Caroline Geisler, PhD

Central Mechanisms of Amylin Mediated Attenuation of Motivated Feeding

Caroline received her Ph.D. in Animal Sciences from the University of Arizona. Under Dr. Ben Renquist, Caroline’s graduate work centered on understanding how hepatic lipid accumulation induced changes in hepatic metabolism drive dysregulations in systemic insulin homeostasis. In the Hayes’ lab, Caroline’s focus has shifted to the neurohormonal control of energy homeostasis. The amylin signaling system is an attractive therapeutic target to treat obesity as amylin acts synergistically with other satiation signals to decrease food intake and enhance weight loss. This work is investigating how amylin signaling in the ventral tegmental area (VTA) engages a neural network to the prefrontal cortex (PFC) to invoke satiation and limit motivated feeding especially of highly palatable and rewarding foods.

Our results demonstrate that intra-VTA amylin decreases food-evoked phasic dopamine release in the mPFC, and attenuates food-directed impulsive behavior. Surprisingly, amylin receptor expression is not observed on VTA-to-mPFC projecting neurons but is found on GABAergic neurons in the VTA that provide monosynaptic inputs to this pathway. Blocking intra-VTA GABA signaling diminishes the anorectic response to intra-VTA amylin. These results indicate that VTA amylin signaling stimulates GABA-mediated inhibition of dopaminergic projections to the mPFC to mitigate impulsive consumption of palatable foods.

The other focus of Caroline’s work in the Hayes’ lab is to understand how the glial-released satiation hormone octadecaneuropeptide (ODN) regulates energy homeostasis, central glucose sensing, and brain barrier transport.