9YExtinction: Does It or Doesn't It? The Requirement of Altered Gene Activity and New Protein Synthesis

Department of Psychiatry and Behavioral Sciences , Northwestern University, Evanston, Illinois, United States
Biological Psychiatry (Impact Factor: 10.26). 09/2006; 60(4):344-51. DOI: 10.1016/j.biopsych.2006.05.038
Source: PubMed


Many accounts of memory suggest that an initial learning experience initiates a cascade of cellular and molecular events that are required for the consolidation of memory from a labile into a more permanent state. Studies of memory in many species have routinely found that altered gene activity and new protein synthesis are the critical components of this memory consolidation process. During extinction, when organisms learn that previously established relations between stimuli have been severed, new memories are formed and consolidated. However, the nature of the learning that underlies extinction remains unclear and there are many processes that may contribute to the weakening of behavior that occurs during extinction. In this review, we suggest that the molecular mechanisms that underlie extinction may differ depending on the learning process that is engaged by extinction. We review evidence that extinction, like initial learning, requires transcription and translation, as well as evidence that extinction occurs when protein synthesis is inhibited. We suggest that extinction occurs through the interaction of multiple behavioral and molecular mechanisms.

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    • "And, similarly to learning the original association, long-term retention of extinction training requires both RNA and Frontiers in Behavioral Neuroscience | www.frontiersin.orgprotein synthesis across several learning paradigms and species (reviewed inLattal et al., 2006). But, since extinction also involves reactivation of the original memory, the integrity of the original memory is vulnerable to disruption through reconsolidation mechanisms. "
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    • "Fear extinction has been shown to be mediated by specific neuronal circuits that are integrated in well-defined neural circuitry, including the amygdala, medial prefrontal cortex, and hippocampus [6]-[11]. Moreover, fear extinction requires many of the same cellular processes as memory reconsolidation, such as protein synthesis (protein kinase A and mitogen-activated protein kinase) and the activation of N-methyl-D-aspartate (NMDA) and β-adrenergic receptors [8]-[12]. Interestingly, recent findings indicated that a second extinction procedure after fear reacquisition, defined as re-extinction, is not mediated by the same cellular processes as fear extinction [13]. "
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    • "Behavioral extinction training effectively abolished the expression of morphine-induced CPA [7]. Interestingly, recent evidence suggested that extinction training as a new memory did not erase but rather suppressed the conditioned response [9], [10]. The exploration of the underlying mechanism is important to prevent relapse induced by anhedonia and the aversive consequences of drug withdrawal. "
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