Applying in vitro recording techniques to extinction of conditioned fear

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The ability to adapt behavioral response to environmental cues is critical for survival and requires learning to associate a given cue with a given consequence so that an appropriate response can be made. The extinction of Pavlovian fear conditioning is a commonly used model of associative learning in which an animal must learn that a neutral stimulus (tone) that was previously paired with an aversive stimulus (footshock) no longer predicts the aversive stimulus. Rather than erase fear memory, extinction is thought to form a new memory that signals safety. Activity in the medial prefrontal cortex (mPFC) is critical for the recall of fear extinction memory. In this project investigators from two Puerto Rican institutions will combine their expertise in slice recording and neural systems of fear learning to examine the intrinsic cellular mechanisms that mediate the extinction-induced enhancement of mPFC activity. The investigators will use a multidisciplinary approach combining in vitro patch-clamp electrophysiology, histology, in vivo single neuron recordings, behavioral training, and in vitro and in vivo neuropharmacology.The investigators expect to demonstrate that extinction training enhances the intrinsic excitability of mPFC neurons, that metabotropic glutamate receptor subtype 5 (mGluR5) controls the intrinsic excitability in mPFC neurons, and that the stimulation of mGluR5 receptors in vivo augments the recall of extinction memory. The results of this study will provide important groundwork for understanding how extinction memory is encoded at the level of single neurons.This project creates a unique opportunity for Puerto Rican graduate and undergraduate students to learn a multidisciplinary and collaborative approach to science. Students in both laboratories will be involved in the project and will present their results at the Society for Neuroscience Annual Meetings.