Neural Substrates of Contextual Regulation of Extinction

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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.