Multi-neuron intracellular recording in vivo via interacting autopatching robots

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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.

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Suhasa B Kodandaramaiah

Media Lab, Massachusetts Institute of Technology, Cambridge, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-7767-2644
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.

"This ORCID iD identifies the author of this article:" 0000-0002-8974-9717
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.
Annabelle C Singer

Media Lab, Massachusetts Institute of Technology, Cambridge, United States

Competing interests
The authors declare that no competing interests exist.
Xue Han

Department of Biomedical Engineering, Boston University, Boston, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-3896-4609
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.
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.
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.

"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.

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.

Copyright

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.