1. Neuroscience
Download icon

Automated task training and longitudinal monitoring of mouse mesoscale cortical circuits using home cages

  1. Timothy H Murphy  Is a corresponding author
  2. Nicholas J Michelson
  3. Jamie D Boyd
  4. Tony Fong
  5. Luis A Bolanos
  6. David Bierbrauer
  7. Teri Siu
  8. Matilde Balbi
  9. Federico Bolanos
  10. Matthieu Vanni
  11. Jeff M LeDue
  1. University of British Columbia, Canada
  2. University of Britsih Columbia, Canada
Tools and Resources
  • Cited 4
  • Views 3,243
  • Annotations
Cite this article as: eLife 2020;9:e55964 doi: 10.7554/eLife.55964

Abstract

We report improved automated open-source methodology for head-fixed mesoscale cortical imaging and/or behavioral training of home cage mice using Raspberry Pi-based hardware. Staged partial and probabilistic restraint allows mice to adjust to self-initiated headfixation over 3 weeks' time with ~50% participation rate. We support a cue-based behavioral licking task monitored by a capacitive touch-sensor water spout. While automatically head-fixed, we acquire spontaneous, movement-triggered, or licking task-evoked GCaMP6 cortical signals. An analysis pipeline marked both behavioral events, as well as analyzed brain fluorescence signals as they relate to spontaneous and/or task-evoked behavioral activity. Mice were trained to suppress licking and wait for cues that marked the delivery of water. Correct rewarded go-trials were associated with widespread activation of midline and lateral barrel cortex areas following a vibration cue and delayed frontal and lateral motor cortex activation. Cortical GCaMP signals predicted trial success and correlated strongly with trial-outcome dependent body movements.

Data availability

The name of each brain imaging file which contains both the mouse ID and the time stamp can be found in the SQL database (RFIDtag_xxxx_timestamp.raw; see Methods for URL and hosted as a full text file archive on Zenodo (https://doi.org/10.5281/zenodo.3268838) for the 5 cages of male mice that compose figures 1-7 and cage 6 female mice https://doi.org/10.5683/SP2/9RFXRP.All text file behavioral data is included online as well as image data for figures 8 and supplemental figure 2 are found on https://doi.org/10.5281/zenodo.3243572, all data files and code for figures 9 and 10 are found in https://doi.org/10.5683/SP2/ZTOPUM and female mouse behavioral data https://doi.org/10.5683/SP2/9RFXRP. All Python data acquisition code can be found on https://github.com/jamieboyd/AutoHeadFix/ and https://github.com/ubcbraincircuits/AutoHeadFix.

The following data sets were generated

Article and author information

Author details

  1. Timothy H Murphy

    Department of Psychiatry, Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    For correspondence
    thmurphy@mail.ubc.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0093-4490

  2. Nicholas J Michelson

    Department of Psychiatry, Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.

  3. Jamie D Boyd

    Department of Psychiatry, Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.

  4. Tony Fong

    Department of Psychiatry, Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.

  5. Luis A Bolanos

    Department of Psychiatry, Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.

  6. David Bierbrauer

    Department of Psychiatry, Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.

  7. Teri Siu

    Department of Psychiatry, Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.

  8. Matilde Balbi

    Department of Psychiatry, Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.

  9. Federico Bolanos

    Department of Psychiatry, Kinsmen Laboratory of Neurological Research, University of Britsih Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.

  10. Matthieu Vanni

    Department of Psychiatry, Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.

  11. Jeff M LeDue

    Department of Psychiatry, Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.

Funding

Canadian Institutes of Health Research (FDN-143209)

  • Timothy H Murphy

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 procedures were conducted with approval from the University of British Columbia Animal Care Committee and in accordance with guidelines set forth by the Canadian Council for Animal Care.

Reviewing Editor

  1. David Kleinfeld, University of California, San Diego, United States

Publication history

  1. Received: February 12, 2020
  2. Accepted: May 7, 2020
  3. Accepted Manuscript published: May 15, 2020 (version 1)
  4. Version of Record published: July 2, 2020 (version 2)

Copyright

© 2020, Murphy 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

  • 3,243
    Page views
  • 400
    Downloads
  • 4
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

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)

Categories and tags

Research organism

Further reading

    1. Neuroscience

    Control of neurotransmitter release by two distinct membrane-binding faces of the Munc13-1 C1C2B region

    Marcial Camacho et al.
    Research Article Updated

    Munc13-1 plays a central role in neurotransmitter release through its conserved C-terminal region, which includes a diacyglycerol (DAG)-binding C1 domain, a Ca2+/PIP2-binding C2B domain, a MUN domain and a C2C domain. Munc13-1 was proposed to bridge synaptic vesicles to the plasma membrane through distinct interactions of the C1C2B region with the plasma membrane: (i) one involving a polybasic face that is expected to yield a perpendicular orientation of Munc13-1 and hinder release; and (ii) another involving the DAG-Ca2+-PIP2-binding face that is predicted to result in a slanted orientation and facilitate release. Here, we have tested this model and investigated the role of the C1C2B region in neurotransmitter release. We find that K603E or R769E point mutations in the polybasic face severely impair Ca2+-independent liposome bridging and fusion in in vitro reconstitution assays, and synaptic vesicle priming in primary murine hippocampal cultures. A K720E mutation in the polybasic face and a K706E mutation in the C2B domain Ca2+-binding loops have milder effects in reconstitution assays and do not affect vesicle priming, but enhance or impair Ca2+-evoked release, respectively. The phenotypes caused by combining these mutations are dominated by the K603E and R769E mutations. Our results show that the C1-C2B region of Munc13-1 plays a central role in vesicle priming and support the notion that two distinct faces of this region control neurotransmitter release and short-term presynaptic plasticity.

    1. Biochemistry and Chemical Biology
    2. Neuroscience

    Neurotoxin-mediated ­­potent activation of the axon degeneration regulator SARM1

    Andrea Loreto et al.
    Research Article

    Axon loss underlies symptom onset and progression in many neurodegenerative disorders. Axon degeneration in injury and disease is promoted by activation of the nicotinamide adenine dinucleotide (NAD)-consuming enzyme SARM1. Here, we report a novel activator of SARM1, a metabolite of the pesticide and neurotoxin vacor. Removal of SARM1 completely rescues mouse neurons from vacor-induced neuron and axon death in vitro and in vivo. We present the crystal structure the Drosophila SARM1 regulatory domain complexed with this activator, the vacor metabolite VMN, which as the most potent activator yet know is likely to support drug development for human SARM1 and NMNAT2 disorders. This study indicates the mechanism of neurotoxicity and pesticide action by vacor, raises important questions about other pyridines in wider use today, provides important new tools for drug discovery, and demonstrates that removing SARM1 can robustly block programmed axon death induced by toxicity as well as genetic mutation.

    1. Neuroscience

    Maturation of persistent and hyperpolarization-activated inward currents shapes the differential activation of motoneuron subtypes during postnatal development

    Simon A Sharples, Gareth B Miles
    Research Article Updated

    The size principle underlies the orderly recruitment of motor units; however, motoneuron size is a poor predictor of recruitment amongst functionally defined motoneuron subtypes. Whilst intrinsic properties are key regulators of motoneuron recruitment, the underlying currents involved are not well defined. Whole-cell patch-clamp electrophysiology was deployed to study intrinsic properties, and the underlying currents, that contribute to the differential activation of delayed and immediate firing motoneuron subtypes. Motoneurons were studied during the first three postnatal weeks in mice to identify key properties that contribute to rheobase and may be important to establish orderly recruitment. We find that delayed and immediate firing motoneurons are functionally homogeneous during the first postnatal week and are activated based on size, irrespective of subtype. The rheobase of motoneuron subtypes becomes staggered during the second postnatal week, which coincides with the differential maturation of passive and active properties, particularly persistent inward currents. Rheobase of delayed firing motoneurons increases further in the third postnatal week due to the development of a prominent resting hyperpolarization-activated inward current. Our results suggest that motoneuron recruitment is multifactorial, with recruitment order established during postnatal development through the differential maturation of passive properties and sequential integration of persistent and hyperpolarization-activated inward currents.