Kamudzandu, M, Köse-Dunn, M, Evans, MG, Fricker, RA and Roach, P (2019) A micro-fabricated in vitro complex neuronal circuit platform. Biomedical Physics & Engineering Express, 5 (4). 045016 - 045016. ISSN 2057-1976

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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 micro-channels, 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+ and K+ 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.

Item Type: Article
Additional Information: This is the final published version of the article (version of record). It first appeared online via IOP Publishing at https://doi.org/10.1088/2057-1976/ab2307 - please refer to any applicable terms of use of the publisher.
Uncontrolled Keywords: in vitro model, neuronal network, basal ganglia, microfluidic, 3Rs, brain-on-a-chip
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Medicine and Health Sciences > Institute for Science and Technology in Medicine
Depositing User: Symplectic
Date Deposited: 11 Jun 2019 15:54
Last Modified: 01 Jul 2019 08:19
URI: https://eprints.keele.ac.uk/id/eprint/6469

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