scholarly journals 3F(eature)s model: modularity, heterogeneity and three-dimensionality to design in vitro neuronal model

2021 ◽  
Vol 4 (s1) ◽  
Author(s):  
Martina Brofiga ◽  
Marietta Pisano ◽  
Mariateresa Tedesco ◽  
Francesca Callegari ◽  
Paolo Massobrio
Keyword(s):  
Three Dimensional ◽  
Neuronal Model ◽  
Neuronal Cultures ◽  
Electrode Arrays ◽  
Experimental Platform ◽  
Electrophysiological Activity ◽  
Micro Electrode Arrays ◽  
S Model

In this work, we present a novel experimental platform to build in vitro interconnected (i.e., modular) heterogeneous (e.g., cortical-hippocampal) and three-dimensional (3D) neuronal cultures plated on Micro-Electrode Arrays (MEAs) to extracellularly record the electrophysiological activity continuously.

Multiscale functional connectivity estimation on low-density neuronal cultures recorded by high-density CMOS Micro Electrode Arrays

2012 ◽  
Vol 207 (2) ◽  
pp. 161-171 ◽  
Author(s):  
Alessandro Maccione ◽  
Matteo Garofalo ◽  
Thierry Nieus ◽  
Mariateresa Tedesco ◽  
Luca Berdondini ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
High Density ◽  
Neuronal Cultures ◽  
Low Density ◽  
Electrode Arrays ◽  
Micro Electrode Arrays

scholarly journals Microdevice for directional axodendritic connectivity between micro 3D neuronal cultures

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yixuan Ming ◽  
Md Joynal Abedin ◽  
Svetlana Tatic-Lucic ◽  
Yevgeny Berdichevsky
Keyword(s):  
Three Dimensional ◽  
Basic Feature ◽  
Neuronal Cultures ◽  
The Novel ◽  
Cortical Circuits ◽  
Cortical Cells ◽  
Neuroscience Research ◽  
Directional Connectivity ◽  
Novel Concept

AbstractNeuronal cultures are widely used in neuroscience research. However, the randomness of circuits in conventional cultures prevents accurate in vitro modeling of cortical development and of the pathogenesis of neurological and psychiatric disorders. A basic feature of cortical circuits that is not captured in standard cultures of dissociated cortical cells is directional connectivity. In this work, a polydimethylsiloxane (PDMS)-based device that achieves directional connectivity between micro 3D cultures is demonstrated. The device consists of through-holes for micro three-dimensional (μ3D) clusters of cortical cells connected by microtrenches for axon and dendrite guidance. The design of the trenches relies in part on the concept of axonal edge guidance, as well as on the novel concept of specific dendrite targeting. This replicates dominant excitatory connectivity in the cortex, enables the guidance of the axon after it forms a synapse in passing (an “en passant” synapse), and ensures that directional selectivity is preserved over the lifetime of the culture. The directionality of connections was verified morphologically and functionally. Connections were dependent on glutamatergic synapses. The design of this device has the potential to serve as a building block for the reconstruction of more complex cortical circuits in vitro.

scholarly journals Opportunities and challenges for the use of induced pluripotent stem cells in modelling neurodegenerative disease

Open Biology ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 180177 ◽  
Author(s):  
Yi-Ying Wu ◽  
Feng-Lan Chiu ◽  
Chan-Shien Yeh ◽  
Hung-Chih Kuo
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Three Dimensional ◽  
Disease Patient ◽  
Neuronal Cultures ◽  
Sporadic Disease ◽  
Induced Pluripotent ◽  
Human Ipsc

Adult-onset neurodegenerative diseases are among the most difficult human health conditions to model for drug development. Most genetic or toxin-induced cell and animal models cannot faithfully recapitulate pathology in disease-relevant cells, making it excessively challenging to explore the potential mechanisms underlying sporadic disease. Patient-derived induced pluripotent stem cells (iPSCs) can be differentiated into disease-relevant neurons, providing an unparalleled platform for in vitro modelling and development of therapeutic strategies. Here, we review recent progress in generating Alzheimer's, Parkinson's and Huntington's disease models from patient-derived iPSCs. We also describe novel discoveries of pathological mechanisms and drug evaluations that have used these patient iPSC-derived neuronal models. Additionally, current human iPSC technology allows researchers to model diseases with 3D brain organoids, which are more representative of tissue architecture than traditional neuronal cultures. We discuss remaining challenges and emerging opportunities for the use of three-dimensional brain organoids in modelling brain development and neurodegeneration.

scholarly journals Cadherin-13 is a critical regulator of GABAergic modulation in human stem-cell-derived neuronal networks

2021 ◽  
Author(s):  
Britt Mossink ◽  
Jon-Ruben van Rhijn ◽  
Shan Wang ◽  
Katrin Linda ◽  
Maria R. Vitale ◽  
...  
Keyword(s):  
Gabaergic Neurons ◽  
Inhibitory Synapses ◽  
Disease Genes ◽  
Electrode Arrays ◽  
Glutamatergic Neurons ◽  
Human Neurons ◽  
Induced Pluripotent ◽  
Micro Electrode Arrays ◽  
Gabaergic Modulation

AbstractActivity in the healthy brain relies on a concerted interplay of excitation (E) and inhibition (I) via balanced synaptic communication between glutamatergic and GABAergic neurons. A growing number of studies imply that disruption of this E/I balance is a commonality in many brain disorders; however, obtaining mechanistic insight into these disruptions, with translational value for the patient, has typically been hampered by methodological limitations. Cadherin-13 (CDH13) has been associated with autism and attention-deficit/hyperactivity disorder. CDH13 localizes at inhibitory presynapses, specifically of parvalbumin (PV) and somatostatin (SST) expressing GABAergic neurons. However, the mechanism by which CDH13 regulates the function of inhibitory synapses in human neurons remains unknown. Starting from human-induced pluripotent stem cells, we established a robust method to generate a homogenous population of SST and MEF2C (PV-precursor marker protein) expressing GABAergic neurons (iGABA) in vitro, and co-cultured these with glutamatergic neurons at defined E/I ratios on micro-electrode arrays. We identified functional network parameters that are most reliably affected by GABAergic modulation as such, and through alterations of E/I balance by reduced expression of CDH13 in iGABAs. We found that CDH13 deficiency in iGABAs decreased E/I balance by means of increased inhibition. Moreover, CDH13 interacts with Integrin-β1 and Integrin-β3, which play opposite roles in the regulation of inhibitory synaptic strength via this interaction. Taken together, this model allows for standardized investigation of the E/I balance in a human neuronal background and can be deployed to dissect the cell-type-specific contribution of disease genes to the E/I balance.

scholarly journals Engineered biological neural networks on high density CMOS micro electrode arrays

2021 ◽  
Author(s):  
Jens Duru ◽  
Joel Kuechler ◽  
Stephan Johannes Ihle ◽  
Csaba Forro ◽  
Aeneas Bernardi ◽  
...  
Keyword(s):  
Neural Networks ◽  
Network Topology ◽  
Complementary Metal Oxide Semiconductor ◽  
High Density ◽  
Oxide Semiconductor ◽  
Electrode Arrays ◽  
Spatiotemporal Resolution ◽  
Biological Neural Networks ◽  
Micro Electrode Arrays

In bottom-up neuroscience, questions on neural information processing are addressed by engineering small but reproducible biological neural networks of defined network topology \textit{in vitro}. The network topology can be controlled by culturing neurons within polydimethylsiloxane (PDMS) microstructures that are combined with microelectrode arrays (MEAs) for electric access to the network. However, currently used glass MEAs are limited to 256 electrodes and pose a limitation to the spatial resolution as well as the design of more complex microstructures. The use of high density complementary metal-oxide-semiconductor (CMOS) MEAs greatly increases the spatiotemporal resolution, enabling sub-cellular readout and stimulation of neurons in defined neural networks. Unfortunately, the non-planar surface of CMOS MEAs complicates the attachment of PDMS microstructures. To overcome the problem of axons escaping the microstructures through the ridges of the CMOS MEA, we stamp-transferred a thin film of hexane-diluted PDMS onto the array such that the PDMS filled the ridges at the contact surface of the microstructures without clogging the axon guidance channels. Moreover, we provide an impedance-based method to visualize the exact location of the microstructures on the MEA and show that our method can confine axonal growth within the PDMS microstructures. Finally, the high spatiotemporal resolution of the CMOS MEA enabled us to show that we can guide action potentials using the unidirectional topology of our circular multi-node microstructure.

scholarly journals Human neuronal networks on micro-electrode arrays are a highly robust tool to study disease-specific genotype-phenotype correlations in vitro

2021 ◽  
Author(s):  
B. Mossink ◽  
A.H.A. Verboven ◽  
E.J.H. van Hugte ◽  
T.M. Klein Gunnewiek ◽  
G. Parodi ◽  
...  
Keyword(s):  
Experimental Design ◽  
Neuronal Network ◽  
Neuronal Networks ◽  
Network Activity ◽  
Full Potential ◽  
Electrode Arrays ◽  
Neuronal Network Activity ◽  
Micro Electrode Arrays ◽  
Disease Specific

AbstractMicro-electrode arrays (MEAs) are increasingly used to characterize neuronal network activity of human induced pluripotent stem-cell (hiPSC)-derived neurons. Despite their gain in popularity, MEA recordings from hiPSC-derived neuronal networks are not always used to their full potential in respect to experimental design, execution and data analysis. Therefore, we benchmarked the robustness and sensitivity of MEA-derived neuronal activity patterns derived from ten healthy individual control lines. We provide recommendations on experimental design and analysis to achieve standardization. With such standardization, MEAs can be used as a reliable platform to distinguish (disease-specific) network phenotypes. In conclusion, we show that MEAs are a powerful and robust tool to uncover functional neuronal network phenotypes from hiPSC-derived neuronal networks, and provide an important resource to advance the hiPSC field towards the use of MEAs for disease-phenotyping and drug discovery.

Sign in / Sign up

Export Citation Format

Share Document