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

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 "This ORCID iD identifies the author of this article:" 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 "This ORCID iD identifies the author of this article:" 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 "This ORCID iD identifies the author of this article:" 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 "This ORCID iD identifies the author of this article:" 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.

Reviewing Editor

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

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.

Version history

  1. Received: December 24, 2016
  2. Accepted: December 19, 2017
  3. Accepted Manuscript published: January 3, 2018 (version 1)
  4. Version of Record published: February 14, 2018 (version 2)
  5. Version of Record updated: January 16, 2019 (version 3)

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.

Metrics

  • 6,396
    views
  • 814
    downloads
  • 32
    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. 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
  8. Craig R Forest
(2018)
Multi-neuron intracellular recording in vivo via interacting autopatching robots
eLife 7:e24656.
https://doi.org/10.7554/eLife.24656

Share this article

https://doi.org/10.7554/eLife.24656

Further reading

    1. Neuroscience
    Songyao Zhang, Tuo Zhang ... Tianming Liu
    Research Article

    Cortical folding is an important feature of primate brains that plays a crucial role in various cognitive and behavioral processes. Extensive research has revealed both similarities and differences in folding morphology and brain function among primates including macaque and human. The folding morphology is the basis of brain function, making cross-species studies on folding morphology important for understanding brain function and species evolution. However, prior studies on cross-species folding morphology mainly focused on partial regions of the cortex instead of the entire brain. Previously, our research defined a whole-brain landmark based on folding morphology: the gyral peak. It was found to exist stably across individuals and ages in both human and macaque brains. Shared and unique gyral peaks in human and macaque are identified in this study, and their similarities and differences in spatial distribution, anatomical morphology, and functional connectivity were also dicussed.

    1. Neuroscience
    Avani Koparkar, Timothy L Warren ... Lena Veit
    Research Article

    Complex skills like speech and dance are composed of ordered sequences of simpler elements, but the neuronal basis for the syntactic ordering of actions is poorly understood. Birdsong is a learned vocal behavior composed of syntactically ordered syllables, controlled in part by the songbird premotor nucleus HVC (proper name). Here, we test whether one of HVC’s recurrent inputs, mMAN (medial magnocellular nucleus of the anterior nidopallium), contributes to sequencing in adult male Bengalese finches (Lonchura striata domestica). Bengalese finch song includes several patterns: (1) chunks, comprising stereotyped syllable sequences; (2) branch points, where a given syllable can be followed probabilistically by multiple syllables; and (3) repeat phrases, where individual syllables are repeated variable numbers of times. We found that following bilateral lesions of mMAN, acoustic structure of syllables remained largely intact, but sequencing became more variable, as evidenced by ‘breaks’ in previously stereotyped chunks, increased uncertainty at branch points, and increased variability in repeat numbers. Our results show that mMAN contributes to the variable sequencing of vocal elements in Bengalese finch song and demonstrate the influence of recurrent projections to HVC. Furthermore, they highlight the utility of species with complex syntax in investigating neuronal control of ordered sequences.