Reconsolidation or Extinction: Transcription Factor Switch in the Determination of Memory Course After Retrieval

DE LA FUENTE, VERÓNICA; FREUDENTHAL, RAMIRO; ROMANO, ARTURO

JOURNAL OF NEUROSCIENCE

SOC NEUROSCIENCE

Lugar: new York; Año: 2011 p. 5562 - 5573

0270-6474

In fear conditioning, aversive stimuli are readily associated with contextual features. A brief re-exposure to the training context causes fear memory reconsolidation, whereas a prolonged re-exposure induces memory extinction. The regulation of hippocampal gene expression plays a key role in contextual memory consolidation and reconsolidation. However, the mechanisms that determine whether memory will reconsolidate or extinguish are not known. Here we demonstrate opposing roles for two evolutionarily- related transcription factors in the mouse hippocampus. We found that NF-κB is required for fear memory reconsolidation. Conversely, calcineurin phosphatase inhibited NF-B, and induced NFAT nuclear translocation in the transition between reconsolidation and extinction. Accordingly, the hippocampal inhibition of both calcineurin and NFAT independently impaired memory extinction, whereas inhibition of NF-B enhanced memory extinction. These findings represent the first insight into the molecular mechanisms that determine memory reprocessing after retrieval, supporting a transcriptional switch that directs memory towards reconsolidation or extinction. The precise molecular characterization of post-retrieval processes has potential importance to the development of therapeutic strategies for fear memory disorders.