Improvement of impaired electrical activity in NPC1 mutant cortical neurons upon DHPG stimulation detected by micro-electrode array

Feng, Xiao; Bader, Benjamin; Yang, Fan; Segura, Mònica; Schultz, Luise; Schröder, Olaf; Rolfs, Arndt; Luo, Jiankai

doi:10.1016/j.brainres.2018.05.009

Cited by 8 publications

(6 citation statements)

References 57 publications

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“…Assessing several methodological aspects of MEA experiments, many of the commonly reported methods appear adequate for estimating firing activity within in vitro neuronal cultures, while other elements of MEA experimental design and analysis have either been underreported in the literature or investigators have employed techniques that may be inappropriate for the task. Specifically, recording duration of 20 min or longer as reported by several studies (Kuperstein et al, 2010;McConnell et al, 2012;Vincent et al, 2013;Slomowitz et al, 2015;Black et al, 2018;Feng et al, 2018), appear sufficiently long to capture the activity in individual arrays with a high degree of reproducibility. Similarly, the common practice of performing experiments with primary cultures that have been aged two to three weeks is reasonable, since the primary rat cortical cultures examined here showed a high degree of spontaneous firing by the end of the first week that plateaued through these time frames.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Spontaneous Neuronal ActivityIn VitroUsing Multi-Well Multi-Electrode Arrays: Implications for Assay Development

Negri

Menon

Young‐Pearse

2020

eNeuro

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Multi-electrode arrays (MEAs) are being more widely used by researchers as an instrument platform for monitoring prolonged, non-destructive recordings of spontaneously firing neurons in vitro for applications in modeling Alzheimer's, Parkinson's, schizophrenia, and many other diseases of the human CNS. With the more widespread use of these instruments, there is a need to examine the prior art of studies utilizing MEAs and delineate best practices for data acquisition and analysis to avoid errors in interpretation of the resultant data. Using a dataset of recordings from primary rat (Rattus norvegicus) cortical cultures, methods and statistical power for discerning changes in neuronal activity on the array level are examined. Further, a method for unsupervised spike sorting is implemented, allowing for the resolution of action potential incidents down to the single neuron level. Following implementation of spike sorting, the dynamics of firing frequency across populations of individual neurons and networks are examined longitudinally. Finally, the ability to detect a frequency independent phenotype, the change in action potential amplitude, is demonstrated through the use of pore-forming neurotoxin treatments. Taken together, this study provides guidance and tools for users wishing to incorporate multi-well MEA usage into their studies.

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Section: Discussionmentioning

confidence: 99%

Assessment of Spontaneous Neuronal ActivityIn VitroUsing Multi-Well Multi-Electrode Arrays: Implications for Assay Development

Negri

Menon

Young‐Pearse

2020

eNeuro

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“…Similarly to disease models based on genetic manipulation of healthy neuronal cultures, this approach is clearly more suitable for modeling genetic disorders. Examples of neurological disorders which have been modeled on MEAs by isolating and culturing neuronal cultures from rodents carrying specific pathogenic mutations include Autosomal Dominant Sleep-related Hypermotor Epilepsy (ADSHE) [228,255] (formerly known as Autosomal Dominant Nocturnal Frontal Lobe Epilepsy, ADNFLE), Epilepsy Aphasia Syndromes (EAS) [235], PCDH19-Clustering Epilepsy (PCDH19-CE) [234], ASD [237], FXS [240,241], and Niemann-Pick Type C1 (NPC1) disease [242].…”

Section: Disease Modelingmentioning

confidence: 99%

“…Once established, MEA-based disease models can be used as a point of reference for phenotypic rescue experiments using genetic interventions or other pharmacological and non-pharmacological treatments. Indeed, in the majority of the studies cited in the previous paragraph, researchers took advantage of their newly established disease models on MEAs to test both well-known and candidate treatments strategies aiming to improve, or ideally reverse, the pathophysiological phenotype as defined by the analysis of MEA recordings [148,158,223,225,228,241,242].…”

Section: Drug Studiesmentioning

confidence: 99%

The potential of in vitro neuronal networks cultured on micro electrode arrays for biomedical research

2023

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In vitro neuronal models have become an important tool to study healthy and diseased neuronal circuits. The growing interest of neuroscientists to explore the dynamics of neuronal systems and the increasing need to observe, measure and manipulate not only single neurons but populations of cells pushed for technological advancement. In this sense, Micro-Electrode Arrays (MEAs) emerged as a promising technique, made of cell culture dishes with embedded micro-electrodes allowing non-invasive and relatively simple measurement of the activity of neuronal cultures at the network level.In the past decade, MEAs popularity has rapidly grown. MEAs devices have been extensively used to measure the activity of neuronal cultures mainly derived from rodents. Rodent neuronal cultures on MEAs have been employed to investigate physiological mechanisms, study the effect of chemicals in neurotoxicity screenings, and model the electrophysiological phenotype of neuronal networks in different pathological conditions. With the advancements in human induced pluripotent stem cells (hiPSCs) technology, the differentiation of human neurons from the cells of adult donors became possible. hiPSCs-derived neuronal networks on MEAs have been employed to develop patient-specific in vitro platforms to characterize the pathophysiological phenotype and to test drugs, paving the way towards personalized medicine.In this review, we first describe MEAs technology and the information that can be obtained from MEAs recordings. Then, we give an overview of studies in which MEAs have been used in combination with different neuronal systems (i.e., rodent 2D and 3D neuronal cultures, organotypic brain slices, hiPSCs-derived 2D and 3D neuronal cultures, and brain organoids) for biomedical research, including physiology studies, neurotoxicity screenings, disease modeling, and drug testing. We end by discussing potential, challenges and future perspectives of MEAs technology, and providing some guidance for the choice of theneuronal model and MEAs device, experimental design, data analysis and reporting for scientific publications.

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“…Microelectrode arrays (MEAs) technology is a well-established tool to study how cellular composition, connectivity, genetic, and epigenetic expression correlate with the functional electrical activity expressed by in-vitro neuronal models [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. MEAs applicability ranges from drug/toxicological screening [ 1 , 5 , 9 ] to the characterization of various neuronal disorders [ 3 , 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. In particular, with the introduction of human-induced pluripotent stem cells (hiPSCs) and differentiation protocols, human-derived neuronal models could be created, potentially making the in-vitro approach more reliable and representative of in-vivo conditions.…”

Section: Introductionmentioning

confidence: 99%

Human-Derived Cortical Neurospheroids Coupled to Passive, High-Density and 3D MEAs: A Valid Platform for Functional Tests

et al. 2023

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With the advent of human-induced pluripotent stem cells (hiPSCs) and differentiation protocols, methods to create in-vitro human-derived neuronal networks have been proposed. Although monolayer cultures represent a valid model, adding three-dimensionality (3D) would make them more representative of an in-vivo environment. Thus, human-derived 3D structures are becoming increasingly used for in-vitro disease modeling. Achieving control over the final cell composition and investigating the exhibited electrophysiological activity is still a challenge. Thence, methodologies to create 3D structures with controlled cellular density and composition and platforms capable of measuring and characterizing the functional aspects of these samples are needed. Here, we propose a method to rapidly generate neurospheroids of human origin with control over cell composition that can be used for functional investigations. We show a characterization of the electrophysiological activity exhibited by the neurospheroids by using micro-electrode arrays (MEAs) with different types (i.e., passive, C-MOS, and 3D) and number of electrodes. Neurospheroids grown in free culture and transferred on MEAs exhibited functional activity that can be chemically and electrically modulated. Our results indicate that this model holds great potential for an in-depth study of signal transmission to drug screening and disease modeling and offers a platform for in-vitro functional testing.

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Improvement of impaired electrical activity in NPC1 mutant cortical neurons upon DHPG stimulation detected by micro-electrode array

Cited by 8 publications

References 57 publications

Assessment of Spontaneous Neuronal ActivityIn VitroUsing Multi-Well Multi-Electrode Arrays: Implications for Assay Development

Assessment of Spontaneous Neuronal ActivityIn VitroUsing Multi-Well Multi-Electrode Arrays: Implications for Assay Development

The potential of in vitro neuronal networks cultured on micro electrode arrays for biomedical research

Human-Derived Cortical Neurospheroids Coupled to Passive, High-Density and 3D MEAs: A Valid Platform for Functional Tests

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