Nat. Biomed. Eng. http://doi.org/dchb (2019).

Multi-electrode arrays can record from thousands of neurons, but these recordings are extracellular and do not pick up subthreshold events that allow assessment of synaptic connectivity. Such measurements have been the domain of patch-clamp electrodes, with the caveat of low throughput. Abbott et al. describe complementary metal-oxide-semiconductor (CMOS) neuroelectronic interphases (CNEI) that can intracellularly record from thousands of neurons simultaneously. The CNEIs can be operated in either pseudocurrent clamp or in pseudovoltage clamp, in analogy to the recording modes of patch-clamp electrodes. The researchers demonstrated the capabilities of their CNEIs by acquiring intracellular recordings from cultured neurons while pharmacologically manipulating the cultures. In addition, the researchers assessed synaptic connectivity at a network-wide scale. Recordings can last for several minutes and, with the ability of monitoring thousands of neurons, datasets can be acquired at unprecedented scale with the CNEI technology.