Fear is a powerful emotion and under normal conditions this works to the advantage of every species on this planet. One of the most poignant examples of this is post-traumatic stress disorder (PTSD). This project maps the neural circuit underlying the extinction of PTSD by combining molecular genetic tools with in depth behavioral analyses. Using a rodent model of PTSD adapted for use in the mouse, it extinguishes specific symptoms of PTSD such as enhanced fear, increased aggression and disruptions in sexual behavior, by genetically identifying and optogenetically targeting specific subsets of neurons known to be involved in fear inhibition. This project is comprised of three aims. Aim 1 determines whether extinction under the optogenetic activation of a population of cells in the lateral division of the central nucleus of the amygdala known to be involved in fear inhibition (PKC-d+ neurons) can subsequently reduce PTSD-induced enhancements in fear, increased aggression, and alterations in sexual behavior. Aim 2 determines whether optogenetic silencing of a distinct but intermingled population of neurons (CRH+ neurons) in the same brain region can produce the same reduction in PTSD symptomology. Aim 3 examines whether similar effects can be obtained using selective silencing or activation of prefrontal cortex projections to the amygdala.
This project has significant intellectual merit in its cross-disciplinary approach. Namely, it combines cutting-edgemolecular biology and genetic tools with well-designed behavioral paradigms. The application of such molecular techniques with solid behavioral design and analyses are intellectually important in terms of the extent to which these tools can be applied to behavioral neuroscience, taught, and shared with the public.
Broader Impacts: The dissection of PTSD extinction circuitry has the powerful potential to provide a highly targeted, translational approach for the treatment of anxiety disorders and phobias. In addition, this project encourages the teaching, learning and training of optogenetics and applications of molecular biology to questions within psychological science from within the publically accessible and motivated framework of PTSD treatment.
