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PARP-1 activity is required for the reconsolidation and extinction of contextual fear memory

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Inaba, Hiroyoshi, Tsukagoshi, Akinori, Kida, Satoshi·2015·Molecular Brain
DOI 10.1186/s13041-015-0153-7PMC PMC4608138
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Abstract

BACKGROUND: Memory consolidation, reconsolidation, and extinction have been shown to require new gene expression. Poly ADP-ribosylation mediated by poly (ADP-ribose) polymerase-1 (PARP-1) is known to regulate transcription through histone modification. Recent studies have suggested that PARP-1 positively regulates the formation of long-term memory (LTM); however, the roles of PARP-1 in memory processes, especially processes after retrieval, remain unknown. RESULTS: Here, we show critical roles for PARP-1 in the consolidation, reconsolidation, and extinction of contextual fear memory in mice. We examined the effects of pharmacological inhibition of PARP-1 activity in the hippocampus or medial prefrontal cortex (mPFC) on these memory processes. Similarly with previous findings, a micro-infusion of the PARP-1 inhibitor 3-aminobenzamide or PJ34 into the dorsal hippocampus, but not mPFC, impaired LTM formation without affecting short-term memory (STM). Importantly, this pharmacological blockade of PARP-1 in the dorsal hippocampus, but not mPFC, also disrupted post-reactivation LTM without affecting post-reactivation STM. Conversely, micro-infusion of the PARP-1 inhibitors into the mPFC, but not dorsal hippocampus, blocked long-term extinction. Additionally, systemic administration of the PARP-1 inhibitor Tiq-A blocked c-fos induction in the hippocampus, which is observed when memory is consolidated or reconsolidated, and also blocked c-fos induction in the mPFC, which is observed when memory is extinguished. CONCLUSIONS: Our observations showed that PARP-1 activation is required for the consolidation, reconsolidation, and extinction of contextual fear memory and suggested that PARP-1 contributes to the new gene expression necessary for these memory processes.

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  • Threat extinction requires transcriptional processes within IL.

    “Threat extinction also requires transcriptional processes within IL: injection of an inhibitor of PARP-1, a gene involved in ADP-ribosylaton that is necessary for transcription, into mPFC impairs contextual threat extinction [58].”

    From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [58]

    The Results section ('PARP-1 activity in the mPFC is required for the long-term extinction of contextual fear memory'; page unavailable) reports that infusing PARP-1 inhibitors into the mPFC impaired long-term contextual fear extinction. A separate Results section reports reduced c-fos induction in both IL and PL after systemic inhibition. The paper therefore supports an mPFC gene-expression role, but does not establish that the required transcriptional processes are specifically within IL. (LLM, conf=0.87)

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Authors
Inaba, H., Tsukagoshi, A., & Kida, S.
Affiliations
Tokyo University of Agriculture (JP)
Corresponding author
Kida, Satoshi
ORCID
Venue
Molecular Brain
Publisher
Springer Science and Business Media LLC
Published
2015-10-15
Volume
8
Issue
1
Pages
63-63
ISSN
1756-6606 (ISSN-L)
DOI
10.1186/s13041-015-0153-7
PMC
PMC4608138
OpenAlex
W1712523590
Cited by
45
References
5
Citations by year
2026: 4 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 2 · 2021: 5 · 2020: 4 · 2019: 2 · 2018: 3 · 2017: 9 · 2016: 3
FWCI
3.01
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Brain (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Japan Society for the Promotion of Science (15H02488, 23300120/20380078, 24650172, 18022038/22022039, 24116008/24116001/23115716)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (306896/2014-1)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
PARP1, contextual fear memory, memory reconsolidation, fear extinction, memory consolidation, long-term memory, hippocampus, medial prefrontal cortex, 3-aminobenzamide, PJ34, c-fos, histone modifications
MeSH terms
Poly(ADP-ribose) Polymerase Inhibitors, Animals, Anxiety, Behavior, Animal, Enzyme Activation, Extinction, Psychological, Fear, Gene Expression Regulation, Hippocampus, Male, Memory, Mice, Inbred C57BL, Motor Activity, Poly(ADP-ribose) Polymerases, Proto-Oncogene Proteins c-fos, Prefrontal Cortex

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