The biological function of sweet taste perception is to facilitate the detection of carbohydrate sources and trigger ingestive behavior. However, very little is known about how the neural circuitry that commands feeding senses the presence of nutrients in sweet substances.
The aim of the studies outlined in this proposal is to start filling such fundamental gaps in our knowledge. Our investigations aim at providing a comprehensive functional circuit analysis of sweet taste activation of the basal ganglia - the major sensorimotor relay of the brain. We will specifically aim at identifying the basal ganglia circuits that sense te presence of nutrients in sweet substances. This will further our understanding of how sweet taste perception can modify the behavioral repertoire of an organism. Using the mouse as our model organism, we will employ a multidisciplinary approach that combines behavioral, neurochemical, electrophysiological, optogenetic, chemogenetic, and virus-based neuroanatomical tracing techniques. Accordingly, our Specific Aims are:
Specific Aim 1 : To characterize how basal ganglia circuits respond to sweet chemosensory signals Specific Aim 2: To generate a functional map of the circuits engendering behavioral responses to sweet chemosensory signals Specific Aim 3: To use molecular tracing techniques to identify the downstream targets of basal ganglia subcircuits mediating behavioral responses to nutritive sweet chemosensory signals.
The behavioral implications of chronically consuming non-nutritive 'artificial' sweeteners have been the focus of much controversy. Particularly contentious is the notion that non-nutritive sweeteners favor weight gain by producing a perceptual mismatch between intense sweetness and the absence of ensuing metabolic cues. Our inability to address such important questions exposes our lack of understanding on how neural circuits encode the presence of calories in sweet substances. The aim of the studies outlined in this proposal is to fill this fundamental gap in knowledge.
|Han, Wenfei; Tellez, Luis A; Perkins, Matthew H et al. (2018) A Neural Circuit for Gut-Induced Reward. Cell 175:665-678.e23|
|Han, Wenfei; Tellez, Luis A; Rangel Jr, Miguel J et al. (2017) Integrated Control of Predatory Hunting by the Central Nucleus of the Amygdala. Cell 168:311-324.e18|
|de Araujo, Ivan E (2016) Circuit organization of sugar reinforcement. Physiol Behav 164:473-477|
|Tellez, Luis A; Han, Wenfei; Zhang, Xiaobing et al. (2016) Separate circuitries encode the hedonic and nutritional values of sugar. Nat Neurosci 19:465-70|
|Han, Wenfei; Tellez, Luis A; Niu, Jingjing et al. (2016) Striatal Dopamine Links Gastrointestinal Rerouting to Altered Sweet Appetite. Cell Metab 23:103-12|