The Neural Organization of Taste Neophobia - Project Summary Neophobia is defined as a fearful reaction to novel stimuli or situations. When an animal encounters a novel food, they approach and consume it with cautiousness. For humans, this behavior has significant health consequences. Food Neophobia is especially prevalent in children, and the rejection of certain types of foods has serious consequences for the acute health of the child. Moreover, food Neophobia in childhood has long- lasting adverse effects on dietary choices associated with eating disorders, poor health outcomes, and disease. In rodents, taste Neophobia is an important behavioral reaction that ensures a minimized threat of toxicity in unfamiliar foods, including those that are inherently appetitive. When faced with a novel food or taste, animals consume a relatively small amount during the initial encounter. If this consumption yields no adverse consequences, a memory for a “safe” taste is formed, and animals will more readily increase their intake in subsequent test sessions, a process is known as attenuation of Neophobia. While lesions studies have begun to identify the brain regions involved in taste Neophobia and its attenuation, relatively little is known about the underlying circuits or the neural correlates of these behaviors. For example, there have been no attempts at exploring how Neophobia and attenuation impact neuronal responses in awake, behaving animals in key areas of the central taste pathway, including the gustatory cortex, gustatory thalamus, and nucleus basalis. The overall goal of this project is to understand this process by investigating how information regarding the novelty and familiarity of tastes are encoded within these circuits. Our central hypothesis is that Neophobia is driven by enhanced responses in both gustatory cortex and thalamus, and its attenuation is mediated by cholinergic activity from basal forebrain inputs. We will use calcium imaging of defined cholinergic and gustatory cell types combined with chemogenetic manipulation in awake animals during Neophobia and attenuation to test these hypotheses. The findings of these experiments will be significant in that they will be the first to explore neuronal activity in central taste regions during Neophobia and attenuation. Further, our findings will fundamentally advance our knowledge of how taste Neophobia is encoded in central taste circuits and the role of cholinergic input in this behavior. These findings will be important not only in increasing our understanding of this important form of taste learning but also in furthering our understanding of the basic mechanisms underlying novelty processing within sensory regions.