BDNF-ergic circuits in extinction of active avoidance

描述（由申请人提供）：BDNF信号传导缺陷与灭绝失败和对PTSD的基于灭绝的疗法的不良反应有关。大脑前额叶-前额叶连接缺陷与创伤后应激障碍的严重程度相关。我们最近在大鼠中的研究表明，从腹侧海马（vHPC）到边缘下前额叶皮层（IL）的BDNF信号调节恐惧消退。我们对创伤后应激障碍相关情绪调节的理解，大部分来自实验性恐惧条件反射和消退，它们模拟了创伤后应激障碍症状的过度觉醒和重新体验。然而，关于PTSD中的过度回避，我们所知甚少。在目标1中，我们将研究BDNF信号在回避消失中的作用。在目标2中，我们将改善BDNF信号传导，以促进无法消除回避反应的大鼠的灭绝。

DESCRIPTION (provided by applicant): 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.