Network intracellular recording and synaptic connection mapping with a microhole electrode array

Patch-clamp electrodes capture intracellular signals from few neurons, while microelectrode arrays (MEAs) record many neurons extracellularly with limited sensitivity. Bridging these approaches has been a long-standing goal. We report a 4,096-channel semiconductor microhole electrode array that records intracellularly from thousands of neurons in parallel. From over 2,000 neurons, more than 70,000 plausible synaptic connections were identified and classified as electrical, inhibitory, or excitatory, with about 5% error. This platform enables large-scale mapping of neuronal network connectivity with single-cell resolution.