Giulia Parodi, Martina Brofiga, Vito Paolo Pastore, Michela Chiappalone, Sergio Martinoia
{"title":"Deepening the role of excitation/inhibition balance in human iPSCs-derived neuronal networks coupled to MEAs during long-term development.","authors":"Giulia Parodi, Martina Brofiga, Vito Paolo Pastore, Michela Chiappalone, Sergio Martinoia","doi":"10.1088/1741-2552/acf78b","DOIUrl":null,"url":null,"abstract":"<p><p><i>Objective.</i>The purpose of this study is to investigate whether and how the balance between excitation and inhibition ('E/I balance') influences the spontaneous development of human-derived neuronal networks<i>in vitro</i>. To achieve that goal, we performed a long-term (98 d) characterization of both homogeneous (only excitatory or inhibitory neurons) and heterogeneous (mixed neuronal types) cultures with controlled E/I ratios (i.e. E:I 0:100, 25:75, 50:50, 75:25, 100:0) by recording their electrophysiological activity using micro-electrode arrays.<i>Approach.</i>Excitatory and inhibitory neurons were derived from human induced pluripotent stem cells (hiPSCs). We realized five different configurations by systematically varying the glutamatergic and GABAergic percentages.<i>Main results.</i>We successfully built both homogeneous and heterogeneous neuronal cultures from hiPSCs finely controlling the E/I ratios; we were able to maintain them for up to 3 months. Homogeneity differentially impacted purely inhibitory (no bursts) and purely excitatory (few bursts) networks, deviating from the typical traits of heterogeneous cultures (burst dominated). Increased inhibition in heterogeneous cultures strongly affected the duration and organization of bursting and network bursting activity. Spike-based functional connectivity and image-based deep learning analysis further confirmed all the above.<i>Significance.</i>Healthy neuronal activity is controlled by a well-defined E/I balance whose alteration could lead to the onset of neurodevelopmental disorders like schizophrenia or epilepsy. Most of the commonly used<i>in vitro</i>models are animal-derived or too simplified and thus far from the<i>in vivo</i>human condition. In this work, by performing a long-term study of hiPSCs-derived neuronal networks obtained from healthy human subjects, we demonstrated the feasibility of a robust<i>in vitro</i>model which can be further exploited for investigating pathological conditions where the E/I balance is impaired.</p>","PeriodicalId":16753,"journal":{"name":"Journal of neural engineering","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of neural engineering","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1088/1741-2552/acf78b","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Objective.The purpose of this study is to investigate whether and how the balance between excitation and inhibition ('E/I balance') influences the spontaneous development of human-derived neuronal networksin vitro. To achieve that goal, we performed a long-term (98 d) characterization of both homogeneous (only excitatory or inhibitory neurons) and heterogeneous (mixed neuronal types) cultures with controlled E/I ratios (i.e. E:I 0:100, 25:75, 50:50, 75:25, 100:0) by recording their electrophysiological activity using micro-electrode arrays.Approach.Excitatory and inhibitory neurons were derived from human induced pluripotent stem cells (hiPSCs). We realized five different configurations by systematically varying the glutamatergic and GABAergic percentages.Main results.We successfully built both homogeneous and heterogeneous neuronal cultures from hiPSCs finely controlling the E/I ratios; we were able to maintain them for up to 3 months. Homogeneity differentially impacted purely inhibitory (no bursts) and purely excitatory (few bursts) networks, deviating from the typical traits of heterogeneous cultures (burst dominated). Increased inhibition in heterogeneous cultures strongly affected the duration and organization of bursting and network bursting activity. Spike-based functional connectivity and image-based deep learning analysis further confirmed all the above.Significance.Healthy neuronal activity is controlled by a well-defined E/I balance whose alteration could lead to the onset of neurodevelopmental disorders like schizophrenia or epilepsy. Most of the commonly usedin vitromodels are animal-derived or too simplified and thus far from thein vivohuman condition. In this work, by performing a long-term study of hiPSCs-derived neuronal networks obtained from healthy human subjects, we demonstrated the feasibility of a robustin vitromodel which can be further exploited for investigating pathological conditions where the E/I balance is impaired.
期刊介绍:
The goal of Journal of Neural Engineering (JNE) is to act as a forum for the interdisciplinary field of neural engineering where neuroscientists, neurobiologists and engineers can publish their work in one periodical that bridges the gap between neuroscience and engineering. The journal publishes articles in the field of neural engineering at the molecular, cellular and systems levels.
The scope of the journal encompasses experimental, computational, theoretical, clinical and applied aspects of: Innovative neurotechnology; Brain-machine (computer) interface; Neural interfacing; Bioelectronic medicines; Neuromodulation; Neural prostheses; Neural control; Neuro-rehabilitation; Neurorobotics; Optical neural engineering; Neural circuits: artificial & biological; Neuromorphic engineering; Neural tissue regeneration; Neural signal processing; Theoretical and computational neuroscience; Systems neuroscience; Translational neuroscience; Neuroimaging.