Microelectrode arrays (MEAs)-based neuronal interfaces allow monitoring and stimulating neuronal networks both in vivo and in vitro. In vitro methodology is widely used to study and model at intermediate complexity learning and memory processes within a large neuronal network. Currently, commercially available MEA platforms for in vitro electrophysiology allow concurrent recording from at most 256 electrodes. However, dissociated neuronal cultures can consist of up to 100'000 cells within a monitored area of a few square millimeters. Thus, substantial spatial subsampling compromises the continuous observation of a large-scale network down to the cellular level. This book demonstrates a new concept for a system that can monitor large dissociated neuronal cultures with 4096 electrodes at high spatial resolutions. The specific objectives are (i) the design of a complete large-scale and high-resolution MEA platform and (ii) the investigation and development of wavelet- and image-based strategies to manage the large data streams with respect to real-time neurophysiological analysis.