A computational model of systems memory consolidation and reconsolidation

Helfer, Peter; Shultz, Thomas R.

doi:10.1002/hipo.23187

Cited by 7 publications

(4 citation statements)

References 160 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As we have speculated previously, these considerations suggest that destabilisation may not be an allor-nothing process, but proportional to the magnitude of the PE 'updating signal', an idea for which contemporary computational models of reconsolidation (Gershman et al, 2017;Helfer and Shultz, 2017;Osan et al, 2011) and empirical evidence (Reichelt and Lee, 2013) provide some support. Importantly, this relationship between PE and destabilisation need not be linear.…”

Section: Discussionmentioning

confidence: 57%

Nitrous oxide may interfere with the reconsolidation of drinking memories in hazardous drinkers in a prediction-error-dependent manner

Das

Walsh

Hannaford

et al. 2018

European Neuropsychopharmacology

View full text Add to dashboard Cite

Weakening drinking-related reward memories by blocking their reconsolidation is a potential novel strategy for treating alcohol use disorders. However, few viable pharmacological options exist for reconsolidation interference in humans. We therefore examined whether the NMDA receptor antagonising gas, Nitrous Oxide (NO) could reduce drinking by preventing the post-retrieval restabilisation of alcohol memories in a group of hazardous drinkers. Critically, we focussed on whether prediction error (PE; a key determinant of reconsolidation) was experienced at retrieval. Sixty hazardous drinkers were randomised to one of three groups that retrieved alcohol memories either with negative PE (Retrieval + PE), no PE (Retrieval no PE) or non-alcohol memory retrieval with PE (No-retrieval +PE). All participants then inhaled 50% NO for 30 min. The primary outcome was change in beer consumption and alcohol cue-driven urge to drink from the week preceding manipulation (baseline) to the week following manipulation (test). The manipulation did not affect drinking following the intended retrieval+/- PE conditions However, a manipulation check, using a measure of subjective surprise, revealed that the group-level manipulation did not achieve the intended differences in PE at retrieval. Assessment of outcomes according to whether alcohol-relevant PE was actually experienced at retrieval, showed NO produced reductions in drinking in a retrieval and PE-dependent fashion. These preliminary findings highlight the importance of directly testing assumptions about memory reactivation procedures in reconsolidation research and suggest that NO should be further investigated as a potential reconsolidation-blocking agent.

show abstract

Section: Discussionmentioning

confidence: 57%

Nitrous oxide may interfere with the reconsolidation of drinking memories in hazardous drinkers in a prediction-error-dependent manner

Das

Walsh

Hannaford

et al. 2018

European Neuropsychopharmacology

View full text Add to dashboard Cite

show abstract

“…For reviews of reconsolidation research, see [22][23][24]. For a computational model of systems consolidation and reconsolidation, see [25].…”

Section: Introductionmentioning

confidence: 99%

Coupled feedback loops maintain synaptic long-term potentiation: A computational model of PKMzeta synthesis and AMPA receptor trafficking

Helfer

Shultz

2018

PLoS Comput Biol

Self Cite

View full text Add to dashboard Cite

In long-term potentiation (LTP), one of the most studied types of neural plasticity, synaptic strength is persistently increased in response to stimulation. Although a number of different proteins have been implicated in the sub-cellular molecular processes underlying induction and maintenance of LTP, the precise mechanisms remain unknown. A particular challenge is to demonstrate that a proposed molecular mechanism can provide the level of stability needed to maintain memories for months or longer, in spite of the fact that many of the participating molecules have much shorter life spans. Here we present a computational model that combines simulations of several biochemical reactions that have been suggested in the LTP literature and show that the resulting system does exhibit the required stability. At the core of the model are two interlinked feedback loops of molecular reactions, one involving the atypical protein kinase PKMζ and its messenger RNA, the other involving PKMζ and GluA2-containing AMPA receptors. We demonstrate that robust bistability–stable equilibria both in the synapse’s potentiated and unpotentiated states–can arise from a set of simple molecular reactions. The model is able to account for a wide range of empirical results, including induction and maintenance of late-phase LTP, cellular memory reconsolidation and the effects of different pharmaceutical interventions.

show abstract

“…Consistent with the reconsolidation theory, it has been observed that the earlier the intervention is performed after memory retrieval, the weaker the memory trace will be reconsolidated (Helfer and Shultz 2019). For instance, MK801 impaired procedural memory reconsolidation when administered up to 90 min after retrieval and anisomycin caused passive-avoidance amnesia in mice when injected 30 min or less after memory reactivation (Judge and Quartermain 1982;Przybyslawski and Sara 1997).…”

Section: Discussionmentioning

confidence: 73%

The role of prelimbic and anterior cingulate cortices in fear memory reconsolidation and persistence depends on the memory age

et al. 2020

View full text Add to dashboard Cite

Reconsolidation is a time-limited process under which reactivated memory content can be modified. Works focused on studying reconsolidation mainly restrict intervention to the moments immediately after reactivation and to recently acquired memories. However, the brain areas activated during memory retrieval depend on when it was acquired, and it is relatively unknown how different brain sites contribute to reconsolidation and persistence of reactivated recent and remote fear memories. Here, we sought to investigate the participation of prelimbic (PL) and anterior cingulate cortices (ACC) in recent (1 d old) and remote (21 d old) fear memory reconsolidation and persistence. Male Wistar rats were submitted to the contextual fear conditioning protocol. Tamoxifen (TMX), an estrogen receptor modulator known to inhibit protein kinase C activity was used to interfere with these processes. When infused into the PL cortex, but not into the ACC, TMX administration immediately or 6 h after recent fear memory reactivation impaired memory reconsolidation and persistence, respectively. TMX administered immediately after remote memory reactivation impaired memory reconsolidation when infused into the PL cortex and ACC. However, remote memory persistence was only affected when TMX was infused 6 h after memory reactivation into the ACC and no effect was observed when TMX was infused 6 h after memory reactivation into PL cortex. Together, the findings provide further evidence on the participation of PL cortex and ACC in reconsolidation of recent and remote fear memories and suggest that the persistence of a reactivated fear memory becomes independent on the PL cortex with memory age and dependent on the ACC.

show abstract

A computational model of systems memory consolidation and reconsolidation

Cited by 7 publications

References 160 publications

Nitrous oxide may interfere with the reconsolidation of drinking memories in hazardous drinkers in a prediction-error-dependent manner

Nitrous oxide may interfere with the reconsolidation of drinking memories in hazardous drinkers in a prediction-error-dependent manner

Coupled feedback loops maintain synaptic long-term potentiation: A computational model of PKMzeta synthesis and AMPA receptor trafficking

The role of prelimbic and anterior cingulate cortices in fear memory reconsolidation and persistence depends on the memory age

Contact Info

Product

Resources

About