The brain is a massively interconnected network of specialized circuits. Even primary sensory areas, once thought to support relatively simple, feed-forward processing, are now known to be parts of complex feedback circuits. All brain functions depend on millisecond timescale interactions across these brain networks, but current approaches cannot measure or manipulate these interactions with sufficient resolution to resolve them. We need the capacity to measure and manipulate the activity large ensembles of neurons distributed across anatomically or functionally connected circuits. That technology does not yet exist, a lack that motivates our efforts to develop a new system for large scale, multisite recording and manipulation that takes integrates biocompatible polymer electrodes, new headstage amplifiers, a new Ethernet-based data transmission system and open source, real-time cross-platform software. This system will support recordings and manipulations across thousands of channels in awake, behaving animals as well as closed loop feedback for the next generation of experiments. Our Specific Aims are 1) To develop new high-density, double-sided polymer recording/manipulation probes, 2) To develop new high-density headstage chips, integrated electrode- headstage assemblies and surgical techniques for implanting them, and 3) To develop a low-cost, powerful data acquisition system with open-source software and real-time capabilities. We have assembled a unique team of scientists and engineers with expertise spanning polymer electrode technology, integrated electronics, real-time systems, large-scale recording, and commercial experience. Our combined expertise will allow us to create and provide to the neuroscience community an integrated system that will allow for large scale, distributed measurements and manipulation of neural activity across many sites in awake, behaving animals.