Prefrontal-Amygdala Interactions in Fear Extinction

University Of Puerto Rico Med Sciences, San Juan PR

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Abstract

DESCRIPTION (provided by applicant): When emotions such as fear and anxiety are unregulated, several behaviors develop that are detrimental to mental and physical health. Such debilitating features are characteristic of anxiety disorders like post-traumatic stress disorder (PTSD). Biological markers of emotional regulation can be understood in an animal model involving Pavlovian fear conditioning and extinction. Fear extinction occurs when a tone that had been presented with an aversive stimulus is repeatedly presented in the absence of the stimulus. In humans, failure to extinguish fear responses is thought to contribute to PTSD and other anxiety disorders. Extinction, as a learning process, requires three phases: acquisition, consolidation, and retrieval. Recent evidence from rodent studies implicates the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) in extinction. It is unclear, however, when and how these structures interact during extinction. In Aim 1, we will determine in which phases of extinction training mPFC and BLA is necessary. This will be achieved by: 1) reversible inactivation of mPFC during different phases of extinction training;2) reversible inactivation of BLA during different phases of extinction training. Once the critical phase of BLA-mPFC interaction is determined, Aim 2 will assess the contribution of BLA to tone-evoked and spontaneous neuronal activity in IL during extinction. This will be achieved by reversible inactivation of BLA while simultaneously recording neuronal activity in mPFC during extinction. Understanding the interaction of structures necessary for fear extinction could elucidate the mechanisms of emotional regulation. Deficiencies in these mechanisms may be the underlying factors in PTSD and other anxiety disorders. PUBLIC HEALTH RELEVANCE: In humans, the inability to extinguish fear responses is believed to be an underlying factor of anxiety disorders and post-traumatic stress disorder (PTSD). This research aims to understand how and when neural structures necessary for extinction interact. Deficiencies in the physiological mechanisms between the amygdala and prefrontal cortex could be rescued, thus reducing extinction failure. This could lead to novel treatments for extinction-based therapies for PTSD.