Our research focuses on the neural control of feeding and body weight, with a focus on the role that the mesocorticolimbic dopamine system plays in the regulation of feeding, metabolism, activity, and body weight. The mesocorticolimbic dopamine system is the primary neural circuit involved in motivated behavior toward pleasurable, rewarding substances. This includes the rewarding and pleasurable qualities of food, especially palatable high fat and high sugar foods (e.g. food reward). In addition to playing an important role in controlling reward-related food intake, dopamine also plays a role in homeostatic feeding, or the baseline feeding required to maintain normal physiological function. We use a diverse array of approaches at the molecular, cellular, circuit and behavioral level to address multiple important questions related to this broader topic. This includes new and cutting-edge techniques (optogenetics, chemogenetics, genetic disruption with the CRISPR/Cas9 system, fiber photometry, etc) as well as more standard, classic approaches (patch-clamp electrophysiology, immunohistochemistry, etc).
Overall, our research centers around two related major questions: 1-How do dopamine circuits control feeding, activity, metabolism, and body weight? and 2-How do alterations in feeding and body weight (e.g. obesity, food restriction) alter the activity of dopamine circuits (which would then feed back onto question 1).
Specific projects ongoing in the laboratory at this time include the following:
1. Interactions of the melanocortin system with dopamine circuits in the regulation of feeding and energy homeostasis. The melanocortin system is centered in the hypothalamus, and has been widely studied for its role in the control of energy homeostasis. Our lab (and others) has shown that the melanocortin system can interact with the mesolimbic dopamine system to regulate feeding and body weight.
1a. Analysis of VTA MC3R neurons. Neurons expressing the melanocortin-3 receptor (MC3R) in the VTA are the likely site for the actions of the melanocortin system. Thus, we are studying the role that these neurons play in the regulation of feeding and body weight. This includes testing: a-whether altering the activity of these neurons regulates feeding and body weight using a number of different feeding paradigms; b-where these neurons project and where their inputs arise; and c-which neurotransmitters these neurons release.
1b. Analysis of MC3Rs in the VTA and MC3R/MC4R signaling in vivo. We are testing whether knocking out MC3Rs in the VTA alters feeding and body weight under different conditions. We are also studying how MC3Rs and MC4Rs signal and are regulated in native neurons.
2. What are the alterations in Dopamine neurons and circuits following changes in feeding and body weight. This includes testing a-how dopamine release is altered with the development of obesity and following food restriction (i.e. dieting); b-whether there are structural alterations in VTA dopamine neurons with obesity and food restriction; and c-whether there are changes in intrinsic activity or the activity of afferent inputs following obesity or food restriction.
We also have some other smaller ongoing projects in the lab as well.
3. How do drugs of abuse decrease feeding? This includes testing whether common drugs that decrease feeding (amphetamine, cocaine, nicotine) affect different aspects of feeding (homeostatic feeding, food reward) similary and whether these drugs affect feeding similarly in males and females.