Hedonic hotspot interactions for the generation of 'liking' and 'wanting'

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PROJECT SUMMARY: The primary role of this proposal is to investigate the corticolimbic circuitry that controls `liking' reactions to rewards, such as palatable sweet tastes. `Liking', `wanting', and learning are three distinct components of reward, with distinguishable brain mechanisms, which interact to guide motivated behavior.1,2 Most research on brain reward mechanisms has traditionally focused on learning and `wanting', because of the challenges in measuring `liking' in independent ways to identify its neural mechanisms. Yet, `liking' dysfunction are important components of neuropsychiatric disorders, including depression, and so its neurobiology is important to understand. One method that has successfully measured `liking' is the affective taste reactivity test, which measures affective orofacial expressions to various tastes, which are homologous across various species of animals, and which has identified underlying brain mechanisms.3–5 Studies using measures of affective `liking' reactions to taste have shown `liking' is controlled by a network of brain hedonic hotspots in corticolimbic sites including nucleus accumbens, ventral pallidum, orbitofrontal cortex, and insula.6–12 Research in our lab, including my own, has shown that optogenetically activating the hotspots can amplify `liking' reactions to the hedonic impact of palatable sucrose reward. 13–16 Activating a hedonic hotspot to amplify `liking' also recruits Fos expression in the other hedonic hotspots, suggesting they're all simultaneously recruited into action. 6,17 However, while these hedonic hotspots are thought to mutually recruit and interact to produce `liking' enhancements, the anatomical projections connecting them have not been identified, as direct projections between hotspots do not exist 18,19. The current proposal will investigate the indirect anatomical connections and functional recruitment and interactions within the hedonic hotspot circuitry that amplifies intense `liking' expressions for palatable rewards. First, the anatomical afferent and efferent projections of the hedonic hotspots in NAc, VP, insula, and OFC will be identified, using anterograde and retrograde mapping techniques to identify potential sites of convergence between OFC and NAc hotspots, and between NAc and VP hotspots. A novel high spatial resolution atlas brain mapping technique will be used in order to standardize connectivity patterns onto the Swanson rat brain atlas.20–22 The hypothesis that unanimous recruitment of the hedonic hotspots is necessary for `liking' enhancement will also be tested by activating one hedonic hotspot and simultaneously disrupting another during taste `liking' reactions. Results from these experiments will provide insights into the functional circuitry that mediates reward `liking' that may contribute to understanding various neuropsychiatric disorders. Through the proposed training, I will learn new techniques, including neuroanatomical projection mapping, brain atlas plane of section analysis, advanced immunohistochemistry, and complex optogenetic neurobehavioral analyses. The NRSA predoctoral fellowship will help me transform into a successful, independent neuroscientist.