Mapping neuronal networks activity of in-vitro cell cultures with microelectrode array (MEA) based systems, providing a spatial resolution down to cellular/sub-cellular levels and an adequate temporal resolution for resolving action potential propagation in both micro- and macro-circuitry, can not be achieved with the conventional implementation. New technological approaches for managing high-density electrode arrays, i.e. at least separations down to cellular dimensions, and for handling a large amount of channels, i.e. several thousands, are required. After evaluating the spatiotemporal resolutions requirements with custom designed MEAs on neuronal culture preparations, an approach based on image/video concepts reflected by both hardware and data management implementations is presented here. Our platform enables the high-resolution acquisition (full frame or zoomed), from arrays of 4096 microelectrodes integrated with separations of 21 μm and with temporal resolutions down to 10 μs, opening thus new perspectives for neuronal networks activity analysis.