Automated long-term recording and analysis of neural activity in behaving animals

Abstract

Addressing how neural circuits underlie behavior is routinely done by measuring electrical activity from single neurons in experimental sessions. While such recordings yield snapshots of neural dynamics during specified tasks, they are ill-suited for tracking single-unit activity over longer timescales relevant for most developmental and learning processes, or for capturing neural dynamics across different behavioral states. Here we describe an automated platform for continuous long-term recordings of neural activity and behavior in freely moving rodents. An unsupervised algorithm identifies and tracks the activity of single units over weeks of recording, dramatically simplifying the analysis of large datasets. Months-long recordings from motor cortex and striatum made and analyzed with our system revealed remarkable stability in basic neuronal properties, such as firing rates and inter-spike interval distributions. Interneuronal correlations and the representation of different movements and behaviors were similarly stable. This establishes the feasibility of high-throughput long-term extracellular recordings in behaving animals.

Data availability

The following data sets were generated

Article and author information

Author details

  1. Ashesh K Dhawale

    Department of Organismic and Evolutionary Biology and Center for Brain Science, 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:" 0000-0001-7438-1115
  2. Rajesh Poddar

    Department of Organismic and Evolutionary Biology and Center for Brain Science, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Steffen BE Wolff

    Department of Organismic and Evolutionary Biology and Center for Brain Science, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Valentin A Normand

    Department of Organismic and Evolutionary Biology and Center for Brain Science, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Evi Kopelowitz

    Department of Organismic and Evolutionary Biology and Center for Brain Science, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Bence P Ölveczky

    Department of Organismic and Evolutionary Biology and Center for Brain Science, Harvard University, Cambridge, United States
    For correspondence
    olveczky@fas.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2499-2705

Funding

Star Family Challenge Award

  • Bence P Ölveczky

Human Frontier Science Program

  • Steffen B.E Wolff

Life Sciences Research Foundation

  • Ashesh K Dhawale

Charles A. King Trust

  • Ashesh K Dhawale

National Institute of Neurological Disorders and Stroke (R01 NS099323-02)

  • Bence P Ölveczky

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#29-15) of the Harvard University. All surgery was performed under isoflurane anesthesia, and every effort was made to minimize suffering.

Reviewing Editor

  1. Andrew J King, University of Oxford, United Kingdom

Publication history

  1. Received: April 11, 2017
  2. Accepted: August 24, 2017
  3. Accepted Manuscript published: September 8, 2017 (version 1)
  4. Version of Record published: September 28, 2017 (version 2)

Copyright

© 2017, Dhawale 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

  • 7,864
    Page views
  • 1,307
    Downloads
  • 60
    Citations

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

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. Ashesh K Dhawale
  2. Rajesh Poddar
  3. Steffen BE Wolff
  4. Valentin A Normand
  5. Evi Kopelowitz
  6. Bence P Ölveczky
(2017)
Automated long-term recording and analysis of neural activity in behaving animals
eLife 6:e27702.
https://doi.org/10.7554/eLife.27702

Further reading

    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.

    1. Developmental Biology
    2. Neuroscience
    Ashtyn T Wiltbank et al.
    Research Article

    Efficient neurotransmission is essential for organism survival and is enhanced by myelination. However, the genes that regulate myelin and myelinating glial cell development have not been fully characterized. Data from our lab and others demonstrates that cd59, which encodes for a small GPI-anchored glycoprotein, is highly expressed in developing zebrafish, rodent, and human oligodendrocytes (OLs) and Schwann cells (SCs), and that patients with CD59 dysfunction develop neurological dysfunction during early childhood. Yet, the function of Cd59 in the developing nervous system is currently undefined. In this study, we demonstrate that cd59 is expressed in a subset of developing SCs. Using cd59 mutant zebrafish, we show that developing SCs proliferate excessively and nerves may have reduced myelin volume, altered myelin ultrastructure, and perturbed node of Ranvier assembly. Finally, we demonstrate that complement activity is elevated in cd59 mutants and that inhibiting inflammation restores SC proliferation, myelin volume, and nodes of Ranvier to wildtype levels. Together, this work identifies Cd59 and developmental inflammation as key players in myelinating glial cell development, highlighting the collaboration between glia and the innate immune system to ensure normal neural development.