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

Peng Y
Mittermaier FX
Planert H
Schneider UC
Alle H
Geiger JRP
Scientific 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.

Citation
2019. Elife, 8
DOI
10.7554/eLife.48178
Publication
Denison T, Rogers DJ, Memarian Sorkhabi M
2021. WO/2021/176219
Publication
Pavlides A, Hogan SJ, Bogacz R

2015.PLoS Comput. Biol., 11(12):e1004609.

Publication
Fischer P, Tan H, Pogosyan A, Brown P

2016.Eur. J. Neurosci., 44(5):2202-13.

Publication
Arruda BS, Reis C, Sermon JJ, Pogosyan A, Brown P, Cagnan H
2021. J. Neuroeng. Rehabil., 18(1):179.
Publication
Malhotra G, Leslie DS, Ludwig CJ, Bogacz R
2018.Psychon Bull Rev, 25(3):971-996.