The development of microelectrode array (MEA) technology, interfaced with low-noise, high-gain analog conditioning circuits, has become a pillar for evaluating the electrophysiological properties of neurons in vitro. Simultaneous, parallel access to the activity of large neural populations within a network is essential for investigating information processing, learning, and the emergence of collective behavior. The unique ability of in vitro cultures to self-organise into functional synaptic networks over weeks, combined with MEA-based recording, has opened pathways toward active, bidirectional bio-hybrid interfaces, with demonstrations ranging from pharmacological screening to goal-directed behaviour in simulated environments. Scaling these systems to many recording channels introduces compounding challenges at every layer.