Kamudzandu_2019_Biomed._Phys._Eng._Express_5_045016.pdf (861.34 kB)
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A micro-fabricated in vitro complex neuronal circuit platform

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posted on 12.06.2019, 13:40 authored by M. Kamudzandu, Matthew Kose-Dunn, M.G. Evans, Rosemary Fricker, Paul RoachPaul Roach
Developments in micro-manufacture as well as biofabrication technologies are driving our ability to create complex tissue models such as ‘organ-on-a-chip’ devices. The complexity of neural tissue, however, requires precisely specific cellular connectivity across many neuronal populations, and thus there have been limited reports of complex ‘brain-on-a-chip’ technologies modelling specific cellular circuit function. Here we describe the development of a model of in vitro brain circuitry designed to accurately reproduce part of the complex circuitry involved in neurodegenerative diseases; using segregated co-culture of specific basal ganglia (BG) neuronal subtypes to model central nervous system circuitry. Lithographic methods and chemical modification were used to form structured microchannels, which were populated by specifically cultured neuronal sub-types to represent parts of the inter-communicating neural circuit. Cell morphological assessment and immunostaining showed connectivity, which was supported by electrophysiology measurements. Electrical activity of cells was measured using patch-clamp, showing voltage dependant Na+ andK+ currents, and blocking of Na+ current by TTX, and calcium imaging showing TTX-sensitive slow Ca2+ oscillations resulting from action potentials. Monitoring cells across connected ports post-TTX addition demonstrated both upstream and downstream changes in activity, indicating network connectivity. The model developed herein provides a platform technology that could be used to better understand neurological function and dysfunction, contributing to a growing urgency for better treatments of neurodegenerative disease. We anticipate the use of this advancing technology for the assessment of pharmaceutical and cellular therapies as a means of pre-clinical assessment, and further for the advancement of neural engineering approaches for tissue engineering.

Funding

This work was supported by a Parkinson’sUK Innovation Grant K1302 to RF and PR. For part of the study, MKandMKDwere funded as doctoral students by the EPSRC Centre for Doctoral Training in Regenerative Medicine, held at Keele, Loughborough and Nottingham Universities (EP/F500491/1).

History

School

  • Science

Department

  • Chemistry

Published in

Biomedical Physics & Engineering Express

Volume

5

Issue

4

Pages

045016 - 045016

Citation

KAMUDZANDU. M. ... et al., A micro-fabricated in vitro complex neuronal circuit platform. Biomedical Physics & Engineering Express, 5(4): 045016.

Publisher

IOP Publishing

Version

VoR (Version of Record)

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution 3.0 Unported (CC BY 3.0) licence. Full details of this licence are available at: http://creativecommons.org/licenses/by/3.0/

Acceptance date

20/05/2019

Publication date

2019-06-03

Copyright date

2019

Notes

This is an Open Access Article. It is published by Elsevier under the Creative Commons Attribution 3.0 Unported Licence (CC BY). Full details of this licence are available at: http://creativecommons.org/licenses/by/3.0/

eISSN

2057-1976

Language

en