?s abstract): A commonly used animal model of anxiety disorders is fear conditioning. In this paradigm, a neutral stimulus such as tone is paired with an aversive stimulus such as footshock. This pairing induces fearful responses to the tone. Following acquisition of fear conditioning, subsequent presentations of the tone cause fear responses to extinguish. Failure to extinguish fear has been proposed as a basis for anxiety disorders such as post-traumatic stress disorder (PTSD). The medial prefrontal cortex (mPFC) has been implicated in extinction. We recently showed that lesions of the vmPFC did not affect extinction over short time intervals, but blocked the recall of extinction after a 24-hour delay. There are two hypotheses that could explain the role of the vmPFC in recall of extinction: 1) VmPFC could be involved in signaling an inhibitory association between CS and US during extinction recall. 2) Alternatively, vmPFC could be signaling the extinguished context. Previous work has shown that in order to express extinction, rats must recall the context where extinction learning took place. To distinguish between these hypotheses, single-unit activity in the vmPFC will be recorded using tetrodes during fear conditioning. Tone-evoked responses as well as spontaneous activity will be recorded before and after extinction. Hypothesis 1: if the vmPFC were involved in signaling an inhibitory association between the CS and the US, tone-evoked responses of vmPFC neurons would change during extinction. Hypothesis 2: if the vmPFC were signaling extinguished contexts, a change in spontaneous firing rate during or after extinction would be expected. This proposed study will bring us closer to understanding the mechanisms of fear extinction. Facilitation of extinction processes in patients with disorders such as PTSD could potentially help in curing such disorders.
| Milad, M R; Vidal-Gonzalez, I; Quirk, G J (2004) Electrical stimulation of medial prefrontal cortex reduces conditioned fear in a temporally specific manner. Behav Neurosci 118:389-94 |
