Investigation of the Input-Output Relationship of Engineered Neural Networks Using High-Density Microelectrode Arrays

15 Pages Posted: 24 Apr 2023

See all articles by Jens Duru

Jens Duru

affiliation not provided to SSRN

Benedikt Maurer

affiliation not provided to SSRN

Ciara Giles Doran

affiliation not provided to SSRN

Robert Jelitto

affiliation not provided to SSRN

Joel Küchler

affiliation not provided to SSRN

Stephan J. Ihle

affiliation not provided to SSRN

Tobias Ruff

affiliation not provided to SSRN

Robert John

affiliation not provided to SSRN

Barbara Genocchi

Tampere University

Janos Voros

affiliation not provided to SSRN

Abstract

Bottom-up neuroscience utilizes small, engineered biological neural networks to study neuronal activity in systems of reduced complexity. We present a platform that establishes up to six independent networks formed by primary rat neurons on planar complementary metal–oxide–semiconductor (CMOS) microelectrode arrays (MEAs). We introduce an approach that allows repetitive stimulation and recording of network activity at any of the over 700 electrodes underlying a network. We demonstrate that the continuous application of a repetitive super-threshold stimulus yields a reproducible network answer within a 15 ms post-stimulus window. This response can be tracked with high spatiotemporal resolution across the whole extent of the network. Moreover, we show that the location of the stimulation plays a significant role in the networks’ early response to the stimulus. By applying a stimulation pattern to all network-underlying electrodes in sequence, the sensitivity of the whole network to the stimulus can be visualized. We demonstrate that microchannels reduce the voltage stimulation threshold and induce the strongest network response. By varying the stimulation amplitude and frequency we reveal discrete network transition points. Finally, we introduce vector fields to follow stimulation-induced spike propagation pathways within the network. Overall we show that our defined neural networks on CMOS MEAs enable us to elicit highly reproducible activity patterns that can be precisely modulated by stimulation amplitude, stimulation frequency and the site of stimulation.

Keywords: Bottom-up neuroscienceMicrophysiological systemsControlled neural networksPDMS microstructuresElectrical stimulationActivity modulation

Suggested Citation

Duru, Jens and Maurer, Benedikt and Giles Doran, Ciara and Jelitto, Robert and Küchler, Joel and Ihle, Stephan J. and Ruff, Tobias and John, Robert and Genocchi, Barbara and Voros, Janos, Investigation of the Input-Output Relationship of Engineered Neural Networks Using High-Density Microelectrode Arrays. Available at SSRN: https://ssrn.com/abstract=4427959 or http://dx.doi.org/10.2139/ssrn.4427959

Jens Duru

affiliation not provided to SSRN ( email )

No Address Available

Benedikt Maurer

affiliation not provided to SSRN ( email )

No Address Available

Ciara Giles Doran

affiliation not provided to SSRN ( email )

No Address Available

Robert Jelitto

affiliation not provided to SSRN ( email )

No Address Available

Joel Küchler

affiliation not provided to SSRN ( email )

No Address Available

Stephan J. Ihle

affiliation not provided to SSRN ( email )

No Address Available

Tobias Ruff

affiliation not provided to SSRN ( email )

No Address Available

Robert John

affiliation not provided to SSRN ( email )

No Address Available

Barbara Genocchi

Tampere University ( email )

Tampere, FIN-33101
Finland

Janos Voros (Contact Author)

affiliation not provided to SSRN ( email )

No Address Available

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