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Single\u2010cell electrophysiology enables direct investigation of neuronal excitability, ion\u2010channel dynamics, and synaptic transmission with high temporal precision, which is crucial in understanding neuronal circuitries and how they are affected in diseases. Microelectrode arrays (MEAs) have emerged as powerful platforms enabling long\u2010term, parallel, and non\u2010invasive extracellular measurements. The advent of complementary\u2010metal\u2010oxide\u2010semiconductor (CMOS)\u2010based and high\u2010density microelectrode arrays (HD\u2010MEAs) has expanded the spatial and temporal resolution attainable both in vitro and ex vivo. Combined with acute slices, novel cell\u2010culture approaches and three\u2010dimensional (3D) brain organoids, these tools now expedite translational research in disease modeling, neurotoxicity, and pharmacology. Here, we summarise the significance of single\u2010cell electrophysiology, the advantages of the MEA systems, and the latest biomedical and technological advances in this area of research.<\/jats:p>","DOI":"10.1111\/febs.70552","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T13:31:18Z","timestamp":1776778278000},"page":"5686-5695","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bringing cellular clarity to the cortical component of\n                    <scp>ALS<\/scp>\n                    with a high\u2010density multi\u2010electrode array system"],"prefix":"10.1111","volume":"293","author":[{"given":"Zehra Yagmur","family":"Erol","sequence":"first","affiliation":[{"name":"Department of Neurology, Feinberg School of Medicine Northwestern University  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Quintanilla","sequence":"additional","affiliation":[{"name":"Department of Neurology, Feinberg School of Medicine Northwestern University  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4125-6013","authenticated-orcid":false,"given":"P. 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