High-throughput microcircuit analysis of individual human brains through next-generation multineuron patch-clamp

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Abstract

Comparing neuronal microcircuits across different brain regions, species and individuals can reveal common and divergent principles of network computation. Simultaneous patch-clamp recordings from multiple neurons offer the highest temporal and subthreshold resolution to analyse local synaptic connectivity. However, its establishment is technically complex and the experimental performance is limited by high failure rates, long experimental times and small sample sizes. We introduce an in-vitro multipatch setup with an automated pipette pressure and cleaning system facilitating recordings of up to 10 neurons simultaneously and sequential patching of additional neurons. We present hardware and software solutions that increase the usability, speed and data throughput of multipatch experiments which allowed probing of 150 synaptic connections between 17 neurons in one human cortical slice and screening of over 600 connections in tissue from a single patient. This method will facilitate the systematic analysis of microcircuits and allow unprecedented assessment of inter-individual variability.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 3, 4, 5 and 6.

Article and author information

Author details

Yangfan Peng

Institute of Neurophysiology, Charité-Universitätsmedizin Berlin, Berlin, Germany

For correspondence
yangfan.peng@charite.de

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-0317-1353
Franz Xaver Mittermaier

Institute of Neurophysiology, Charité-Universitätsmedizin Berlin, Berlin, Germany

Competing interests
The authors declare that no competing interests exist.
Henrike Planert

Institute of Neurophysiology, Charité-Universitätsmedizin Berlin, Berlin, Germany

Competing interests
The authors declare that no competing interests exist.
Ulf Christoph Schneider

Department of Neurosurgery, Charité-Universitätsmedizin Berlin, Berlin, Germany

Competing interests
The authors declare that no competing interests exist.
Henrik Alle

Institute of Neurophysiology, Charité-Universitätsmedizin Berlin, Berlin, Germany

Competing interests
The authors declare that no competing interests exist.
Jörg RP Geiger

Institute of Neurophysiology, Charité-Universitätsmedizin Berlin, Berlin, Germany

For correspondence
joerg.geiger@charite.de

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-9552-4322

Funding

Deutsche Forschungsgemeinschaft (EXC 257)

Jörg RP Geiger

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

Ethics

Animal experimentation: Animal handling and all procedures were carried out in accordance with guidelines of local authorities (Berlin, [T0215/11], [T0109/10]), the German Animal Welfare Act and the European Council Directive 86/609/EEC.

Human subjects: All patients gave a written consent for the scientific use of the resected tissue. All procedures adhered to ethical requirements and were in accordance to theapproval of the ethics committee of the Charité-Universitätsmedizin Berlin (EA2/111/14).

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.