New anti-diabetes and obesity GLP1R agonists medications (e.g., Wegovy and Ozempic) work incredibly well at treating these conditions, but deal with aversive side-effects (including nausea, vomiting, and diarrhea) that lead to reduced adherence and cessation of treatment. Understanding the neuron populations and circuits that control these aversive responses will allow for the development of safer and more effective therapeutics.
The dorsal vagal complex in the hindbrain is uniquely positioned to receive and integrate aversive stimuli. Sequencing of the dorsal vagal complex by the Myers’ lab and collaborators identified two neuron populations within the nucleus of the solitary tract (NTS), Vglut3- and Rxfp1-expressing neurons, that we hypothesize control the aversive response but not the long-term food intake suppression response to GLP1R agonists. My project will use chemogenetic activation and tetanus toxin silencing of NTS Vglut3 and Rxfp1 neurons with subsequent food intake and conditioned aversive response studies to identify their role in satiation and aversive response.