An experimental paradigm to investigate stimulation dependent activity in topologically constrained neuronal networks

Topologically controlled circuits of human iPSC-derived neurons for electrophysiology recordings

“…This is consistent with what was observed in circuits of rat primary networks. 69 Out of the 30 circuits from the two stimulated MEAs, 25 (83%) had a consistent electrical response upon stimulation of at least one of their electrodes, suggesting that functional connectivity takes place in most of the circuits. Overall, these stimulation results together with the synapses visualized by immunostaining are consistent with the presence of functional synapses.…”

“…4a ). The stimulation paradigm was based on Ihle et al 69 The 15 circuits of each MEA were electrically stimulated by sequentially applying a biphasic square pulse stimulus to each electrode of a circuit (top left, top right, bottom right, bottom left) at 2 Hz for 5 min ( Fig. 9a ).…”

“…Such bands are usually visible in the first 20 ms after the stimulus. 69 A full 500 ms response following a stimulus can be seen in Fig. S22.…”

Engineered Biological Neural Networks on High Density CMOS Microelectrode Arrays

“…Gaining high reproducibility in experiments using random in vitro neural networks has been a big challenge so far (Wagenaar et al, 2006 ; Keren, 2014 ; Napoli et al, 2014 ) and is the reason why the development of central nervous system (CNS)-related drugs has a longer development time and a lower success rate (Gribkoff and Kaczmarek, 2017 ). Using our directional PDMS microstructures mounted on CMOS arrays enables the design of multiple reproducible neural circuits with more predictable activity patterns that were shown to be highly stable under repeated stimulation (Ihle et al, 2022 ). One main reason why only 5 circuits showed the expected activity pattern is that we did not yet gain full control on the number of neurons per well.…”

“…Thus, PDMS microstructures allow full control over topology-relevant parameters such as the distance and directionality of connections between neurons. Previously, this method was used to implement engineered biological neural networks on 60-channel glass MEAs (Forró et al, 2018 ; Girardin et al, 2021 ; Ihle et al, 2022 ). The high compatibility of PDMS microstructures with the flat surface of standard glass MEAs allows the alignment of channels and microcompartments on top of each of the 60 electrodes (Forró et al, 2018 ).…”