Optogenetic control of the medial prefrontal cortex to understand and model context-mediated emotional regulation – EmOpto

The brain is adept at recording memories of traumatic events, yet these fear memories can become pathological and contribute to incapacitating anxiety disorders often triggered by contextual cues associated with the initial event. While exposure-based therapies can be useful for treating these problems, fear relapse is common afterwards. Corticolimbic brain regions, including the hippocampus and medial prefrontal cortex (mPFC), are believed to be critically involved with the pathophysiology of these anxiety disorders, and these structures are connected via a direct projection, the ventral hippocampus-to-mPFC (vHipp-mPFC) pathway. It has been proposed that this pathway is crucial for contextual-mediated emotional regulation, which might make it a key mediator in fear relapse and anxiety. Despite its potentially important role the pathway’s function in emotional regulation is not well delineated. In recent years new optogenetics strategies have been developed which provide powerful and precise control of neuron activity within behaving animals. This project is a collaboration between internationally known groups, one of which specializes in systems-level translational research. This work will utilize optogenetic strategies to control the activity of the prelimbic and infralimbic branches of the vHipp-mPFC pathway during fear renewal and anxiety protocols. This will be correlated with associated changes in, vHipp-mPFC coherence, a potentially important marker of effective information transfer between the vHipp and mPFC. The resulting knowledge will be used to develop a novel optogenetic methodology that simulates the pathophysiology in this pathway implicated in emotional dysregulation. Thus, this project seeks to understand the vHipp-mPFC pathway’s contribution to contextually-mediated emotional behavior in order to provide an evidence-based model of anxiety disorders that can be used as a target for drug development and therapeutic strategies.