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Histone deacetylase inhibitors rescue the impaired memory in terrestrial snails

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Abstract

It is becoming increasingly clear that the long-term plasticity can be regulated via histone modifications. Many studies demonstrated the role of histone acetylation in acquisition, maintenance, and extinction of long-term memory. Nonetheless, the role of histone acetylation in memory reinstatement following its disruption by antimnemonic treatments was not studied in details. In terrestrial snails, we examined effects of the histone deacetylases inhibitors (HDACi) sodium butyrate (NaB) and trichostatin A (TSA) on reinstatement of the context fear memory impaired by antimnemonic agents such as protein synthesis blocker anisomycin (ANI) + reminding or a specific inhibitor of protein-kinase Mζ, zeta inhibitory peptide (ZIP). It was observed that both NaB and TSA applications restored the ANI-impaired context memory regardless of memory reactivation, while a combination of NaB or TSA plus memory reactivation (or additional training) was necessary for the effective reinstatement of the ZIP-impaired memory. Additionally, NaB injections significantly facilitated development of long-term memory in animals with weak memory, while no effect was observed in animals with strong memory. The data obtained confirmed the assumption that histone acetylation is a critical regulatory component of memory development and reinstatement.

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Abbreviations

ANI :

Anisomycin

HAT:

Histone acetyltransferase

HDAC:

Histone deacetylase

HDACi:

Histone deacetylases inhibitor

NaB:

Sodium butyrate

PKMζ:

Protein-kinase Mζ

PSB:

Protein synthesis blocker

TSA:

Trichostatin A

ZIP:

Zeta inhibitory peptide

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Acknowledgements

This study was partially funded within the state assignment of Ministry of Education and Science of the Russian Federation for 2019–2021, and a grant of Russian Science Foundation 19-75-10067 (experiments with sodium butyrate).

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Authors and Affiliations

  1. Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, Russia

    Alena B. Zuzina, Alia Kh. Vinarskaya & Pavel M. Balaban

Authors
  1. Alena B. Zuzina
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  2. Alia Kh. Vinarskaya
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  3. Pavel M. Balaban
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The authors contributed equally. All authors read and approved the final manuscript.

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Correspondence to Alena B. Zuzina.

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The authors declare that they have no conflict of interest.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving snails were in accordance with the ethical standards and approved (#012 from 10.10.2014) by Ethical Committee of the Institute of Higher Nervous Activity and Neurophysiology of Russian Academy of Sciences.

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Zuzina, A.B., Vinarskaya, A.K. & Balaban, P.M. Histone deacetylase inhibitors rescue the impaired memory in terrestrial snails. J Comp Physiol A 206, 639–649 (2020). https://doi.org/10.1007/s00359-020-01422-w

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  • DOI: https://doi.org/10.1007/s00359-020-01422-w

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