Chronic Electrical Stimulation Promotes the Excitability and Plasticity of ESC-derived Neurons following Glutamate-induced Inhibition In vitro

Latchoumane, Charles; Jackson, Ladonya; Sendi, Mohammad S.E.; Tehrani, Kayvan Forouhesh; Mortensen, Luke J.; Stice, Steven L.; Ghovanloo, Maysam; Karumbaiah, Lohitash

doi:10.1038/s41598-018-29069-3

Cited by 36 publications

(25 citation statements)

References 97 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Whereas it is true that in some cases neurostimulation may promote inhibitory activity, sometimes this leads to excitation in other connected brain regions. Perhaps more accurate would be to say that neurostimulation alters the patterns of synchronous activity (Latchoumane et al, 2018; Hu et al, 2019). Illustrations of the favorable effects on neuropathologies of non-specific neurostimulation are numerous; to wit, there is evidence that DBS promotes memory (Ezzyat et al, 2017) and non-invasive neurostimulation (rTMS and tDCS) enhances performances on several cognitive functions impaired in Alzheimer disease while some promising results with invasive DBS have also been observed (Nardone et al, 2015).…”

Section: Improving Healthy Brain Dynamicsmentioning

confidence: 99%

On a Simple General Principle of Brain Organization

2019

View full text Add to dashboard Cite

A possible framework to characterize nervous system dynamics and its organization in conscious and unconscious states is introduced, derived from a high level perspective on the coordinated activity of brain cell ensembles. Some questions are best addressable in a global framework and here we build on past observations about the structure of configurations of brain networks in conscious and unconscious states and about neurophysiological results. Aiming to bind some results together into some sort of coherence with a central theme, the scenario that emerges underscores the crucial importance of the creation and dissipation of energy gradients in brain cellular ensembles resulting in maximization of the configurations in the functional connectivity among those networks that favor conscious awareness and healthy conditions. These considerations are then applied to indicate approaches that can be used to improve neuropathological syndromes.

show abstract

Section: Improving Healthy Brain Dynamicsmentioning

confidence: 99%

On a Simple General Principle of Brain Organization

2019

View full text Add to dashboard Cite

show abstract

“…Mouse embryonic stem cells were cultured and differentiated, resulting in cultures containing a mixture of motor neurons, excitatory and inhibitory neurons, and glial cells [11]. These neural cultures were allowed to mature on 48-well MEA plates over a 19-day period, typical for neuron maturation and network formation for these cells [12]. Activity was detected at approximately 5 days post-seeding (days in vitro; DIV) and increased gradually until reaching a plateau over the last several days of recording (16-19 DIV).…”

Section: Resultsmentioning

confidence: 99%

Development of an objective index, neural activity score (NAS), reveals neural network ontogeny and treatment effects on microelectrode arrays

Passaro

Aydin

Saif

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Microelectrode arrays (MEAs) are valuable tools for electrophysiological analysis at a cellular population level, providing assessment of neural network health and development. Analysis can be complex, however, requiring intensive processing of large high-dimensional data sets consisting of many activity parameters. As a result, valuable information is lost, as studies subjectively report relatively few metrics in the interest of simplicity and clarity.From a screening perspective, many groups report simple overall activity; we are more interested in culture health and changes in network connectivity that may not be evident from basic activity parameters. For example, general changes in overall firing rate – the most commonly reported parameter – provide no information on network development or burst character, which could change independently. Our goal was to develop a fast objective process to capture most, if not all, the valuable information gained when using MEAs in neural development and toxicity studies.We implemented principal component analysis (PCA) to reduce the high dimensionality of MEA data. Upon analysis, we found that the first principal component was strongly correlated to time, representing neural culture development; therefore, factor loadings were used to create a single index score – named neural activity score (NAS) – reflective of neural maturation. To validate this score, we applied it to studies analyzing various treatments. In all cases, NAS accurately recapitulated expected results, suggesting this method is viable. This approach may be improved with larger training data sets and can be shared with other researchers using MEAs to analyze complicated treatment effects and multicellular interactions.Author SummaryAnalyzing neural activity has important applications such as basic neuroscience research, understanding neurological diseases, drug development, and toxicity screening. Technology for recording neural activity continues to develop, producing large data sets that provide complex information about neuronal function. One specific technology, microelectrode arrays (MEAs), has recently given researchers the ability to record developing neural networks with potential to provide valuable insight into developmental processes and pathological conditions. However, the complex data generated by these systems can be challenging to analyze objectively and quantitatively, hindering the potential of MEAs, especially for high-throughput approaches, such as drug development and toxicity screening, which require quick, simple, and accurate quantification. Therefore, we have developed an index for simple quantification and evaluation of neural network maturation and the effects of perturbation. We present validation of our approach using several treatments and culture conditions, as well as a meta-analysis of toxicological screening data to compare our approach to current methods. In addition to providing a simple quantification method for neural network activity in various conditions, our method provides potential for improved results interpretation in toxicity screening and drug development.

show abstract

“…Traditional electrophysiological data processing is typically carried out in a similar fashion, regardless of recording method. For action potential (spike) and burst analysis, recorded signals are high pass filtered, followed by spike detection and sorting, and finally parameter calculation from the analyzed spike patterns ( Robinette et al, 2011 ; Latchoumane et al, 2018 ). Many labs perform these steps with custom scripts, but there is also a litany of commercial and open source software solutions available ( Egert et al, 2002 ; Pastore et al, 2016 ; Bridges et al, 2018 ; Unakafova and Gail, 2019 ), which may be useful when adapting these analyses to 3D recordings, especially for researchers without a strong background in electrophysiology that may be analyzing brain organoids.…”

Section: Recent Advances In Electrophysiology—applicability To Brainmentioning

confidence: 99%

Electrophysiological Analysis of Brain Organoids: Current Approaches and Advancements

Passaro

Stice

2021

Front. Neurosci.

Self Cite

View full text Add to dashboard Cite

Brain organoids, or cerebral organoids, have become widely used to study the human brain in vitro. As pluripotent stem cell-derived structures capable of self-organization and recapitulation of physiological cell types and architecture, brain organoids bridge the gap between relatively simple two-dimensional human cell cultures and non-human animal models. This allows for high complexity and physiological relevance in a controlled in vitro setting, opening the door for a variety of applications including development and disease modeling and high-throughput screening. While technologies such as single cell sequencing have led to significant advances in brain organoid characterization and understanding, improved functional analysis (especially electrophysiology) is needed to realize the full potential of brain organoids. In this review, we highlight key technologies for brain organoid development and characterization, then discuss current electrophysiological methods for brain organoid analysis. While electrophysiological approaches have improved rapidly for two-dimensional cultures, only in the past several years have advances been made to overcome limitations posed by the three-dimensionality of brain organoids. Here, we review major advances in electrophysiological technologies and analytical methods with a focus on advances with applicability for brain organoid analysis.

show abstract

Chronic Electrical Stimulation Promotes the Excitability and Plasticity of ESC-derived Neurons following Glutamate-induced Inhibition In vitro

Cited by 36 publications

References 97 publications

On a Simple General Principle of Brain Organization

On a Simple General Principle of Brain Organization

Development of an objective index, neural activity score (NAS), reveals neural network ontogeny and treatment effects on microelectrode arrays

Electrophysiological Analysis of Brain Organoids: Current Approaches and Advancements

Contact Info

Product

Resources

About