INVESTIGADORES
FREUDENTHAL Ramiro A. M.
artículos
Título:
Reconsolidation or extinction: transcription factor switch in the determination of memory course after retrieval.
Autor/es:
DE LA FUENTE VERONICA; FREUDENTHAL R,; ROMANO ARTURO
Revista:
JOURNAL OF NEUROSCIENCE
Editorial:
SOC NEUROSCIENCE
Referencias:
Lugar: Washington, DC; Año: 2011 vol. 31 p. 5562 - 5573
ISSN:
0270-6474
Resumen:
In fear conditioning, aversive stimuli are readily associated with
contextual features. A brief reexposure to the training context causes
fear memory reconsolidation, whereas a prolonged reexposure 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 nuclear factor-κB (NF-κB) is required for
fear memory reconsolidation. Conversely, calcineurin phosphatase
inhibited NF-κB and induced nuclear factor of activated T-cells (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-κB 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 toward reconsolidation or extinction. The precise molecular
characterization of postretrieval processes has potential importance to
the development of therapeutic strategies for fear memory disorders.