Functional assessment of in vitro neuronal networks-of relevance for disease modelling and drug testing-can be performed using multi-electrode array (MEA) technology. However, the handling and... Show moreFunctional assessment of in vitro neuronal networks-of relevance for disease modelling and drug testing-can be performed using multi-electrode array (MEA) technology. However, the handling and processing of the large amount of data typically generated in MEA experiments remains a huge hurdle for researchers. Various software packages have been developed to tackle this issue, but to date, most are either not accessible through the links provided by the authors or only tackle parts of the analysis. Here, we present ''MEA-ToolBox'', a free open-source general MEA analytical toolbox that uses a variety of literature-based algorithms to process the data, detect spikes from raw recordings, and extract information at both the single-channel and array-wide network level. MEA-ToolBox extracts information about spike trains, burst-related analysis and connectivity metrics without the need of manual intervention. MEA-ToolBox is tailored for comparing different sets of measurements and will analyze data from multiple recorded files placed in the same folder sequentially, thus considerably streamlining the analysis pipeline. MEA-ToolBox is available with a graphic user interface (GUI) thus eliminating the need for any coding expertise while offering functionality to inspect, explore and post-process the data. As proof-of-concept, MEA-ToolBox was tested on earlier-published MEA recordings from neuronal networks derived from human induced pluripotent stem cells (hiPSCs) obtained from healthy subjects and patients with neurodevelopmental disorders. Neuronal networks derived from patient's hiPSCs showed a clear phenotype compared to those from healthy subjects, demonstrating that the toolbox could extract useful parameters and assess differences between normal and diseased profiles. Show less
Dehghani, A.; Phisonkunkasem, T.; Ozcan, S.Y.; Dalkara, T.; Maagdenberg, A.M.J.M. van den; Tolner, E.A.; Karatas, H. 2021
Neuroinflammatory changes involving neuronal HMGB1 release and astrocytic NF-KB nuclear translocation occur following cortical spreading depolarization (CSD) in wildtype (WT) mice but it is unknown... Show moreNeuroinflammatory changes involving neuronal HMGB1 release and astrocytic NF-KB nuclear translocation occur following cortical spreading depolarization (CSD) in wildtype (WT) mice but it is unknown to what extent this occurs in the migraine brain. We therefore investigated in familial hemiplegic migraine type 1 (FHM1) knock-in mice, which express an intrinsic hyperexcitability phenotype, the extent of neuroinflammation without and after CSD. CSD was evoked in one hemisphere by pinprick (single CSD) or topical KCl application (multiple CSDs). Neuroinflammatory (HMGB1, NF-KB) and neuronal activation (pERK) markers were investigated by immunohistochemistry in the brains of WT and FHM1 mutant mice without and after CSD. Effects of NMDA receptor antagonism on basal and CSD-induced neuroinflammatory changes were examined by, respectively, systemically administered MK801 and ifenprodil or topical MK801 application. In FHM1 mutant mice, CSD caused enhanced neuronal HMGB1 release and astrocytic NF-KB nuclear translocation in the cortex and subcortical areas that were equally high in both hemispheres. In WT mice such effects were only pronounced in the hemisphere in which CSD was induced. Neuroinflammatory responses were associated with pERK expression indicating neuronal activation. Upon CSD, contralateral cortical and striatal HMGB1 release was reduced by topical application of MK801 in the hemisphere contralateral to the one in which CSD was induced. This study reveals that neuroinflammatory activation after CSD is widespread and extends to the contralateral hemisphere, particularly in brains of FHM1 mutant mice. Effective blockade of CSD-induced neuroinflammatory responses in the contralateral hemisphere in FHM1 mice by local NMDA receptor antagonism suggests that neuronal hyperexcitability-related neuroinflammation is relevant in migraine pathophysiology, but possibly also other neurological disorders in which spreading depolarization is involved. Show less
