Functional imaging studies in PTSD patients suggest that reduced activation of the medial prefrontal cortex (mPFC) contributes to the excessive fear response seen in these patients. To understand why the mPFC is less activated in PTSD patients, we need to understand the mechanisms by which fear conditioning and extinction alter mPFC excitability. Patch-clamp recordings of infralimbic (IL) neurons in the mPFC revealed that the intrinsic excitability of IL neurons was depressed by fear conditioning in rats. The depressed IL excitability could reduce IL activation and enhance conditioned fear responses. Consistent with this, reducing IL intrinsic excitability enhances conditioned fear response. These findings imply that intrinsic plasticity in IL contributes to the consolidation of the conditioned fear memory. The goal of this proposal is to extend these results by examining the mechanisms and circuits involved in this fear conditioning-induced depression of IL intrinsic excitability.
In Aim1, the role of NMDA receptors, D2-like dopamine receptors, and glucocorticoid receptors in the fear conditioning-induced depression of IL intrinsic excitability will be examined.
In Aim 2, the role of hippocampal inputs in the fear conditioning-induced depression of IL excitability will be evaluated.
In Aim 3, we will evaluate whether sustained voltage-gated K+ channels contribute to the fear conditioning-induced depression of IL excitability. A better understanding of the mechanisms leading to intrinsic plasticity in this brain structure may provide direction for the development of novel treatments for PTSD.
Reduced activation of the medial prefrontal cortex contributes to excessive fear responses in patients with PTSD and phobias. This research aims to examine the receptors, ion channels, and circuits which depress medial prefrontal cortex excitability in animals during fear conditioning. A better understanding of how fear conditioning depresses this brain structure may lead to better treatments for PTSD.
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