Kamudzandu_2019_Biomed._Phys._Eng._Express_5_045016.pdf (861.34 kB)
Download fileA micro-fabricated in vitro complex neuronal circuit platform
journal contribution
posted on 2019-06-12, 13:40 authored by M. Kamudzandu, Matthew Kose-Dunn, M.G. Evans, Rosemary Fricker, Paul RoachPaul RoachDevelopments 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 ExpressVolume
5Issue
4Pages
045016 - 045016Citation
KAMUDZANDU. M. ... et al., A micro-fabricated in vitro complex neuronal circuit platform. Biomedical Physics & Engineering Express, 5(4): 045016.Publisher
IOP PublishingVersion
- 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
2019-05-20Publication date
2019-06-03Copyright date
2019Notes
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
2057-1976Publisher version
Language
- en