Abbott, JeffreyYe, TianyangKrenek, KeithGertner, Rona S.Ban, StevenKim, YoubinQin, LingWu, WenxuanPark, HongkunHam, Donhee2023-07-272019-09-23Abbott, Jeffrey, Tianyang Ye, Keith Krenek, Rona S. Gertner, Steven Ban, Youbin Kim, Ling Qin et al. "A nanoelectrode array for obtaining intracellular recordings from thousands of connected neurons." No Journal No Volume. DOI: 10.1038/s41551-019-0455-72157-846Xhttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37376628Current electrical or optical electrophysiology methods cannot reliably obtain intracellular recordings simultaneously from more than a few tens of neurons. Here, we report a nanoelectrode array that can record action potentials and post-synaptic potentials in thousands of connected mammalian neurons in vitro. The array consists of 4,096 platinum black electrodes with nanoscale roughness fabricated on top of a silicon chip that monolithically integrates 4,096 microscale amplifiers, configurable into pseudocurrent-clamp or pseudovoltage-clamp modes, that allow for concurrent current injection and voltage amplification. We used the array in pseudocurrent-clamp mode to quantify subthreshold post-synaptic potentials, and in pseudovoltage-clamp mode to measure the effects of drugs on ion-channel currents. We also mapped over 300 excitatory and inhibitory synaptic connections from about 1,700 neurons in 19 mins. This high-throughput technology could benefit functional connectome mapping, electrophysiological screening, and other functional interrogations of neuronal networks.en-USJournal Article2023-07-2710.1038/s41551-019-0455-7