A nanoelectrode array for obtaining intracellular recordings from thousands of connected neurons

Abstract

Current 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.