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Cited by 14Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchMemory Processes and Influences

Kinase and phosphatase engagement is dissociated between memory formation and extinction

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Pagani, Mario Rafael, Merlo, Emiliano·2019·Frontiers in Molecular Neuroscience
DOI 10.3389/fnmol.2019.00038PMC PMC6391346
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Abstract

Associative long-term memories (LTMs) support long-lasting behavioral changes resulting from sensory experiences. Retrieval of a stable LTM by means of a large number of conditioned stimulus (CS) alone presentations produces inhibition of the original memory through extinction. Currently, there are two opposing hypotheses to account for the neural mechanisms supporting extinction. The unlearning hypothesis posits that extinction affects the original memory trace by reverting the synaptic changes supporting LTM. On the contrary, the new learning hypothesis proposes that extinction is simply the formation of a new associative memory that inhibits the expression of the original one. We propose that detailed analysis of extinction-associated molecular mechanisms could help distinguish between these hypotheses. Here we will review experimental evidence regarding the role of protein kinases and phosphatases (K&P) on LTM formation and extinction. Even though K&P regulate both memory processes, their participation appears to be dissociated. LTM formation recruits kinases, but is constrained by phosphatases. Memory extinction presents a more diverse molecular landscape, requiring phosphatases and some kinases, but also being constrained by kinase activity. Based on the available evidence, we propose a new theoretical model for memory extinction: a neuronal segregation of K&P supports a combination of time-dependent reversible inhibition of the original memory [CS-unconditioned stimulus (US)], with establishment of a new associative memory trace (CS-noUS).

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  • Targeting of protein kinases or phosphatases can produce complementary, rather than bidirectional, effects on reconsolidation and extinction.

    “targeting of protein kinases or phosphatases can produce complementary, rather than bidirectional, effects on reconsolidation and extinction further supports the hypothesis”

    From Retrieval-Dependent Mechanisms Affecting Emotional Memory Persistence: Reconsolidation, Extinction, and the Space in Between (2020) · cites this paper as Pagani and Merlo, 2019

    The ‘Molecular Landscapes Associated with Memory Formation and Extinction’ section reports that inhibiting some kinases facilitates extinction, while other kinases and phosphatases are required for it. The comparison is with memory formation, not reconsolidation; the passages on reconsolidation in ‘Formation and Extinction of Associative Memories’ do not establish the claimed effects of targeting kinases or phosphatases across reconsolidation and extinction. Our copy provides no page numbers for these passages. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Extinction goes beyond the formation of a new CS-noUS inhibitory associative memory to more of a combination of new memory formation and inhibition of original memory.

    “extinctions go beyond the formation of a new CS-noUS inhibitory associative memory to more of a combination of new memory formation and inhibition of original memory (Pagani and Merlo, 2019).”

    From Retrieval-Dependent Mechanisms Affecting Emotional Memory Persistence: Reconsolidation, Extinction, and the Space in Between (2020) · cites this paper as Pagani and Merlo, 2019

    In “Extinction as A Combination of Memory Formation and Inhibition,” the paper proposes that extinction involves both CS-noUS memory formation and temporary inhibition of the original CS-US trace. The citing sentence presents this proposed framework more definitively than the paper, which says the evidence “suggests” it and that extinction “could be conceptualized” this way. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Authors
Pagani, M. R., & Merlo, E.
Affiliations
Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
Corresponding author
Merlo, Emiliano
ORCID
Venue
Frontiers in Molecular Neuroscience
Publisher
Frontiers Media SA
Published
2019-02-20
Volume
12
Pages
38-38
ISSN
1662-5099 (ISSN-L)
DOI
10.3389/fnmol.2019.00038
PMC
PMC6391346
OpenAlex
W2914393720
Cited by
14
References
165
Citations by year
2024: 1 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 5 · 2019: 1
FWCI
1.60
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Molecular Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Sussex Research Online (University of Sussex) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by)
  • Greater South Information System
Funders
Fondo para la Investigación Cientà­fica y Tecnológica (PRH-2016-0003, PICT-2017-0251)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
Keywords
memory extinction, long-term memory formation, protein kinases, protein phosphatase, associative memory, memory retrieval, conditioned stimulus, synaptic plasticity

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