1. Genetics and Genomics
  2. Neuroscience

Neural mechanisms of parasite-induced summiting behavior in 'zombie' Drosophila

  1. Carolyn Elya  Is a corresponding author
  2. Danylo Lavrentovich
  3. Emily Lee
  4. Cassandra Pasadyn
  5. Jasper Duval
  6. Maya Basak
  7. Valerie Saykina
  8. Benjamin L de Bivort  Is a corresponding author
  1. Harvard University, United States
https://doi.org/10.7554/eLife.85410
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Cite this article
  1. Carolyn Elya
  2. Danylo Lavrentovich
  3. Emily Lee
  4. Cassandra Pasadyn
  5. Jasper Duval
  6. Maya Basak
  7. Valerie Saykina
  8. Benjamin L de Bivort
(2023)
Neural mechanisms of parasite-induced summiting behavior in 'zombie' Drosophila
eLife 12:e85410.
https://doi.org/10.7554/eLife.85410
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Abstract

For at least two centuries, scientists have been enthralled by the 'zombie' behaviors induced by mind-controlling parasites. Despite this interest, the mechanistic bases of these uncanny processes have remained mostly a mystery. Here, we leverage the recently established Entomophthora muscae-Drosophila melanogaster 'zombie fly' system to reveal the molecular and cellular underpinnings of summit disease, a manipulated behavior evoked by many fungal parasites. Using a new, high-throughput behavior assay to measure summiting, we discovered that summiting behavior is characterized by a burst of locomotion and requires the host circadian and neurosecretory systems, specifically DN1p circadian neurons, pars intercerebralis to corpora allata projecting (PI-CA) neurons and corpora allata (CA), who are solely responsible for juvenile hormone (JH) synthesis and release. Summiting is a fleeting phenomenon, posing a challenge for physiological and biochemical experiments requiring tissue from summiting flies. We addressed this with a machine learning classifier to identify summiting animals in real time. PI-CA neurons and CA appear to be intact in summiting animals, despite E. muscae cells invading the host brain, particularly in the superior medial protocerebrum (SMP), the neuropil that contains DN1p axons and PI-CA dendrites. The blood-brain barrier of flies late in their infection was significantly permeabilized, suggesting that factors in the hemolymph may have greater access to the central nervous system during summiting. Metabolomic analysis of hemolymph from summiting flies revealed differential abundance of several compounds compared to non-summiting flies. Transfusing the hemolymph of summiting flies into non-summiting recipients induced a burst of locomotion, demonstrating that factor(s) in the hemolymph likely cause summiting behavior. Altogether, our work reveals a neuro-mechanistic model for summiting wherein fungal cells perturb the fly's hemolymph, activating the neurohormonal pathway linking clock neurons to juvenile hormone production in the CA, ultimately inducing locomotor activity in their host.

Data availability

Data supporting these results and the analysis code are available at http://lab.debivort.org/zombie-summiting/ and https://doi.org/10.5281/zenodo.7464925. All raw behavioral tracking (centroid versus time) data are available via Harvard Dataverse at https://doi.org/10.7910/DVN/LTMCFR.

The following data sets were generated

Article and author information

Author details

  1. Carolyn Elya

    Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, United States
    For correspondence
    cnelya@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9634-0303

  2. Danylo Lavrentovich

    Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8432-9596

  3. Emily Lee

    Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Cassandra Pasadyn

    Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Jasper Duval

    Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Maya Basak

    Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Valerie Saykina

    Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Benjamin L de Bivort

    Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, United States
    For correspondence
    debivort@oeb.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6165-7696

Funding

Howard Hughes Medical Institute (GT11087)

  • Carolyn Elya

Harvard Quantitative Biology Initiative

  • Danylo Lavrentovich

Alfred P. Sloan Foundation (Research Fellowship)

  • Benjamin L de Bivort

Esther A. and Joseph Klingenstein Fund (Klingenstein-Simons Fellowship Award)

  • Benjamin L de Bivort

Richard and Susan Smith Family Foundation (Odyssey Award)

  • Benjamin L de Bivort

Harvard/MIT (Basic Neuroscience Grant)

  • Benjamin L de Bivort

National Science Foundation (IOS-1557913)

  • Benjamin L de Bivort

National Institute of Neurological Disorders and Stroke (1R01NS121874-01)

  • Benjamin L de Bivort

NSF-Simons Center for Mathematical and Statistical Analysis of Biology (1764269)

  • Danylo Lavrentovich

Harvard Mind Brain and Behavior Initiative (Postdoctoral Fellow Award)

  • Carolyn Elya

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

Reviewing Editor

  1. Sonia Sen, Tata Institute for Genetics and Society, India

Publication history

  1. Received: December 6, 2022
  2. Accepted: May 14, 2023
  3. Accepted Manuscript published: May 15, 2023 (version 1)

Copyright

© 2023, Elya 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.

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  1. Carolyn Elya
  2. Danylo Lavrentovich
  3. Emily Lee
  4. Cassandra Pasadyn
  5. Jasper Duval
  6. Maya Basak
  7. Valerie Saykina
  8. Benjamin L de Bivort
(2023)
Neural mechanisms of parasite-induced summiting behavior in 'zombie' Drosophila
eLife 12:e85410.
https://doi.org/10.7554/eLife.85410

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