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

View ORCID ProfileYangfan Peng, Franz X. Mittermaier, Henrike Planert, Ulf C. Schneider, Henrik Alle, View ORCID ProfileJörg R.P. Geiger
doi: https://doi.org/10.1101/639328
Yangfan Peng
1Institute of Neurophysiology, Charité – Universitätsmedizin Berlin, Germany
2Department of Neurology, Charité – Universitätsmedizin Berlin, Germany
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Franz X. Mittermaier
1Institute of Neurophysiology, Charité – Universitätsmedizin Berlin, Germany
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Henrike Planert
1Institute of Neurophysiology, Charité – Universitätsmedizin Berlin, Germany
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Ulf C. Schneider
3Department of Neurosurgery, Charité – Universitätsmedizin Berlin, Germany
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Henrik Alle
1Institute of Neurophysiology, Charité – Universitätsmedizin Berlin, Germany
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Jörg R.P. Geiger
1Institute of Neurophysiology, Charité – Universitätsmedizin Berlin, Germany
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  • For correspondence: [email protected]
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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 comparisons at the level of individuals.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted May 18, 2019.
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High-throughput microcircuit analysis of individual human brains through next-generation multineuron patch-clamp
Yangfan Peng, Franz X. Mittermaier, Henrike Planert, Ulf C. Schneider, Henrik Alle, Jörg R.P. Geiger
bioRxiv 639328; doi: https://doi.org/10.1101/639328
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High-throughput microcircuit analysis of individual human brains through next-generation multineuron patch-clamp
Yangfan Peng, Franz X. Mittermaier, Henrike Planert, Ulf C. Schneider, Henrik Alle, Jörg R.P. Geiger
bioRxiv 639328; doi: https://doi.org/10.1101/639328

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