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

Department of Behavioral Neuroscience and Portland Alcohol Research Center, Oregon Health & Science University, Portland, Oregon 97239, USA.
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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    • "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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    ABSTRACT: We recently reported two novel breeding lines of rats known as Carioca High- and Low-conditioned Freezing (CHF and CLF), based on defensive freezing responses to contextual cues previously associated with electric footshock. The present study used animals of the 8th generation of our selective breeding program to investigate both contextual fear extinction and re-extinction. The results consistently showed that CHF animals froze more than CLF animals. Long extinction training was able to extinguish phenotypic differences between lines, but the divergence was restored after just one fear reacquisition training session. These differences disappeared again during re-extinction training. The possible neural mechanisms involved in these two types of learning are discussed
    World Journal of Neuroscience 06/2014; 4(3). DOI:10.4236/wjns.2014.43028
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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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    ABSTRACT: The inhibitor κB protein kinase/nuclear factor κB (IKK/NF-κB) signaling pathway is critical for synaptic plasticity. However, the role of IKK/NF-κB in drug withdrawal-associated conditioned place aversion (CPA) memory is unknown. Here, we showed that inhibition of IKK/NF-κB by sulphasalazine (SSZ; 10 mM, i.c.v.) selectively blocked the extinction but not acquisition or expression of morphine-induced CPA in rats. The blockade of CPA extinction induced by SSZ was abolished by sodium butyrate, an inhibitor of histone deacetylase. Thus, the IKK/NF-κB signaling pathway might play a critical role in the extinction of morphine-induced CPA in rats and might be a potential pharmacotherapy target for opiate addiction.
    PLoS ONE 06/2012; 7(6):e39696. DOI:10.1371/journal.pone.0039696 · 3.23 Impact Factor
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    • "In humans, the phenomenon of fear extinction is exploited by clinical therapies for anxiety disorders, in which patients learn to reduce responses to fear-arousing stimuli by repeated unreinforced exposures (Marks, 1979; de Silva and Rachman, 1983; Mineka, 1985; Davey, 1997; Bouton et al., 2001; Eelen and Vervliet, 2006; Craske et al., 2008). Evidence indicates that fear extinction does not simply " erase " the previously learned CS–US association, but instead forms a new memory that the CS has become safe, which inhibits expression of the original fear memory (Pavlov, 1927; Konorski, 1948; for review, see Lattal et al., 2006; but see also Kim et al., 2007). Supporting this, it is well established that after extinction, conditional fear responses to a CS can re-emerge without any additional CS–US pairings by the mere passage of time (spontaneous recovery; Pavlov, 1927; Robbins, 1990), by presenting the extinguished CS in a context other than the extinction context (renewal; Bouton and Bolles, 1979; Bouton and King, 1983), or by non-contingent presentations of the US (reinstatement; Rescorla and Heth, 1975; Bouton and Bolles, 1979). "
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