Dbx1 precursor cells are a source of inspiratory XII premotoneurons

  1. Ann L Revill
  2. Nikolas C Vann
  3. Victoria T Akins
  4. Andrew Kottick
  5. Paul A Gray
  6. Christopher A Del Negro
  7. Gregory D Funk  Is a corresponding author
  1. University of Alberta, Canada
  2. The College of William and Mary, United States
  3. Washington University School of Medicine, United States

Abstract

All behaviors require coordinated activation of motoneurons from central command and premotor networks. The genetic identities of premotoneurons providing behaviorally relevant excitation to any pool of mammalian motoneurons remain unknown. Recently we established in vitro that Dbx1-derived preBötzinger complex neurons are critical for rhythm generation and that a subpopulation serves a premotor function (Wang et al., 2014). Here we further show that a subpopulation of Dbx1-derived intermediate reticular (IRt) neurons are rhythmically active during inspiration and project to the hypoglossal (XII) nucleus that contains motoneurons important for maintaining airway patency. Laser ablation of Dbx1 IRt neurons, 57% of which are glutamatergic, decreased ipsilateral inspiratory motor output without affecting frequency. We conclude that a subset of Dbx1 IRt neurons is a source of premotor excitatory drive, contributing to the inspiratory behavior of XII motoneurons, as well as a key component of the airway control network whose dysfunction contributes to sleep apnea.

Article and author information

Author details

  1. Ann L Revill

    Departments of Physiology, Neuroscience and Mental Health Institute, Women and Children's Health Research Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Nikolas C Vann

    Department of Applied Science, The College of William and Mary, Williamsburg, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Victoria T Akins

    Department of Applied Science, The College of William and Mary, Williamsburg, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Andrew Kottick

    Department of Applied Science, The College of William and Mary, Williamsburg, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Paul A Gray

    Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Christopher A Del Negro

    Department of Applied Science, The College of William and Mary, Williamsburg, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Gregory D Funk

    Departments of Physiology, Neuroscience and Mental Health Institute, Women and Children's Health Research Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
    For correspondence
    gf@ualberta.ca
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: Ethics Statement: All experiments were performed in accordance with guidelines laid down by the NIH in the US regarding the care and use of animals for experimental procedures, the Institute for Laboratory Animal Research, and in compliance with protocols approved by the College of William & Mary Institutional Animal Care and Use Committee (protocol #8828), the Animal Studies Committee at Washington University School of Medicine (protocol #20110249) and the University of Alberta of Medicine Animal Welfare Committee (protocol #255).

Copyright

© 2015, Revill 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

  • 1,104
    views
  • 287
    downloads
  • 50
    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. Ann L Revill
  2. Nikolas C Vann
  3. Victoria T Akins
  4. Andrew Kottick
  5. Paul A Gray
  6. Christopher A Del Negro
  7. Gregory D Funk
(2015)
Dbx1 precursor cells are a source of inspiratory XII premotoneurons
eLife 4:e12301.
https://doi.org/10.7554/eLife.12301

Share this article

https://doi.org/10.7554/eLife.12301

Further reading

    1. Neuroscience
    Gyeong Hee Pyeon, Hyewon Cho ... Yong Sang Jo
    Research Article Updated

    Recent studies suggest that calcitonin gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) represent aversive information and signal a general alarm to the forebrain. If CGRP neurons serve as a true general alarm, their activation would modulate both passive nad active defensive behaviors depending on the magnitude and context of the threat. However, most prior research has focused on the role of CGRP neurons in passive freezing responses, with limited exploration of their involvement in active defensive behaviors. To address this, we examined the role of CGRP neurons in active defensive behavior using a predator-like robot programmed to chase mice. Our electrophysiological results revealed that CGRP neurons encode the intensity of aversive stimuli through variations in firing durations and amplitudes. Optogenetic activation of CGRP neurons during robot chasing elevated flight responses in both conditioning and retention tests, presumably by amplifying the perception of the threat as more imminent and dangerous. In contrast, animals with inactivated CGRP neurons exhibited reduced flight responses, even when the robot was programmed to appear highly threatening during conditioning. These findings expand the understanding of CGRP neurons in the PBN as a critical alarm system, capable of dynamically regulating active defensive behaviors by amplifying threat perception, and ensuring adaptive responses to varying levels of danger.

    1. Neuroscience
    Li Shen, Shuo Li ... Yi Jiang
    Research Article

    When observing others’ behaviors, we continuously integrate their movements with the corresponding sounds to enhance perception and develop adaptive responses. However, how the human brain integrates these complex audiovisual cues based on their natural temporal correspondence remains unclear. Using electroencephalogram (EEG), we demonstrated that rhythmic cortical activity tracked the hierarchical rhythmic structures in audiovisually congruent human walking movements and footstep sounds. Remarkably, the cortical tracking effects exhibit distinct multisensory integration modes at two temporal scales: an additive mode in a lower-order, narrower temporal integration window (step cycle) and a super-additive enhancement in a higher-order, broader temporal window (gait cycle). Furthermore, while neural responses at the lower-order timescale reflect a domain-general audiovisual integration process, cortical tracking at the higher-order timescale is exclusively engaged in the integration of biological motion cues. In addition, only this higher-order, domain-specific cortical tracking effect correlates with individuals’ autistic traits, highlighting its potential as a neural marker for autism spectrum disorder. These findings unveil the multifaceted mechanism whereby rhythmic cortical activity supports the multisensory integration of human motion, shedding light on how neural coding of hierarchical temporal structures orchestrates the processing of complex, natural stimuli across multiple timescales.