Role of protein synthesis and DNA methylation in the consolidation and maintenance of long-term memory in Aplysia

  1. Kaycey Pearce
  2. Diancai Cai
  3. Adam C Roberts
  4. David L Glanzman  Is a corresponding author
  1. Univeristy of California, Los Angeles, United States

Abstract

Previously, we reported that long-term memory (LTM) in Aplysia can be reinstated by truncated (partial) training following its disruption by reconsolidation blockade and inhibition of PKM (Chen et al., 2014). Here, we report thatLTM can be induced by partial training after disruption of original consolidation by protein synthesis inhibition (PSI) begun shortly after training. But when PSI occurs during training, partial training cannot subsequently establish LTM. Furthermore, we find that inhibition of DNA methyltransferase (DNMT), whether during training or shortly afterwards, blocks consolidation of LTM and prevents its subsequent induction by truncated training; moreover, later inhibition of DNMT eliminates consolidated LTM. Thus, the consolidation of LTM depends on two functionally distinct phases of protein synthesis: an early phase that appears to prime LTM; and a later phase whose successful completion is necessary for the normal expression of LTM. Both the consolidation and maintenance of LTM depend on DNA methylation.

Article and author information

Author details

  1. Kaycey Pearce

    Department of Integrative Biology and Physiology, Univeristy of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Diancai Cai

    Department of Integrative Biology and Physiology, Univeristy of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Adam C Roberts

    Department of Integrative Biology and Physiology, Univeristy of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. David L Glanzman

    Department of Integrative Biology and Physiology, Univeristy of California, Los Angeles, Los Angeles, United States
    For correspondence
    glanzman@ucla.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5479-0245

Funding

National Institute of Neurological Disorders and Stroke (NIH R01 NS029563)

  • David L Glanzman

National Institute of Mental Health (NIH R01 MH096120)

  • David L Glanzman

National Science Foundation (IOS 1121690)

  • David L Glanzman

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Mani Ramaswami, Trinity College Dublin, Ireland

Version history

  1. Received: June 1, 2016
  2. Accepted: January 7, 2017
  3. Accepted Manuscript published: January 9, 2017 (version 1)
  4. Accepted Manuscript updated: January 10, 2017 (version 2)
  5. Version of Record published: February 15, 2017 (version 3)

Copyright

© 2017, Pearce et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,968
    Page views
  • 513
    Downloads
  • 60
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Kaycey Pearce
  2. Diancai Cai
  3. Adam C Roberts
  4. David L Glanzman
(2017)
Role of protein synthesis and DNA methylation in the consolidation and maintenance of long-term memory in Aplysia
eLife 6:e18299.
https://doi.org/10.7554/eLife.18299

Share this article

https://doi.org/10.7554/eLife.18299

Further reading

    1. Neuroscience
    Harry Clark, Matthew F Nolan
    Research Article

    Grid firing fields have been proposed as a neural substrate for spatial localisation in general or for path integration in particular. To distinguish these possibilities, we investigate firing of grid and non-grid cells in the mouse medial entorhinal cortex during a location memory task. We find that grid firing can either be anchored to the task environment, or can encode distance travelled independently of the task reference frame. Anchoring varied between and within sessions, while spatial firing of non-grid cells was either coherent with the grid population, or was stably anchored to the task environment. We took advantage of the variability in task-anchoring to evaluate whether and when encoding of location by grid cells might contribute to behaviour. We find that when reward location is indicated by a visual cue, performance is similar regardless of whether grid cells are task-anchored or not, arguing against a role for grid representations when location cues are available. By contrast, in the absence of the visual cue, performance was enhanced when grid cells were anchored to the task environment. Our results suggest that anchoring of grid cells to task reference frames selectively enhances performance when path integration is required.

    1. Neuroscience
    Kiwamu Kudo, Kamalini G Ranasinghe ... Srikantan S Nagarajan
    Research Article

    Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-β and misfolded tau proteins causing synaptic dysfunction, and progressive neurodegeneration and cognitive decline. Altered neural oscillations have been consistently demonstrated in AD. However, the trajectories of abnormal neural oscillations in AD progression and their relationship to neurodegeneration and cognitive decline are unknown. Here, we deployed robust event-based sequencing models (EBMs) to investigate the trajectories of long-range and local neural synchrony across AD stages, estimated from resting-state magnetoencephalography. The increases in neural synchrony in the delta-theta band and the decreases in the alpha and beta bands showed progressive changes throughout the stages of the EBM. Decreases in alpha and beta band synchrony preceded both neurodegeneration and cognitive decline, indicating that frequency-specific neuronal synchrony abnormalities are early manifestations of AD pathophysiology. The long-range synchrony effects were greater than the local synchrony, indicating a greater sensitivity of connectivity metrics involving multiple regions of the brain. These results demonstrate the evolution of functional neuronal deficits along the sequence of AD progression.