Monday, September 8, 2008

mPFC neurons signal memory for fear extinction

Milad, M.R. & Quirk, G.J. (7 November 2002). Neurons in the medial prefrontal cortex signal memory for fear extinction. Nature, 420, 70-74.

Extinction is a process thought to form a new memory that inhibits the once-learned conditioned response. This paper suggests that consolidation of extinction learning potentiates activity in the infralimbic cortex (IL) of the mPFC which inhibits fear during subsequent encounters with fear stimuli. Electrophysiological recording showed that IL activity remained unresponsive during the conditioning phase and also during extinction training on Day 1. However, by Day 2, activity in the IL in response to tone was present from the start of the extinction phase. Further, stimulation of the IL paired with tone presentation resulted in less freezing behavior and also accelerated extinction learning. Therefore, enhanced extinction learning could be mediated directly by the stimulation or indirectly by the behavioral feedback of decrease freezing. Since the BLA sends excitatory projections to IL, it is possible that these inputs serve to potentiate IL neurons during the consolidation of extinction. The IL is then likely to inhibit expression of fear behavior via its projections to intercalated (ITC) cells in the CE, dampening the output of the amygdala. Pairing reminder stimuli with activation of the ventral mPFC through transcranial magnetic stimulation (TMS) might help strengthen extinction of fear in clinical settings.

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