AUTHOR=Amos Giulia , Ihle Stephan J. , Clément Blandine F. , Duru Jens , Girardin Sophie , Maurer Benedikt , Delipinar Tuğçe , Vörös János , Ruff Tobias 

TITLE=Engineering an in vitro retinothalamic nerve model

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 18 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2024.1396966

DOI=10.3389/fnins.2024.1396966

ISSN=1662-453X

ABSTRACT=Understanding the retinogeniculate pathway in vitro can offer insights into its development and potential for future therapeutic applications. This study presents a Polydimethylsiloxanebased two-chamber system with axon guidance channels, designed to replicate unidirectional retinogeniculate signal transmission in vitro.In the presented model we integrated up to 20 identical functional retinothalamic neural networks on a single transparent microelectrode array, enhancing the robustness and quality of recorded functional data. Using embryonic rat retinas, we developed a model where retinal spheroids innervate thalamic targets through up to 6 mm long microfluidic channels. We found that network integrity depends on channel length, with 0.5-2 mm channels maintaining over 90 % morphological and 40 % functional integrity. A reduced network integrity was recorded in longer channels. The results indicate a notable reduction in forward spike propagation in channels longer than 4 mm. Additionally, spike conduction fidelity decreased with increasing channel length. Yet, stimulation-induced thalamic target activity remained unaffected by channel length. Finally, we assessed the impact of stimulation frequency and channel length on the sustainability of the thalamic target spheroid response. The study found that a sustained thalamic calcium response could be elicited with stimulation frequencies up to 31 Hz, with higher frequencies leading to transient responses. In conclusion, this study presents a high-throughput platform that demonstrates how channel length affects retina to brain network formation and signal transmission in vitro.