Deficient BDNF signaling has been associated with extinction failure and with a poor response to extinction- based therapies for PTSD. Deficient hippocampal-prefrontal connectivity has been correlated with PTSD severity. Our recent work in rats suggests that BDNF signaling from the ventral hippocampus (vHPC) to the infralimbic prefrontal cortex (IL) modulates fear extinction. Much of what we understand about the emotional regulation related to PTSD comes from experimental fear conditioning and extinction, which model the hyperarousal and re-experiencing of symptoms of PTSD. Much less is known, however, about excessive avoidance seen in PTSD.
In Aim 1, we will investigate the role of BDNF signaling in extinction of avoidance.
In Aim 2, we will improve BDNF signaling to facilitate extinction in rats unable to extinguish avoidance responses.
This research will explore the role of BDNF circuitry in the extinction of avoidance behaviors. Understanding the mechanisms underlying extinction of avoidance will help us understand the circuits of excessive avoidance in PTSD. The knowledge derived from the proposed experiments will contribute to improvement of exposure- based therapies for refractory PTSD. Furthermore, our findings will help develop novel therapeutic approaches for mental disorders characterized by excessive avoidance.
|Rosas-Vidal, Luis E; Lozada-Miranda, Valeria; Cantres-Rosario, Yisel et al. (2018) Alteration of BDNF in the medial prefrontal cortex and the ventral hippocampus impairs extinction of avoidance. Neuropsychopharmacology 43:2636-2644|
|Bravo-Rivera, Christian; Diehl, Maria M; Roman-Ortiz, Ciorana et al. (2015) Long-range GABAergic neurons in the prefrontal cortex modulate behavior. J Neurophysiol 114:1357-9|
|Rosas-Vidal, L E; Rodriguez-Romaguera, J; Do-Monte, F H et al. (2015) Targeting the reconsolidation of extinction memories: a novel potential strategy to treat anxiety disorders. Mol Psychiatry 20:1264-5|