Neural Substrates of Contextual Regulation of Extinction

描述(申请人提供)：大鼠条件性恐惧的消退为创伤后应激障碍(PTSD)的治疗提供了一个有用的动物模型。消亡包括与恐惧记忆竞争的抑制性记忆的形成，以减少恐惧的表达。灭绝的标志之一是它对语境的依赖：在一个语境中习得的灭绝不会转移到另一个语境中。最近的证据表明，内侧前额叶皮质(MPFC)在消退回忆中起着至关重要的作用，背侧海马体(DHPC)在消退回忆的语境调制中也起着重要作用。在这次博士前研究期间，我将研究灭绝回忆过程中mPFC神经元活动的背景调节，并研究dHPC在调节这种背景调节中的作用。具体目标1：将测量mPFC中自发的和CS诱发的神经元活动，以确定其在信号消退环境中的作用。具体目标2：在[dHPC]失活后，将测量mPFC神经元的活动，以检查消退恢复的上下文依赖性依赖于海马-前额叶相互作用的程度。了解上下文调节消退的神经机制可能会导致对创伤后应激障碍更有效的治疗。

DESCRIPTION (provided by applicant): Extinction of conditioned fear in rats provides a useful animal model for the treatment of post-traumatic stress disorder (PTSD). Extinction involves the formation of an inhibitory memory that competes with the fear memory to reduce the expression of fear. One of the hallmarks of extinction is its context dependency: extinction learned in one context does not transfer to another. Recent evidence suggests a vital role for the medial prefrontal cortex (mPFC) in extinction recall [and a] a role for the dorsal hippocampus (dHPC) in contextual modulation of extinction recall. During this Pre-Doctoral Fellowship, I will investigate the contextual modulation of mPFC neuronal activity during extinction recall and examine the role of dHPC in mediating this contextual modulation. Specific Aim 1: Spontaneous and CS-evoked neuronal activity in mPFC will be measured to determine its role in signaling extinction contexts. Specific Aim 2: After inactivation of [dHPC], mPFC neuronal activity will be measured to examine the degree to which the context-dependency of extinction retrieval relies upon hippocampal-prefrontal interactions. Understanding the neural mechanisms of contextual regulation of extinction could lead to more effective therapies for PTSD.