Neural Substrates of Contextual Regulation of Extinction

描述（由申请人提供）：大鼠条件性恐惧的消退为治疗创伤后应激障碍（PTSD）提供了有用的动物模型。消退涉及抑制性记忆的形成，它与恐惧记忆竞争，以减少恐惧的表达。灭绝的特征之一是它的上下文依赖性：在一个上下文中学习的灭绝不会转移到另一个上下文。最近的证据表明，内侧前额叶皮层（mPFC）在灭绝回忆中起着至关重要的作用，背侧海马（dHPC）在灭绝回忆的上下文调制中起着重要的作用。在这个博士前奖学金，我将调查mPFC神经元活动的背景调制在灭绝回忆和检查dHPC在介导这种背景调制的作用。具体目标1：将测量mPFC中的自发和CS诱发的神经元活动，以确定其在信号消退背景中的作用。具体目标二：在[dHPC]失活后，将测量mPFC神经元活动，以检查消退检索的上下文依赖性依赖于前额叶-前额叶相互作用的程度。了解灭绝的背景调节的神经机制可能会导致更有效的治疗PTSD。

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.