The National Institutes of Health has awarded $2.2 million to researchers at the George Washington University (GW) School of Medicine and Health Sciences for a study on chronic stress. The project will investigate the changes that occur in the ventral tegmental area (VTA) of the brain, where dopamine neurons are located, during chronic stress.
Chronic stress is a common contributor to illnesses like depression and anxiety disorders. GABAergic neurons - those that produce gamma-Aminobutyric acid - make up 35% of neurons in the VTA. They are critical regulators of dopamine neurons and are robustly activated by acute stress. Previous research has observed what happens as a result of stress, but little is understood regarding what happens during stress.
We currently don't know what happens to the reward circuitry during chronic stress. Understanding those changes is important for furthering our understanding of how stress can have effects like loss of motivation."
Abigail Polter, Ph.D., Assistant Professor of Pharmacology and Physiology, GW School of Medicine and Health Sciences
Polter believes that chronic stress leads to persistent hyperactivity of VTA GABA neurons and this facilitates the emergence of maladaptive behavioral responses. Through the study, she expects to find that over the course of stress, the GABA neurons become more active and that activity is solidified by changes in synaptic plasticity.
Over the course of the study, Polter and her team will examine the dynamics of inhibition of VTA dopamine neurons by VTA GABA neurons during stress. They will investigate how activity and strength of synaptic inputs onto VTA GABA neurons change during stress. Also, the team will examine whether in vivo activity of VTA GABA neurons contributes to individual differences in the emergence of disinterest in social contact post-stress.
The study will take a multidisciplinary approach utilizing electrophysiology, optogenetics, behavior, and fiber photometry to address the hypothesis. The project will also make use of GW's Nanofabrication and Imaging Core facility, which integrates cutting-edge instrumentation and customized support services for imaging, elemental analysis, materials characterization, measurement and fabrication.
"We hope that this work can ultimately contribute to the search for novel treatments for depression or even prophylactic treatments one could take if they were undergoing a stressful event," Polter said. "Something like that could be used during a stressful occurrence to reduce the risk of later developing depression."