Neuronal Regulation of impulsivity and metabolic adaptation
Hatter, Jessica, Pharmacology - School of Medicine, University of Virginia
Scott, Michael, MD-PHAR Pharmacology, University of Virginia
Dysfunction and the resulting behavioral aberrations are highly associated with the development of over 200 types of mental disorders. Thus, increased understanding of the cognitive causes of psychopathologies is important for directing pharmacologic interventions. To further explore how disparate systems affect behavior, we conducted studies exploring cortical control of behavior and transcriptomic studies of a subset of neurons in the hindbrain that are highly implicated in the control of feeding and response to metabolic adaptation.
While dysfunction of the PFC is highly correlated with mental disorders and the development of addiction, little is known about how alterations in neuron activity can drive changes in behavior. To query how the cortical microcircuit functions during specific behavioral tasks, I harnessed a method of specific caspase-3-mediated ablation to explore how it modulated behavior. Using this animal model, I revealed a novel circuit-level mechanism in which a subtype of cortical interneuron functions as a gate to modulate behavior during periods of high expectation.
Glucagon-like peptide-1 (GLP-1) is believed to be the most potent effector of gut-hindbrain communication and is implicated in appetite suppression and feeding behavior. GLP-1 agonists have been pharmacologically relevant in the treatment of type 2 diabetes and induce weight loss in obese individuals. Previous research found that activation of GLP-1 neurons in the hindbrain reduced food intake in both lean and obese, but selectively mediated weight loss only in obese animals. To query how obesity may influence neuronal action, we conducted transcriptomic profiling in GLP-1 neurons from the hindbrain in lean and obese animals.
PHD (Doctor of Philosophy)