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Multi-neuron intracellular recording in vivo via interacting autopatching robots

  1. Suhasa B Kodandaramaiah
  2. Francisco J Flores
  3. Gregory L Holst
  4. Annabelle C Singer
  5. Xue Han
  6. Emery N Brown
  7. Edward S Boyden Is a corresponding author
  8. Craig R Forest Is a corresponding author
  1. Massachusetts Institute of Technology, United States
  2. Massachusetts General Hospital, United States
  3. Georgia Institute of Technology, United States
  4. Boston University, United States
  5. University of Minnesota, United States
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Cite as: eLife 2018;7:e24656 doi: 10.7554/eLife.24656

Abstract

The activities of groups of neurons in a circuit or brain region are important for neuronal computations that contribute to behaviors and disease states. Traditional extracellular recordings have been powerful and scalable, but much less is known about the intracellular processes that lead to spiking activity. We present a robotic system, the multipatcher, capable of automatically obtaining blind whole-cell patch clamp recordings from multiple neurons simultaneously. The multipatcher significantly extends automated patch clamping, or 'autopatching', to guide four interacting electrodes in a coordinated fashion, avoiding mechanical coupling in the brain. We demonstrate its performance in the cortex of anesthetized and awake mice. A multipatcher with four electrodes took an average of 10 min to obtain dual or triple recordings in 29% of trials in anesthetized mice, and in 18% of the trials in awake mice, thus illustrating practical yield and throughput to obtain multiple, simultaneous whole-cell recordings in vivo.

Article and author information

Author details

  1. Suhasa B Kodandaramaiah

    Media Lab, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0002-7767-2644
  2. Francisco J Flores

    Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0002-8974-9717
  3. Gregory L Holst

    G.W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Annabelle C Singer

    Media Lab, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Xue Han

    Department of Biomedical Engineering, Boston University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0003-3896-4609
  6. Emery N Brown

    Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Edward S Boyden

    Media Lab, Massachusetts Institute of Technology, Cambridge, United States
    For correspondence
    esb@media.mit.edu
    Competing interests
    The authors declare that no competing interests exist.
  8. Craig R Forest

    Department of Mechanical Engineering, University of Minnesota, Minneapolis, United States
    For correspondence
    cforest@gatech.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0001-5343-1769

Funding

New York Stem Cell Foundation

  • Edward S Boyden

McGovern Institute Neurotechnology Fund

  • Suhasa B Kodandaramaiah

National Institutes of Health

  • Gregory L Holst

National Science Foundation

  • Edward S Boyden

National Institutes of Health (R01 EY023173)

  • Craig R Forest

National Institutes of Health (R01-GM104948)

  • Emery N Brown

National Institutes of Health (P01-GM118620)

  • Emery N Brown

Massachusetts General Hospital

  • Emery N Brown

Picower Institue for Learning and Memory

  • Emery N Brown

National Institutes of Health (1R21NS103098-01)

  • Suhasa B Kodandaramaiah

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

Ethics

Animal experimentation: We conducted all animal work in accordance to federal, state, and local regulations, and following NIH and AAALAC guidelines and standards. The corresponding protocol (#0113-008-16) was approved by the Institutional Committee on Animal Care at the Massachusetts Institute of Technology.

Reviewing Editor

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

Publication history

  1. Received: December 24, 2016
  2. Accepted: December 19, 2017
  3. Accepted Manuscript published: January 3, 2018 (version 1)

Copyright

© 2018, Kodandaramaiah 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.

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