Conditioned respiratory threat in the subdivisions of the human periaqueductal gray

  1. Olivia K Faull  Is a corresponding author
  2. Mark Jenkinson
  3. Martyn Ezra
  4. Kyle T.S Pattinson
  1. University of Oxford, United Kingdom

Abstract

The sensation of breathlessness is the most threatening symptom of respiratory disease. The different subdivisions of the midbrain periaqueductal gray (PAG) are intricately (and differentially) involved in integrating behavioural responses to threat in animals, while the PAG has previously only been considered as a single entity in human research. Here we investigate how these individual PAG columns are differently involved with respiratory threat. Eighteen healthy subjects were conditioned to associate shapes with certain or uncertain impending respiratory load, and scanned the following day during anticipation and application of inspiratory loading using 7 T functional MRI. We showed activity in the ventrolateral PAG (vlPAG) during anticipation of resistive loading, with activity in the lateral PAG (lPAG) during resistive loading, showing spatially and temporally distinct functions within this structure. We propose that lPAG is involved with sensorimotor responses to breathlessness, while the vlPAG operates within the threat perception network for impending breathlessness.

Article and author information

Author details

  1. Olivia K Faull

    Oxford Centre for Functional MRI of the Brain, University of Oxford, Oxford, United Kingdom
    For correspondence
    olivia.faull@ndcn.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  2. Mark Jenkinson

    Oxford Centre for Functional MRI of the Brain, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Martyn Ezra

    Oxford Centre for Functional MRI of the Brain, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Kyle T.S Pattinson

    Oxford Centre for Functional MRI of the Brain, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Human subjects: The Oxfordshire Clinical Research Ethics Committee approved the study and volunteers gave written, informed consent prior to testing.

Reviewing Editor

  1. Jan-Marino Ramirez, Seattle Children's Research Institute and University of Washington, United States

Publication history

  1. Received: October 2, 2015
  2. Accepted: February 26, 2016
  3. Accepted Manuscript published: February 27, 2016 (version 1)
  4. Version of Record published: March 30, 2016 (version 2)
  5. Version of Record updated: April 22, 2016 (version 3)

Copyright

© 2016, Faull 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

  • 1,984
    Page views
  • 347
    Downloads
  • 45
    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. Olivia K Faull
  2. Mark Jenkinson
  3. Martyn Ezra
  4. Kyle T.S Pattinson
(2016)
Conditioned respiratory threat in the subdivisions of the human periaqueductal gray
eLife 5:e12047.
https://doi.org/10.7554/eLife.12047

Further reading

    1. Developmental Biology
    2. Neuroscience
    Mariah L Hoye et al.
    Research Article

    Mutations in the RNA helicase, DDX3X, are a leading cause of Intellectual Disability and present as DDX3X syndrome, a neurodevelopmental disorder associated with cortical malformations and autism. Yet, the cellular and molecular mechanisms by which DDX3X controls cortical development are largely unknown. Here, using a mouse model of Ddx3x loss-of-function we demonstrate that DDX3X directs translational and cell cycle control of neural progenitors, which underlies precise corticogenesis. First, we show brain development is sensitive to Ddx3x dosage; complete Ddx3x loss from neural progenitors causes microcephaly in females, whereas hemizygous males and heterozygous females show reduced neurogenesis without marked microcephaly. In addition, Ddx3x loss is sexually dimorphic, as its paralog, Ddx3y, compensates for Ddx3x in the developing male neocortex. Using live imaging of progenitors, we show that DDX3X promotes neuronal generation by regulating both cell cycle duration and neurogenic divisions. Finally, we use ribosome profiling in vivo to discover the repertoire of translated transcripts in neural progenitors, including those which are DDX3X-dependent and essential for neurogenesis. Our study reveals invaluable new insights into the etiology of DDX3X syndrome, implicating dysregulated progenitor cell cycle dynamics and translation as pathogenic mechanisms.

    1. Neuroscience
    Payel Chatterjee et al.
    Research Article

    During flight maneuvers, insects exhibit compensatory head movements which are essential for stabilizing the visual field on their retina, reducing motion blur, and supporting visual self-motion estimation. In Diptera, such head movements are mediated via visual feedback from their compound eyes that detect retinal slip, as well as rapid mechanosensory feedback from their halteres - the modified hindwings that sense the angular rates of body rotations. Because non-Dipteran insects lack halteres, it is not known if mechanosensory feedback about body rotations plays any role in their head stabilization response. Diverse non-Dipteran insects are known to rely on visual and antennal mechanosensory feedback for flight control. In hawkmoths, for instance, reduction of antennal mechanosensory feedback severely compromises their ability to control flight. Similarly, when the head movements of freely-flying moths are restricted, their flight ability is also severely impaired. The role of compensatory head movements as well as multimodal feedback in insect flight raises an interesting question: in insects that lack halteres, what sensory cues are required for head stabilization? Here, we show that in the nocturnal hawkmoth Daphnis nerii, compensatory head movements are mediated by combined visual and antennal mechanosensory feedback. We subjected tethered moths to open-loop body roll rotations under different lighting conditions, and measured their ability to maintain head angle in the presence or absence of antennal mechanosensory feedback. Our study suggests that head stabilization in moths is mediated primarily by visual feedback during roll movements at lower frequencies, whereas antennal mechanosensory feedback is required when roll occurs at higher frequency. These findings are consistent with the hypothesis that control of head angle results from a multimodal feedback loop that integrates both visual and antennal mechanosensory feedback, albeit at different latencies. At adequate light levels, visual feedback is sufficient for head stabilization primarily at low frequencies of body roll. However, under dark conditions, antennal mechanosensory feedback is essential for the control of head movements at high of body roll.