1. Neuroscience
Download icon

Motoneurons regulate the central pattern generator during drug-induced locomotor-like activity in the neonatal mouse

  1. Melanie Falgairolle  Is a corresponding author
  2. Joshua G Puhl
  3. Avinash Pujala
  4. Wenfang Liu
  5. Michael James O'Donovan
  1. National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States
  2. University of Minnesota, United States
  3. Howard Hughes Medical Institute, United States
Research Article
  • Cited 27
  • Views 1,897
  • Annotations
Cite this article as: eLife 2017;6:e26622 doi: 10.7554/eLife.26622

Abstract

Motoneurons are traditionally viewed as the output of the spinal cord that do not influence locomotor rhythmogenesis. We assessed the role of motoneuron firing during ongoing locomotor-like activity in neonatal mice expressing archaerhopsin-3 (Arch), halorhodopsin (eNpHR), or channelrhodopsin-2 (ChR2) in Choline acetyltransferase expressing neurons (ChAT+) or the LIM-homeodomain transcription factor Isl1+ neurons. Illumination of the lumbar cord in mice expressing eNpHR or Arch in ChAT+ or Isl1+ neurons, depressed motoneuron discharge, transiently decreased the frequency, and perturbed the phasing of the locomotor-like rhythm. When the light was turned off motoneuron firing and locomotor frequency both transiently increased. These effects were not due to cholinergic neurotransmission, persisted during partial blockade of gap junctions and were mediated, in part, by AMPAergic transmission. In spinal cords expressing ChR2, illumination increased motoneuron discharge and transiently accelerated the rhythm. We conclude that motoneurons provide feedback to the central pattern generator (CPG) during drug-induced locomotor-like activity.

Article and author information

Author details

  1. Melanie Falgairolle

    Developmental Neurobiology section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States
    For correspondence
    melanie.falgairolle@nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5243-4714
  2. Joshua G Puhl

    Department of Entomology, University of Minnesota, Saint Paul, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Avinash Pujala

    Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Wenfang Liu

    Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Michael James O'Donovan

    Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2487-7547

Funding

National Institutes of Health (NINDS Intramural program)

  • Melanie Falgairolle

National Institutes of Health (NINDS Intramural program)

  • Michael James O'Donovan

National Institutes of Health (NINDS Intramural program)

  • Joshua G Puhl

National Institutes of Health (NINDS Intramural NRSA)

  • Joshua G Puhl

National Institutes of Health (NINDS Intramural program)

  • Wenfang Liu

National Institutes of Health (NINDS Intramural program)

  • Avinash Pujala

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 experiments were carried out in compliance with the National Institutes of Neurological Disorders and Stroke Animal Care and Use Committee (Animal Protocol Number 1267-12 and 1267-15).

Reviewing Editor

  1. Ole Kiehn, Karolinska Institutet, Sweden

Publication history

  1. Received: March 9, 2017
  2. Accepted: June 30, 2017
  3. Accepted Manuscript published: July 3, 2017 (version 1)
  4. Version of Record published: August 9, 2017 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Metrics

  • 1,897
    Page views
  • 330
    Downloads
  • 27
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, 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)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Biochemistry and Chemical Biology
    2. Neuroscience
    Ricardo M Santos, Anton Sirota
    Research Article Updated

    Cholinergic fast time-scale modulation of cortical physiology is critical for cognition, but direct local measurement of neuromodulators in vivo is challenging. Choline oxidase (ChOx)-based electrochemical biosensors have been used to capture fast cholinergic signals in behaving animals. However, these transients might be biased by local field potential and O2-evoked enzymatic responses. Using a novel Tetrode-based Amperometric ChOx (TACO) sensor, we performed highly sensitive and selective simultaneous measurement of ChOx activity (COA) and O2. In vitro and in vivo experiments, supported by mathematical modeling, revealed that non-steady-state enzyme responses to O2 give rise to phasic COA dynamics. This mechanism accounts for most of COA transients in the hippocampus, including those following locomotion bouts and sharp-wave/ripples. Our results suggest that it is unfeasible to probe phasic cholinergic signals under most behavioral paradigms with current ChOx biosensors. This confound is generalizable to any oxidase-based biosensor, entailing rigorous controls and new biosensor designs.

    1. Neuroscience
    Nina Rouhani, Yael Niv
    Research Article

    Memory helps guide behavior, but which experiences from the past are prioritized? Classic models of learning posit that events associated with unpredictable outcomes as well as, paradoxically, predictable outcomes, deploy more attention and learning for those events. Here, we test reinforcement learning and subsequent memory for those events, and treat signed and unsigned reward prediction errors (RPEs), experienced at the reward-predictive cue or reward outcome, as drivers of these two seemingly contradictory signals. By fitting reinforcement learning models to behavior, we find that both RPEs contribute to learning by modulating a dynamically changing learning rate. We further characterize the effects of these RPE signals on memory, and show that both signed and unsigned RPEs enhance memory, in line with midbrain dopamine and locus-coeruleus modulation of hippocampal plasticity, thereby reconciling separate findings in the literature.