation; Health; Human; Human, General; Inbred Strains Mice; Knock-out; Knockout; Knockout Mice; Knowledge; Label; Ligands; Link; Localized; Logic; Malignant Neoplasms; Malignant Tumor; Mammalia; Mammals; Mammals, General; Mammals, Mice; Man (Taxonomy); Man, Modern; Maps; Measurement; Measures; Mediating; Mice; Mice, Inbred Strains; Mice, Knock-out; Mice, Knockout; Molecular; Mouse Strains; Murine; Mus; NRVS-SYS; Nerve Cells; Nerve Unit; Nervous; Nervous System; Nervous System, Brain; Nervous System, CNS; Nervous system structure; Neural Cell; Neuraxis; Neurocyte; Neurologic Body System; Neurologic Organ System; Neurons; Null Mouse; Obesity; Paper; Pattern; Process; Property; Property, LOINC Axis 2; Proteins; Quinine; Receptor Gene; Receptor Protein; Saccharose; Salts; Son; Specificity; Stimulus; Strychnidin-10-one; Strychnidin-10-one, 2, 3-dimethoxy-; Strychnine; Sucrose; Sweeteners; Sweetening Agents; Taste; Taste Bud Cell; Taste Perception; Testing; To specify; Ursidae; Ursidae Family; Variant; Variation; Variation (Genetics); Wild Type Mouse; adiposity; allelic variant; alpha-D-Glucopyranoside, beta-D-fructofuranosyl; aminoacid; base; behavior influence; behavioral influence; brucine; cell type; congenic; corpulence; corpulency; corpulentia; diabetes; dimethoxystrychnine; experiment; experimental research; experimental study; gene product; genetic manipulation; insight; interest; malignancy; neoplasm/cancer; neural; neurobiological mechanism; neuronal; obese; obese people; obese person; obese population; preference; receptor; relating to nervous system; research study; response; sweet receptor; sweet taste; sweet taste perception
Project start date: 2006-04-01
Project end date: 2010-03-31
Budget start date: 1-JUL-2008
Budget end date: 31-MAR-2010
PFA/PA: PAR-04-062
7R03DC008194-04 (2008): $0
5R03DC008194-02 (2007): $70883
1R03DC008194-01 (2006): $73000