2012
DOI: 10.1038/nmeth.1993
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Automated whole-cell patch-clamp electrophysiology of neurons in vivo

Abstract: Whole-cell patch clamp electrophysiology of neurons is a gold standard technique for high-fidelity analysis of the biophysical mechanisms of neural computation and pathology but it requires great skill to perform. We have developed a robot that automatically performs patch clamping in vivo, algorithmically detecting cells by analyzing the temporal sequence of electrode impedance changes. We demonstrate good yield, throughput, and quality of automated intracellular recording in mouse cortex and hippocampus.

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Cited by 220 publications
(240 citation statements)
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“…For instance, patch clamping of muscle, nerve or brain cells is a prime candidate for tight integration of wet-lab experiment and computer modelling. The robotized, high-throughput systems available (Kodandaramaiah et al, 2012;Kolb et al, 2013;Wood et al, 2004) already have their own formats for specifying voltage-stepping protocols, and excitable cells are among the best-modelled biological systems in public repositories (Box 2). It is a small step to use the same protocol specifications for wet-lab and virtual experiments, and thus streamline the confrontation of simulated and experimental data.…”
Section: Box 3: Expanding the Scope Of Virtual Experimentsmentioning
confidence: 99%
“…For instance, patch clamping of muscle, nerve or brain cells is a prime candidate for tight integration of wet-lab experiment and computer modelling. The robotized, high-throughput systems available (Kodandaramaiah et al, 2012;Kolb et al, 2013;Wood et al, 2004) already have their own formats for specifying voltage-stepping protocols, and excitable cells are among the best-modelled biological systems in public repositories (Box 2). It is a small step to use the same protocol specifications for wet-lab and virtual experiments, and thus streamline the confrontation of simulated and experimental data.…”
Section: Box 3: Expanding the Scope Of Virtual Experimentsmentioning
confidence: 99%
“…This complicated operation normally requires several months or even 1 year of training before the technician is able to reliably record from the cells [9] because of the difficulty in obtaining successful recording. This also significantly increases the cost of the whole patch clamp recording process.…”
Section: Introductionmentioning
confidence: 99%
“…52 On the three fronts of modeling, computation, and experiment, there have been a series of important recent advances, and many new avenues of research have emerged. These include: (1) new techniques to record high-density brain activity; [55][56][57] (2) theoretical advances and clinical application of deep brain stimulation methods; 58 (3) sophisticated biophysical models of rhythms and disease; 59,60 (4) novel optogenetic techniques that permit interrogation of neural circuits in vivo; 61 and, (5) increasingly-sophisticated data-analysis techniques. 62 The modeling and computational work-both deterministic and stochastic-have focused in part on reproducing experimental results, and on the investigation of the underlying biophysical and dynamical mechanisms, especially when experiments are not possible or very difficult to perform.…”
Section: Introductionmentioning
confidence: 99%