The PI will determine the relative contributions made by food palatability and caloric content, to neural activity underlying food reward. The obesity epidemic is due, in part, to unchecked consumption of highly palatable, densely caloric foods. The nucleus accumbens and dopamine signaling within this region are associated with food reward. Indeed, they are critical components of the circuitry that underlies behavior directed at obtaining and consuming rewards. However, most attempts to determine physiological correlates of food reward con- found palatability and caloric value. This study will determine whether physiological correlates of food reward are dependent on the presence of calories or the positive hedonic aspects of taste stimuli.
The aims will be achieved by delivering intraoral infusions of sweet solutions and varying the caloric load associated with them.
For Aims 1 and 2, sucrose will be compared to the non-caloric sweetener saccharin.
In Aim 3, intragastric infu- sions of nutrient will be paired with intraoral infusions of flavored saccharin. In all cases, physiological responses are measured in nucleus accumbens: fast-scan cyclic voltammetry will be used to measure phasic fluctuations in dopamine and multi-wire electrophysiology will be used to monitor firing of individual neurons. All techniques are to be employed in awake, behaving rats and are novel technical approaches for the PI. Training will take place at University of Illinois at Chicago (UIC) in the laboratory of Dr. Mitchell Roitman (and for Aim 3, a Yale University in the laboratory of Dr. Ivan de Araujo). Dr. Roitman has extensive experience with the recording techniques as well as the necessary conceptual and theoretical background. Dr. de Araujo will teach the PI to perform intragastric cannulations, which the PI will integrate with voltammetry recordings. This novel combination will set his research path distinct from his mentor and others in the field. Additionally, an Advisory Committee has been established comprising Dr. Roitman, Dr. Simon Alford (co-mentor) and Dr. Marina Wolf (consultant). Drs. Alford and Wolf have excellent track records of advancing trainees to independence. Further- more, their laboratories and resources, specializing in in vitro techniques, will be available for the collection of data for an R01 application to be submitted during this award. Technical and conceptual training will be augmented by didactic workshops, seminars and conferences. Through UIC's Center for Clinical and Translational Studies the PI will gain further appreciation for the nature of clinical disorders of motivation (obesity, drug ad- diction) as well as current treatment and prevention strategies. Industry workshops will provide the very latest developments for the new technical approaches proposed. Academic conferences will keep the PI up-to-date with how technical advances are being employed and provide feedback from the community. Coupled with his previous training, the plan described herein will prepare the PI to establish a fully independent research pro- gram working to determine the biological bases for adaptive (e.g. feeding) and maladaptive (e.g. drug taking) behaviors using multiple levels of analysis - from molecular/cellular to systems/behavioral.
The obesity epidemic poses a huge health challenge across the globe that is fueled, at least in part, by overconsumption of foods that are highly palatable and densely caloric, i.e. junk foods. Reward circuitry directs behavior towards consumption, and is a target for treatment and prevention, but it remains unclear if this is due to the hedonic or metabolic consequences of junk foods. This proposal will assay reward circuitry in real time to determine how palatability and caloric content drive neural activity and hence behavior directed at consumption.
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|Marinelli, M; McCutcheon, J E (2014) Heterogeneity of dopamine neuron activity across traits and states. Neuroscience 282:176-97|
|Cone, Jackson J; McCutcheon, James E; Roitman, Mitchell F (2014) Ghrelin acts as an interface between physiological state and phasic dopamine signaling. J Neurosci 34:4905-13|