Gustatory coding in brainstem nuclei using a novel c-Fos-tau-LacZ mouse model

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Project Summary Obesity is a major health issue with approximately two thirds of the U.S. population considered overweight and a third of those classified as obese. Overconsumption of high calorie foods contributes significantly to the development of obesity. Thus, identification of factors that influence food choice is important for the development of effective obesity treatments. In this regard, the sense of taste has a direct impact on food preference. Therefore, the neural pathways involved in how the brain represents taste can contribute to our understanding of the etiology of obesity. One of the most effective and widely-used methods to determine the neural substrate that underlies sensation of taste is visualization of the spatial patterns of expression of the activity-dependent marker, c-Fos. Recently, the Fos-tau-LacZ transgenic mouse line was developed in which activation of the c-Fos gene results in expression of tau-linked Beta-galactosidase (Beta-gal) in the cytoplasm of activated cells; thereby enabling the examination of the morphology of c-Fos positive cells. Furthermore, the perdurance of Beta-gal in these transgenic mice is much longer than c-Fos protein itself; Beta-gal can be seen up to 24 hours post stimulation in the brainstem, whereas c-Fos protein lasts 1-3 hours and c-Fos mRNA peaks 30 min. post stimulation. This difference in timing between Beta-gal and mRNA purdurance enables visualization of c-Fos expression in response to two stimuli, separated temporally, within the same animal (e.g. Beta-gal) expression and c-Fos mRNA expression). Accordingly, I can assess whether individual cells respond to multiple taste stimuli. The current proposal will use Fos-tau-LacZ transgenic mice to quantify morphological and spatial differences in cellular activation (e.g. Beta-gal expression and c-Fos mRNA) in brainstem taste nuclei in response to stimuli of different modalities (sweet, ¿umami¿/savory and bitter) and different taste hedonics (appetitive vs. aversive). Moreover, the proposal will also assess changes in this central taste representation following loss of sweet- and umami- specific sensory input via deletion of the T1R3 receptor- an obligatory subunit for the detection of these qualities. The data obtained from this proposal will provide valuable insight into the spatial and morphological organization of taste representation within the nucleus of the solitary tract.