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3D high-density microelectrode array with optical stimulation and drug delivery for investigating neural circuit dynamics.

ABSTRACT: Investigation of neural circuit dynamics is crucial for deciphering the functional connections among regions of the brain and understanding the mechanism of brain dysfunction. Despite the advancements of neural circuit models in vitro, technologies for both precisely monitoring and modulating neural activities within three-dimensional (3D) neural circuit models have yet to be developed. Specifically, no existing 3D microelectrode arrays (MEAs) have integrated capabilities to stimulate surrounding neurons and to monitor the temporal evolution of the formation of a neural network in real time. Herein, we present a 3D high-density multifunctional MEA with optical stimulation and drug delivery for investigating neural circuit dynamics within engineered 3D neural tissues. We demonstrate precise measurements of synaptic latencies in 3D neural networks. We expect our 3D multifunctional MEA to open up opportunities for studies of neural circuits through precise, in vitro investigations of neural circuit dynamics with 3D brain models.

SUBMITTER: Shin H

PROVIDER: S-EPMC7820464 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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3D high-density microelectrode array with optical stimulation and drug delivery for investigating neural circuit dynamics.

Shin Hyogeun H Jeong Sohyeon S Lee Ju-Hyun JH Sun Woong W Choi Nakwon N Cho Il-Joo IJ

Nature communications 20210121 1

Investigation of neural circuit dynamics is crucial for deciphering the functional connections among regions of the brain and understanding the mechanism of brain dysfunction. Despite the advancements of neural circuit models in vitro, technologies for both precisely monitoring and modulating neural activities within three-dimensional (3D) neural circuit models have yet to be developed. Specifically, no existing 3D microelectrode arrays (MEAs) have integrated capabilities to stimulate surroundin ...[more]

PMID: 33479237

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Project description:Emerging complementary metal oxide semiconductor (CMOS)-based, high-density microelectrode array (HD-MEA) devices provide high spatial resolution at subcellular level and a large number of readout channels. These devices allow for simultaneous recording of extracellular activity of a large number of neurons with every neuron being detected by multiple electrodes. To analyze the recorded signals, spiking events have to be assigned to individual neurons, a process referred to as "spike sorting." For a set of observed signals, which constitute a linear mixture of a set of source signals, independent component (IC) analysis (ICA) can be used to demix blindly the data and extract the individual source signals. This technique offers great potential to alleviate the problem of spike sorting in HD-MEA recordings, as it represents an unsupervised method to separate the neuronal sources. The separated sources or ICs then constitute estimates of single-neuron signals, and threshold detection on the ICs yields the sorted spike times. However, it is unknown to what extent extracellular neuronal recordings meet the requirements of ICA. In this paper, we evaluate the applicability of ICA to spike sorting of HD-MEA recordings. The analysis of extracellular neuronal signals, recorded at high spatiotemporal resolution, reveals that the recorded data cannot be modeled as a purely linear mixture. As a consequence, ICA fails to separate completely the neuronal signals and cannot be used as a stand-alone method for spike sorting in HD-MEA recordings. We assessed the demixing performance of ICA using simulated data sets and found that the performance strongly depends on neuronal density and spike amplitude. Furthermore, we show how postprocessing techniques can be used to overcome the most severe limitations of ICA. In combination with these postprocessing techniques, ICA represents a viable method to facilitate rapid spike sorting of multidimensional neuronal recordings.

Dataset Information

3D high-density microelectrode array with optical stimulation and drug delivery for investigating neural circuit dynamics.

Publications

3D high-density microelectrode array with optical stimulation and drug delivery for investigating neural circuit dynamics.

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