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Erasing fear memories — key receptor and essential timeframe discovered

Authors: Shigenori Kawahara
DOI: 10.1038/aps.2010.215


It is clinically important to suppress or inhibit traumatic memories, which are formed after fearful experiences. In animal models, fear memory is formed by repetitive presentation of a tone paired with an electrical foot-shock1. It is well known that an extinction protocol, in which the tone is repeatedly presented without the foot-shock, gradually decreases the pre-acquired fear response to the tone. However, this fear extinction protocol is not sufficient to erase the fear memory; fear responses may recover spontaneously or relapse under some conditions. If the fear memory is retrieved or reactivated by a single presentation of the tone without the shock 1 h before the extinction session, the fear responses are permanently removed by this retrieval–extinction protocol2. This suggests that a critical brain state is caused by the retrieval procedure, in which the fear memory becomes labile and can be destroyed by the subsequent extinction procedure. Clem and Huganir3 have found a critical receptor for the permanent erasure of fear memories by this retrieval–extinction protocol. They focused on the Ca2+-permeable type of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (Ca2+-permeable-AMPAR) located in the lateral amygdala, an essential region of the brain for learning. They suggested that removal of Ca2+-permeable-AMPARs, the content of which in the synapses is elevated for a few days after fear conditioning, is responsible for the permanent erasure of the fear memory by that protocol.

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