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

Girardin, Sophie; Clément, Blandine; Ihle, Stephan J.; Weaver, Sean; Petr, Jana B; Mateus, José C.; Duru, Jens; Krubner, Magdalena; Forró, Csaba; Ruff, Tobias; Fruh, Isabelle; Müller, Matthias; Vörös, János

doi:10.1039/d1lc01110c

Cited by 19 publications

(31 citation statements)

References 76 publications

(90 reference statements)

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“…Polydimethylsiloxane (PDMS) microstructures were based on a previously published design and prepared as described in Girardin et al (2022). PDMS microstructures consist of a micropatterned two-layer 120 mm thin membrane fabricated by Wunderlichips (Switzerland).…”

Section: Pdms Microstructuresmentioning

confidence: 99%

“…NBD supplemented with 10 mM of Rho-Kinase Inhibitor Y27632 (10 mM in PBS, 688000, Sigma Aldrich), as this was shown to improve survival of thawed iPSC-derived cells (Chen et al, 2021). From day in vitro (DIV) 0 to 7, NBD was also supplemented with 5 mg/mL of laminin (11243217001, Sigma Aldrich) to help with neuron survival (Girardin et al, 2022). From DIV 4 to 9, glia-containing samples were cultured with NBD supplemented with 2 mM of cytosine-b-D-arabinofuranoside (AraC, 500 mM in ultrapure water, C1768, Sigma Aldrich) to inhibit astrocyte and microglia proliferation.…”

Section: Cell Culture Medium Preparationmentioning

confidence: 99%

“…Electrophysiological experiments were performed using 60-electrode microelectrode arrays (60MEA500/30iR-Ti-gr, Multi Channel Systems). Substrates were prepared according to the protocol detailed in Girardin et al (2022), which includes a Poly-D-lysine (PDL, P6407, Sigma Aldrich) coating of substrates and alignment of the PDMS microstructures on the substrates (MEA or glass-bottom dish), as shown in Fig. 1B.…”

Section: Substrate Preparationmentioning

confidence: 99%

“…9A), termed the "stomach" shape, was optimized to guide axons to connect the nodes of a circuit in the clockwise direction (Forró et al, 2018). Based on the observation of hundreds of images of single iNeurons growing in such structures, axons were reported to grow in the clockwise direction between the two nodes of a stomach-shaped circuit in 90.6% of the cases (Girardin et al, 2022). As axons usually transmit action potentials from the axon initial segment to the post-synaptic terminals, controlling the direction of axon growth is expected to influence the main direction of action potential propagation in a network.…”

Section: Action Potentials Predominantly Travel In the Clockwise Dire...mentioning

confidence: 99%

“…Bottom-up neuroscience focuses on building and studying elementary circuits of neurons to infer the principles of more complex assemblies, with the main goal of getting a better understanding of the mechanisms behind information processing in the brain (Aebersold et al, 2016). Bottom-up neuroscience tools allow to build multiple, topologically-controlled circuits of tens to hundreds of neurons, which can be electrically stimulated and recorded from in parallel using microelectrode arrays (MEA) (Forro et al, 2018; Ihle et al, 2022; Duru et al, 2022; Girardin et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

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Engineering circuits of human iPSC-derived neurons and rat primary glia

Girardin

Ihle

Menghini

et al. 2022

Preprint

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Novel in vitro platforms based on human neurons are needed to improve early drug testing and address the stalling drug discovery in neurological disorders. Topologically controlled circuits of human induced pluripotent stem cell (iPSC)-derived neurons have the potential to become such a testing system. In this work, we build in vitro co-cultured circuits of human iPSC-derived neurons and rat primary glial cells using microfabricated polydimethylsiloxane (PDMS) structures on microelectrode arrays (MEAs). Such circuits are created by seeding either dissociated cells or pre-aggregated spheroids at different neuron-to-glia ratios. Furthermore, an antifouling coating is developed to prevent axonal overgrowth in undesired locations of the microstructure. We assess the electrophysiological properties of different types of circuits over more than 50 days, including their stimulation-induced neural activity. Finally, we demonstrate the effect of magnesium chloride on the electrical activity of our iPSC circuits as a proof-of-concept for screening of neuroactive compounds.

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Section: Pdms Microstructuresmentioning

confidence: 99%

Section: Cell Culture Medium Preparationmentioning

confidence: 99%

Section: Substrate Preparationmentioning

confidence: 99%

Section: Action Potentials Predominantly Travel In the Clockwise Dire...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Engineering circuits of human iPSC-derived neurons and rat primary glia

Girardin

Ihle

Menghini

et al. 2022

Preprint

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Toward the Next Generation of Neural Iontronic Interfaces

Forró

Musall

Montes³

et al. 2023

Adv Healthcare Materials

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Neural interfaces are evolving at a rapid pace owing to advances in material science and fabrication, reduced cost of scalable complementary metal oxide semiconductor (CMOS) technologies, and highly interdisciplinary teams of researchers and engineers that span a large range from basic to applied and clinical sciences. This study outlines currently established technologies, defined as instruments and biological study systems that are routinely used in neuroscientific research. After identifying the shortcomings of current technologies, such as a lack of biocompatibility, topological optimization, low bandwidth, and lack of transparency, it maps out promising directions along which progress should be made to achieve the next generation of symbiotic and intelligent neural interfaces. Lastly, it proposes novel applications that can be achieved by these developments, ranging from the understanding and reproduction of synaptic learning to live‐long multimodal measurements to monitor and treat various neuronal disorders.

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