Extinction, applied after retrieval of auditory fear memory, selectively increases zinc-finger protein 268 and phosphorylated ribosomal protein S6 expression in prefrontal cortex and lateral amygdala

Tedesco, Vincenzo; Roquet, Rheall F.; Demis, John; Chiamulera, Cristiano; Monfils, Marie‐H.

doi:10.1016/j.nlm.2014.08.015

Cited by 48 publications

(43 citation statements)

References 30 publications

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“…The latter finding is significant in that it indicates a reversal of the synaptic changes that occurred during conditioning, supporting the view that the Monfils-Schiller paradigm results in unlearning of the original CS-US association. Furthermore, the Monfils-Schiller paradigm has been shown to induce neural modifications that are distinct from standard extinction (Lee et al, 2015; Tedesco et al, 2014). …”

Section: Discussionmentioning

confidence: 99%

The computational nature of memory modification

Gershman

Monfils

Norman

et al. 2017

eLife

118

112

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Retrieving a memory can modify its influence on subsequent behavior. We develop a computational theory of memory modification, according to which modification of a memory trace occurs through classical associative learning, but which memory trace is eligible for modification depends on a structure learning mechanism that discovers the units of association by segmenting the stream of experience into statistically distinct clusters (latent causes). New memories are formed when the structure learning mechanism infers that a new latent cause underlies current sensory observations. By the same token, old memories are modified when old and new sensory observations are inferred to have been generated by the same latent cause. We derive this framework from probabilistic principles, and present a computational implementation. Simulations demonstrate that our model can reproduce the major experimental findings from studies of memory modification in the Pavlovian conditioning literature.DOI: http://dx.doi.org/10.7554/eLife.23763.001

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Section: Discussionmentioning

confidence: 99%

The computational nature of memory modification

Gershman

Monfils

Norman

et al. 2017

eLife

118

112

View full text Add to dashboard Cite

show abstract

“…We do not believe this could be the case. Recent studies have indeed shown that post-retrieval extinction engages mechanisms that are distinct from “standard” extinction (Monfils et al, 2009; Clem and Huganir, 2010; Rao-Ruiz et al, 2011; Tedesco et al, 2014; Lee et al, 2016). One explanation of memory updating is that an experience that both evokes a memory for and greatly resembles a previous experience (i.e., possess the same latent causes) is likely to be integrated with the previous memory.…”

Section: Discussionmentioning

confidence: 99%

Reconsolidation-Extinction Interactions in Fear Memory Attenuation: The Role of Inter-Trial Interval Variability

Auchter

Cormack

Niv

et al. 2017

Front. Behav. Neurosci.

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Fear extinction typically results in the formation of a new inhibitory memory that suppresses the original conditioned response. Evidence also suggests that extinction training during a retrieval-induced labile period results in integration of the extinction memory into the original fear memory, rendering the fear memory less susceptible to reinstatement. Here we investigated the parameters by which the retrieval-extinction paradigm was most effective in memory updating. Specifically, we manipulated the inter-trial intervals (ITIs) between conditional stimulus (CS) presentations during extinction, examining how having interval lengths with different degrees of variability affected the strength of memory updating. We showed that randomizing the ITI of CS presentations during extinction led to less return of fear via reinstatement than extinction with a fixed ITI. Subjects who received variable ITIs during extinction also showed higher freezing during the ITI, indicating that the randomization of CS presentations led to a higher general reactivity during extinction, which may be one potential mechanism for memory updating.

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“…For example, compared to conventional extinction, retrieval-extinction is associated with diminished involvement of the human ventromedial prefrontal cortex (vmPFC), as measured by functional neuroimaging, suggesting a potential disengagement of pathways associated with new inhibitory CS learning [80]. In contrast, increased expression of protein kinase M ζ (PKMζ) [78] and zinc-finger 268 (Zif268) in rodent vmPFC [84] is consistent with enhanced extinction of appetitive memory in this paradigm. Most interestingly, increased expression of phosphorylated ribosomal protein S6 (rpS6P) is specifically observed in both the lateral amygdala and mPFC after retrieval-extinction, but not extinction or retrieval alone (conditions equivalent to extinction and reconsolidation controls) [84].…”

Section: Discrimination On the Basis Of Biochemical Mechanismsmentioning

confidence: 99%

“…In contrast, increased expression of protein kinase M ζ (PKMζ) [78] and zinc-finger 268 (Zif268) in rodent vmPFC [84] is consistent with enhanced extinction of appetitive memory in this paradigm. Most interestingly, increased expression of phosphorylated ribosomal protein S6 (rpS6P) is specifically observed in both the lateral amygdala and mPFC after retrieval-extinction, but not extinction or retrieval alone (conditions equivalent to extinction and reconsolidation controls) [84]. Among the potential upstream regulators of rpS6P is metabotropic glutamate receptor 1 (mGlu1) [85], which has been independently implicated in both persistent threat memory attenuation and synaptic weakening after retrieval-extinction [21].…”

Section: Discrimination On the Basis Of Biochemical Mechanismsmentioning

confidence: 99%

New Learning and Unlearning: Strangers or Accomplices in Threat Memory Attenuation?

Clem

Schiller

2016

Trends in Neurosciences

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To achieve greatest efficacy, therapies for attenuating fear and anxiety should preclude the re-emergence of emotional responses. Of relevance to this aim, preclinical models of threat memory reduction are considered to engage one of two discrete neural processes: either establishment of a new behavioral response that competes with, and thereby temporarily interferes with expression of, an intact threat memory (new learning), or one which modifies and thereby disrupts an intact threat memory (unlearning). We contend that a strict dichotomy of new learning and unlearning does not provide a compelling explanation for current data. Instead, we suggest the evidence warrants consideration of alternative models that assume cooperation rather than competition between formation of new cellular traces and the modification of preexisting ones.

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Extinction, applied after retrieval of auditory fear memory, selectively increases zinc-finger protein 268 and phosphorylated ribosomal protein S6 expression in prefrontal cortex and lateral amygdala

Cited by 48 publications

References 30 publications

The computational nature of memory modification

The computational nature of memory modification

Reconsolidation-Extinction Interactions in Fear Memory Attenuation: The Role of Inter-Trial Interval Variability

New Learning and Unlearning: Strangers or Accomplices in Threat Memory Attenuation?

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