Alhadeff Lab Projects
Body-Brain communication and feeding behavior
Energy balance involves exquisite coordination between our peripheral senses and the brain. Our sensory systems allows us to perceive both the external environment and sensations within our body. Our lab’s work has demonstrated the striking ability of oral and gut signaling to rapidly change in vivo brain activity. What are the neural pathways through which oral and gut signals influence the brain? How do these signals change activity across neural networks and how do these changes impact feeding behavior? Answers to these questions will provide a better understanding of how our internal senses communicate with the brain to control energy balance.
Interactions between central homeostatic and reward systems
In humans and rodents alike, we eat not just for survival but also because eating is pleasurable. And in the brain, we know that both homeostatic and reward circuits are engaged during food seeking and consumption. Historically, these systems were thought to drive discrete aspects of ingestive behavior: hypothalamic circuits control energy homeostasis, while midbrain reward circuitry influences hedonic food intake. Our recent findings, however, suggest that these systems actually work together to influence behavior. We discovered a bidirectional, interdependent relationship between hypothalamic “hunger” neurons and midbrain dopamine circuits. How do these neural systems interact to drive motivated behavior? Understanding this neural interaction will provide insight into both eating and substance abuse disorders.
“Hunger is the best sauce; for it makes all food palatable, and costs nothing.”
Mechanisms of action for GLP-1r agonist drugs
Glucagon-like peptide-1 receptor (GLP-1R) agonists (e.g. Ozempic/Wegovy) have exploded in popularity for the treatment of diabetes and obesity because of their outstanding ability to regulate blood glucose and reduce body weight. Beyond these indications, recent data suggest they may also be candidates for the treatment of other disorders (e.g. substance use disorders, inflammation, neurodegenerative diseases, coronary artery disease, and more). However, GLP-1R agonists also have several side effects (e.g. nausea, vomiting) that can limit treatment efficacy and quality of life. We are interested in understanding the mechanisms and functions of GLP-1R expressed across different brain regions and tissues to understand their full breadth of potential use and potentially mitigate their associated side effects.