Intracellular microelectrode array (iMEA) and synaptic connectivity mapping

– Intracellular recording offers exquisite access to the electrical interior of a neuron––detecting not only spikes but also the small synaptic signals that reflect synaptic connections and their properties––but it had been limited to only one cell at a time. In 2020, a CMOS nanoelectrode array broke this constraint and massively parallelized intracellular recording, opening a path to capturing synaptic signals across a neuronal network. This shift led us in 2021 to propose the copy framework: population-scale intracellular recording is a process of copying a biological network, because the resulting data––rich with synaptic signals from across the network––reveal its synaptic connectivity map. In this Perspective , we revisit that framework because the recent CMOS intracellular microelectrode array (iMEA), building on the 2020 nanoelectrode array, transforms copy from a demanding demonstration into a practical, high-yield technology. By routinely recording intracellular signals across thousands of neurons, the iMEA uncovers synaptic organization with a breadth and clarity previously unreachable. We outline the development of the iMEA as an improved copy platform, what it now enables, and what must still be advanced to build a richer synaptic connectivity map––one that is indispensable to understanding how the brain functions, and provides a firmer foundation for neuromorphic models grounded in the brain’s own wiring.