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

Abstract

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.

Transgenic Inhibition of Neuronal Protein Kinase A Activity Facilitates Fear Extinction

“…The basic demonstration in our experiments that the same genetic manipulations that impair initial memory formation may facilitate subsequent extinction is consistent with many other studies showing behavioral, systems, and molecular differences between initial learning and extinction (for review, see McNally et al, 2005;Bouton et al, 2006;Lattal et al, 2006). However, other studies have found a number of important similarities between initial learning and extinction, suggesting that a complete picture of extinction memory formation and consolidation will need to include multiple mechanisms.…”

“…Extinction appears to rely on many of these same molecular and neural systems, but a number of studies suggest that extinction may also engage different processes Cain et al, 2002;Marsicano et al, 2002;Davis et al, 2006;Lattal et al, 2006). One molecular pathway that regulates memory formation across species is the cAMP/ protein kinase A (PKA) signaling cascade.…”

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

“…In contextual fear memory, there is evidence supporting gene transcription during long-term memory extinction in amygdala and prefrontal cortex, but not in the hippocampus, suggesting that gene expression in the latter structure may not be involved (Mamiya et al, 2009). Thus, the participation of transcription factors in the consolidation of extinction is controversial and the role of hippocampus in extinction is not well understood (Lattal et al, 2006). Furthermore, the mechanisms that determine whether a reactivated memory will reconsolidate or extinguish are unknown.…”

A hippocampal Cdk5 pathway regulates extinction of contextual fear

“…A number of studies have shown that some, but not all, components of the molecular machinery that is required for the initial encoding of fear memories also regulate extinction 7-10 . Recent studies indicate that synaptic remodeling, for example, mediated by actin re-arrangement, may be important for extinction 3,6 . Actin dynamics are intimately involved in synaptic plasticity, synapse formation and neuronal morphology 6,11,12 .…”