Functional imaging studies in PTSD patients suggest that reduced activation of the medial prefrontal cortex (mPFC) contributes to the excessive fear response seen in these patients. To understand why the mPFC is less activated in PTSD patients, we need to understand the mechanisms by which fear conditioning and extinction alter mPFC excitability. Patch-clamp recordings of infralimbic (IL) neurons in the mPFC revealed that the intrinsic excitability of IL neurons was depressed by fear conditioning in rats. The depressed IL excitability could reduce IL activation and enhance conditioned fear responses. Consistent with this, reducing IL intrinsic excitability enhances conditioned fear response. These findings imply that intrinsic plasticity in IL contributes to the consolidation of the conditioned fear memory. Currently we are working to extend these results by examining the mechanisms and circuits involved in this fear conditioning-induced depression of IL intrinsic excitability. A better understanding of the mechanisms leading to intrinsic plasticity in this brain structure may provide direction for the development of novel treatments for PTSD.
Rather than erase fear memory, extinction is thought to form a new memory that signals safety. The goal of this project is to understand how extinction memory is encoded at the level of single neurons. Since a growing body of literature implicates enhanced activity in the infralimbic region (IL) of the medial prefrontal cortex in the retention of fear extinction, we are examining the intrinsic and synaptic mechanisms that mediate the enhanced activity of the IL neurons after extinction training. We are applying a multidisciplinary approach combining patch-clamp electrophysiology in brain slices, histology, behavioral training, molecular techniques, optogenetics and in vitro and in vivo neuropharmacology.