Memory extinction entails the inhibition of the transcription factor NF-κB

• Autores: Merlo, E.; Romano, A.
• Año de publicación: 2008
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: PLoS ONE 2008;3(11)
• Materia: immunoglobulin enhancer binding protein; salazosulfapyridine; immunoglobulin enhancer binding protein; article; brain function; controlled study; gene expression; memory consolidation; memory disorder; molecular mechanics; nonhuman; pharmacological blocking; transcription initiation; working memory; animal; Brachyura; drug antagonism; long term memory; male; memory; metabolism; physiology; reinforcement; Animalia; Decapoda (Crustacea); Animals; Brachyura; Extinction, Psychological; Male; Memory; NF-kappa B; Retention (Psychology)
• Institución: Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales

In contextual memories, an association between a positive or negative reinforcement and the contextual cues where the reinforcement occurs is formed. The re-exposure to the context without reinforcement can lead to memory extinction or reconsolidation, depending on the number of events or duration of a single event of context re-exposure. Extinction involves the temporary waning of the previously acquired conditioned response. The molecular processes underlying extinction and the mechanisms which determine if memory will reconsolidate or extinguish after retrieval are not well characterized, particularly the role of transcription factors and gene expression. Here we studied the participation of a transcription factor, NF-κB, in memory extinction. In the crab context-signal memory, the activation of NF-κB plays a critical role in consolidation and reconsolidation, memory processes that are well characterized in this model. The administration of a NF-κB inhibitor, sulfasalazine prior to extinction session impeded spontaneous recovery. Moreover, reinstatement experiments showed that the original memory was not affected and that NF-κB inhibition by sulfasalazine impaired spontaneous recovery strengthening the ongoing memory extinction process. Interestingly, in animals with fully consolidated memory, a brief re-exposure to the training context induced neuronal NF-κB activation and reconsolidation, while prolonged re-exposure induced NF-κB inhibition and memory extinction. These data constitutes a novel insight into the molecular mechanisms involved in the switch between memory reconsolidation and extinction. Moreover, we propose the inhibition of NF-κB as the engaged mechanism underlying extinction, supporting a novel approach for the pharmacological enhancement of this memory process. The accurate description of the molecular mechanisms that support memory extinction is potentially useful for developing new strategies and drug candidates for therapeutic treatments of the maladaptive memory disorders such as post-traumatic stress, phobias, and drug addiction. © 2008 Merlo, Romano.
Fil:Merlo, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Romano, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.