A Toll-receptor map underlies structural brain plasticity

  1. Guiyi Li
  2. Manuel G Forero
  3. Jill S Wentzell
  4. Ilgim Durmus
  5. Reinhard Wolf
  6. Niki C Anthoney
  7. Mieczyslaw Parker
  8. Ruiying Jiang
  9. Jacob Hasenauer
  10. Nicholas James Strausfeld
  11. Martin Heisenberg
  12. Alicia Hidalgo  Is a corresponding author
  1. University of Birmingham, United Kingdom
  2. Universidad de Ibagué, Colombia
  3. University of Würzburg, Germany
  4. University of Arizona, United States

Abstract

Experience alters brain structure, but the underlying mechanism remained unknown. Structural plasticity reveals that brain function is encoded in generative changes to cells that compete with destructive processes driving neurodegeneration. At an adult critical period, experience increases fiber number and brain size in Drosophila. Here, we asked if Toll receptors are involved. Tolls demarcate a map of brain anatomical domains. Focusing on Toll-2, loss of function caused apoptosis, neurite atrophy and impaired behaviour. Toll-2 gain of function and neuronal activity at the critical period increased cell number. Toll-2 induced cycling of adult progenitor cells via a novel pathway, that antagonized MyD88-dependent quiescence, and engaged Weckle and Yorkie downstream. Constant knock-down of multiple Tolls synergistically reduced brain size. Conditional over-expression of Toll-2 and wek at the adult critical period increased brain size. Through their topographic distribution, Toll receptors regulate neuronal number and brain size, modulating structural plasticity in the adult brain.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Guiyi Li

    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Manuel G Forero

    Facultad de Ingeniería, Universidad de Ibagué, Ibagué, Colombia
    Competing interests
    The authors declare that no competing interests exist.
  3. Jill S Wentzell

    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Ilgim Durmus

    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Reinhard Wolf

    Rudolf-Virchow-Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Niki C Anthoney

    Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3311-6328
  7. Mieczyslaw Parker

    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Ruiying Jiang

    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Jacob Hasenauer

    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Nicholas James Strausfeld

    Department of Neuroscience, University of Arizona, Tucson, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1115-1774
  11. Martin Heisenberg

    Rudolf-Virchow-Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4462-8655
  12. Alicia Hidalgo

    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    For correspondence
    a.hidalgo@bham.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8041-5764

Funding

Biotechnology and Biological Sciences Research Council (BB/P004997/1)

  • Alicia Hidalgo

Biotechnology and Biological Sciences Research Council (BB/R017034/1)

  • Alicia Hidalgo

EU Marie Curie-Sklodowska Fellowship (NPN)

  • Jill S Wentzell

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

Reviewing Editor

  1. Hugo J Bellen, Baylor College of Medicine, United States

Version history

  1. Received: October 14, 2019
  2. Accepted: February 12, 2020
  3. Accepted Manuscript published: February 18, 2020 (version 1)
  4. Version of Record published: March 17, 2020 (version 2)

Copyright

© 2020, Li 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

  • 4,438
    views
  • 706
    downloads
  • 32
    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. Guiyi Li
  2. Manuel G Forero
  3. Jill S Wentzell
  4. Ilgim Durmus
  5. Reinhard Wolf
  6. Niki C Anthoney
  7. Mieczyslaw Parker
  8. Ruiying Jiang
  9. Jacob Hasenauer
  10. Nicholas James Strausfeld
  11. Martin Heisenberg
  12. Alicia Hidalgo
(2020)
A Toll-receptor map underlies structural brain plasticity
eLife 9:e52743.
https://doi.org/10.7554/eLife.52743

Share this article

https://doi.org/10.7554/eLife.52743

Further reading

    1. Neuroscience
    Daniel Hoops, Robert Kyne ... Cecilia Flores
    Short Report

    Dopamine axons are the only axons known to grow during adolescence. Here, using rodent models, we examined how two proteins, Netrin-1 and its receptor, UNC5C, guide dopamine axons toward the prefrontal cortex and shape behaviour. We demonstrate in mice (Mus musculus) that dopamine axons reach the cortex through a transient gradient of Netrin-1-expressing cells – disrupting this gradient reroutes axons away from their target. Using a seasonal model (Siberian hamsters; Phodopus sungorus) we find that mesocortical dopamine development can be regulated by a natural environmental cue (daylength) in a sexually dimorphic manner – delayed in males, but advanced in females. The timings of dopamine axon growth and UNC5C expression are always phase-locked. Adolescence is an ill-defined, transitional period; we pinpoint neurodevelopmental markers underlying this period.

    1. Neuroscience
    Baba Yogesh, Georg B Keller
    Research Article

    Acetylcholine is released in visual cortex by axonal projections from the basal forebrain. The signals conveyed by these projections and their computational significance are still unclear. Using two-photon calcium imaging in behaving mice, we show that basal forebrain cholinergic axons in the mouse visual cortex provide a binary locomotion state signal. In these axons, we found no evidence of responses to visual stimuli or visuomotor prediction errors. While optogenetic activation of cholinergic axons in visual cortex in isolation did not drive local neuronal activity, when paired with visuomotor stimuli, it resulted in layer-specific increases of neuronal activity. Responses in layer 5 neurons to both top-down and bottom-up inputs were increased in amplitude and decreased in latency, whereas those in layer 2/3 neurons remained unchanged. Using opto- and chemogenetic manipulations of cholinergic activity, we found acetylcholine to underlie the locomotion-associated decorrelation of activity between neurons in both layer 2/3 and layer 5. Our results suggest that acetylcholine augments the responsiveness of layer 5 neurons to inputs from outside of the local network, possibly enabling faster switching between internal representations during locomotion.