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Issue 17, 2020
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Extracellular recording of direct synaptic signals with a CMOS-nanoelectrode array

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Abstract

The synaptic connections between neurons are traditionally determined by correlating the action potentials (APs) of a pre-synaptic neuron and small-amplitude subthreshold potentials of a post-synaptic neuron using invasive intracellular techniques, such as patch clamping. Extracellular recording by a microelectrode array can non-invasively monitor network activities of a large number of neurons, but its reduced sensitivity usually prevents direct measurements of synaptic signals. Here, we demonstrate that a newly developed complementary metal-oxide-semiconductor (CMOS) nanoelectrode array (CNEA) is capable of extracellularly determining direct synaptic connections in dense, multi-layer cultures of dissociated rat neurons. We spatiotemporally correlate action potential signals of hundreds of active neurons, detect small (∼1 pA after averaging) extracellular synaptic signals at the region where pre-synaptic axons and post-synaptic dendrites/somas overlap, and use those signals to map synaptic connections. We use controlled stimulation to assess stimulation-dependent synaptic strengths and to titrate a synaptic blocker (CNQX: IC50 ∼ 1 μM). The new capabilities demonstrated here significantly enhance the utilities of CNEAs in connectome mapping and drug screening applications.

Graphical abstract: Extracellular recording of direct synaptic signals with a CMOS-nanoelectrode array

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Supplementary files

Article information


Submitted
27 May 2020
Accepted
29 Jul 2020
First published
30 Jul 2020

Lab Chip, 2020,20, 3239-3248
Article type
Paper

Extracellular recording of direct synaptic signals with a CMOS-nanoelectrode array

J. Abbott, T. Ye, K. Krenek, R. S. Gertner, W. Wu, H. S. Jung, D. Ham and H. Park, Lab Chip, 2020, 20, 3239
DOI: 10.1039/D0LC00553C

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