Axon TRAP reveals learning-associated alterations in cortical axonal mRNAs in the lateral amgydala

  1. Linnaea E Ostroff  Is a corresponding author
  2. Emanuela Santini
  3. Robert Sears
  4. Zachary Deane
  5. Rahul N Kanadia
  6. Joseph E LeDoux
  7. Tenzin Lhakhang
  8. Aristotelis Tsirigos
  9. Adriana Heguy
  10. Eric Klann  Is a corresponding author
  1. University of Connecticut, United States
  2. Karolinska Institutet, Sweden
  3. New York University, United States
  4. New York University School of Medicine, United States

Abstract

Local translation can support memory consolidation by supplying new proteins to synapses undergoing plasticity. Translation in adult forebrain dendrites is an established mechanism of synaptic plasticity and is regulated by learning, yet there is no evidence for learning-regulated protein synthesis in adult forebrain axons, which have traditionally been believed to be incapable of translation. Here we show that axons in the adult rat amygdala contain translation machinery, and use translating ribosome affinity purification (TRAP) with RNASeq to identify mRNAs in cortical axons projecting to the amygdala, over 1200 of which were regulated during consolidation of associative memory. Mitochondrial and translation-related genes were upregulated, whereas synaptic, cytoskeletal, and myelin-related genes were downregulated; the opposite effects were observed in the cortex. Our results demonstrate that axonal translation occurs in the adult forebrain and is altered after learning, supporting the likelihood that local translation is more a rule than an exception in neuronal processes.

Data availability

Sequencing data have been deposited in GEO under accession code GSE124592. All analyses are included in supporting files.

The following data sets were generated

Article and author information

Author details

  1. Linnaea E Ostroff

    Department of Physiology and Neurobiology, University of Connecticut, Storrs, United States
    For correspondence
    linnaea.ostroff@uconn.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3348-342X
  2. Emanuela Santini

    Department of Neuroscience, Karolinska Institutet, Solna, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  3. Robert Sears

    Center for Neural Science, New York University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Zachary Deane

    Department of Physiology and Neurobiology, University of Connecticut, Storrs, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Rahul N Kanadia

    Department of Physiology and Neurobiology, University of Connecticut, Storrs, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Joseph E LeDoux

    Center for Neural Science, New York University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Tenzin Lhakhang

    Applied Bioinformatics Laboratories, New York University School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Aristotelis Tsirigos

    Applied Bioinformatics Laboratories, New York University School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Adriana Heguy

    Genome Technology Center, New York University School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Eric Klann

    Center for Neural Science, New York University, New York, United States
    For correspondence
    ek65@nyu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7379-6802

Funding

National Institute of Neurological Disorders and Stroke (NS034007)

  • Eric Klann

Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD082013)

  • Eric Klann

National Institute of Mental Health (MH083583)

  • Linnaea E Ostroff

National Institute of Neurological Disorders and Stroke (NS047384)

  • Eric Klann

National Institute of Mental Health (MH094965)

  • Linnaea E Ostroff

National Institute of Mental Health (MH119517)

  • Linnaea E Ostroff

National Institute of Neurological Disorders and Stroke (NS087112)

  • Emanuela Santini

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

Ethics

Animal experimentation: All animal procedures were performed in accordance with the guidelines in the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and were approved by the Animal Care and Use Committees of New York University (protocol 01-1097) and the University of Connecticut (protocol A17-036).

Copyright

© 2019, Ostroff 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

  • 4,522
    views
  • 645
    downloads
  • 58
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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. Linnaea E Ostroff
  2. Emanuela Santini
  3. Robert Sears
  4. Zachary Deane
  5. Rahul N Kanadia
  6. Joseph E LeDoux
  7. Tenzin Lhakhang
  8. Aristotelis Tsirigos
  9. Adriana Heguy
  10. Eric Klann
(2019)
Axon TRAP reveals learning-associated alterations in cortical axonal mRNAs in the lateral amgydala
eLife 8:e51607.
https://doi.org/10.7554/eLife.51607

Share this article

https://doi.org/10.7554/eLife.51607

Further reading

    1. Neuroscience
    Sharon Inberg, Yael Iosilevskii ... Benjamin Podbilewicz
    Research Article

    Dendrites are crucial for receiving information into neurons. Sensory experience affects the structure of these tree-like neurites, which, it is assumed, modifies neuronal function, yet the evidence is scarce, and the mechanisms are unknown. To study whether sensory experience affects dendritic morphology, we use the Caenorhabditis elegans' arborized nociceptor PVD neurons, under natural mechanical stimulation induced by physical contacts between individuals. We found that mechanosensory signals induced by conspecifics and by glass beads affect the dendritic structure of the PVD. Moreover, developmentally isolated animals show a decrease in their ability to respond to harsh touch. The structural and behavioral plasticity following sensory deprivation are functionally independent of each other and are mediated by an array of evolutionarily conserved mechanosensory amiloride-sensitive epithelial sodium channels (degenerins). Calcium imaging of the PVD neurons in a micromechanical device revealed that controlled mechanical stimulation of the body wall produces similar calcium dynamics in both isolated and crowded animals. Our genetic results, supported by optogenetic, behavioral, and pharmacological evidence, suggest an activity-dependent homeostatic mechanism for dendritic structural plasticity, that in parallel controls escape response to noxious mechanosensory stimuli.

    1. Neuroscience
    Raven Star Wallace, Bronte Mckeown ... Jonathan Smallwood
    Research Article

    Movie-watching is a central aspect of our lives and an important paradigm for understanding the brain mechanisms behind cognition as it occurs in daily life. Contemporary views of ongoing thought argue that the ability to make sense of events in the ‘here and now’ depend on the neural processing of incoming sensory information by auditory and visual cortex, which are kept in check by systems in association cortex. However, we currently lack an understanding of how patterns of ongoing thoughts map onto the different brain systems when we watch a film, partly because methods of sampling experience disrupt the dynamics of brain activity and the experience of movie-watching. Our study established a novel method for mapping thought patterns onto the brain activity that occurs at different moments of a film, which does not disrupt the time course of brain activity or the movie-watching experience. We found moments when experience sampling highlighted engagement with multi-sensory features of the film or highlighted thoughts with episodic features, regions of sensory cortex were more active and subsequent memory for events in the movie was better—on the other hand, periods of intrusive distraction emerged when activity in regions of association cortex within the frontoparietal system was reduced. These results highlight the critical role sensory systems play in the multi-modal experience of movie-watching and provide evidence for the role of association cortex in reducing distraction when we watch films.