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Striebel, J.

Publications and source records attributed to Striebel, J..

5 recordsLinked to original sources

Empirical validation of ephaptic coupling in printed human neural circuits

Ephaptic coupling is a phenomenon describing the influence of endogenous electric fields on neuronal activity1,2. Although ephaptic coupling is deemed to contribute to computations in the brain1,3,4, the olfactory system5, the retina6,7, and to cardiac conduction8,9, and being associated with diseases like epilepsy10,11 and arrhythmia12,13, it is still poorly understood since it is notoriously difficult to investigate in vivo and in vitro. In vitro electrophysiology allows accessible and flexible experimentation, but circuits form randomly, leading to a lack of precision and reproducibility. Here, we present a method for reproducibly constructing human neuronal networks in vitro with single-cell precision. We constructed neuronal circuits from the bottom up by bringing their axons into close contact. This enabled us to measure the effects of ephaptic coupling and validate theoretical predictions, such as reduced action potential velocity, increased activity synchronization14-16 and reduced stimulation threshold17. Our precise measurements of electrophysiological activity support the importance of ephaptic coupling in neuronal circuit function. Printed neuronal circuits allow detailed in vitro studies of neuronal interactions and may serve as a platform for disease modeling related to synaptic, ephaptic, or myelination processes.

bioengineering↗

A computational model of altered neuronal activity in altered gravity

Electrophysiological experiments have shown that neuronal activity changes upon exposure to altered gravity. More specifically, neurons firing rates increase during microgravity and decrease during centrifugal-induced hypergravity. Different biophysical explanations have been proposed for this phenomenon: however, they have not been backed by quantitative analyses nor simulations. More generally, classical computational models of neurons and networks do not account for the effect of altered gravity, which limits the possibility to perform in-silico experiments and simulations. Here, we propose computational implementations for different effects of altered gravity on cellular functions, and modify existing models to account for the effect of micro- and hyper-gravity. Firstly, in line with previous experiments, we suggest that microgravity could be modeled as an increase of the voltage-dependent channel transition rates, which is assumed to be the result of a higher membrane fluidity and can be readily implemented into the Hodgkin-Huxley model. Using in-silico simulations of single neurons, we show that this model of the influence of gravity on neuronal activity allows to reproduce the observed increased firing and burst rates. Secondly, we explore the role of mechano-gated (MG) ion channels on population activity. We show that recordings can be fitted by a network of connected excitatory neurons, whose activity is balanced by firing rate adaptation. Adding a small depolarizing current to account for the activation of MG channels also reproduces the observed increased firing and burst rates. Overall, our results fill an important gap in the literature, by providing a computational link between altered gravity and neuronal activity. Starting from historical observations of the effects of gravity on cellular functions, we derived gravity-sensitive models of neurons and networks, whose predictions could be refined using future experiments.

neuroscience↗

Microengineered 2D and 3D modular neuronal networks represent structure-function relationship

Brain function is substantially linked to the highly organized structure of neuronal networks. Emerging three-dimensional (3D) neuronal cell culture technologies attempt to mimic the complexity of brain circuits as in vitro microphysiological systems. Nevertheless, structures of in vitro assembled neuronal circuits often varies between samples and changes over time that makes it challenging to reliably record network functional output and link it to the network structure. Hence, engineering neuronal structures with pre- defined geometry and reproducible functional features are essential to model in vivo neuronal circuits in a robust way. Here, we engineered thin microchannel devices to assemble 2D and 3D modular networks. Microchannel devices were coupled with multi-electrode array (MEA) electrophysiology system to enable long-term electrophysiology recordings from microengineered circuits. Each network was composed of 64 micromodules which were connected through micron size channels to their adjacent modules. Microstructures physically confined neurons to the recording electrodes that considerably enhanced the electrophysiology readout efficiency. In addition, microstructures preserved modular network structure over weeks. Modular circuits within microfluidic devices showed consistent spatial patterns of activity over weeks, which was missing in the randomly formed circuits. Number of physical connections per module was shown to be influencing the measured activity and functional connectivity parameters, that represents the impact of network structure on its functional output. We show that microengineered 3D modular networks with a profound activity and higher number of functional connections recapitulate key functional features of developing cortex. Structurally and functionally stable 2D and 3D network mimic the modular architecture of brain circuits and offers a robust and reproducible in vitro microphysiolopgical system to serve basic and translational neuroscience research.

bioengineering↗

OME-Zarr: a cloud-optimized bioimaging file format with international community support

A growing community is constructing a next-generation file format (NGFF) for bioimaging to overcome problems of scalability and heterogeneity. Organized by the Open Microscopy Environment (OME), individuals and institutes across diverse modalities facing these problems have designed a format specification process (OME-NGFF) to address these needs. This paper brings together a wide range of those community members to describe the cloud-optimized format itself - OME-Zarr - along with tools and data resources available today to increase FAIR access and remove barriers in the scientific process. The current momentum offers an opportunity to unify a key component of the bioimaging domain -- the file format that underlies so many personal, institutional, and global data management and analysis tasks.

bioinformatics↗

Tracking long-term functional connectivity maps in human stem-cell-derived neuronal networks by holographic-optogenetic stimulation

Neuronal networks derived from human induced pluripotent stem cells (hiPSCs) have been exploited widely for modelling neuronal circuits, neurological diseases and drug screening. As these networks require extended culturing periods to functionally mature in vitro, most studies are based on immature networks. To obtain insights on long-term functional features of human networks, we improved a long-term glia-co-culture culturing protocol directly on multi-electrode arrays (MEA), facilitating long-term assessment of electrical features at weekly intervals. We applied optogenetic stimulation to induce neuronal activity, which resulted in accelerated neuronal responses during network development. Using holographic stimulation with single-cell-resolution, propagating evoked activities of 400 individually stimulated neurons per MEA were traceable, and precise network functional connectivity motifs were revealed. Our integrated holographic optogenetic stimulation platform on MEAs facilitates studying long-term functional dynamics of human neuronal networks in vitro. This is an important step towards establishing hiPSC-derived neurons as profound functional testbeds for basic and biomedical research. HighlightsO_LIIntegrated platform allowed long-term optogenetic experiments on hiPSC-derived networks. C_LIO_LIFull-field optogenetic stimulation boosted hiPSC-derived neuronal network activity. C_LIO_LISingle-neuron resolution holographic stimulation evoked local responses in the network. C_LIO_LIHolographic stimulation of each neuron revealed its functional connectivity patterns. C_LIO_LISubsequent holographic stimulation of more than 400 neurons revealed the whole network connectivity map. C_LI

neuroscience↗