The objective of this program is to define a hierarchical integration architecture that allows all the heterogeneous components required for electrical and optical interface with neurons can be directly integrated on a micromachined probe substrate with a low-rise profile for high-density studies of neural networks in behaving animals. The implemented microsystem aims to be a generic platform technology for scalable, adaptable and reconfigurable hybrid integration. The intellectual merit is in a number of important areas, including the formation of highdensity interconnects to hybrid electronic chips, hermetic encapsulation of these chips on micromachined platforms, the use of magnetically-aligned anisotropic conductive adhesives for high-density lead transfers, the monolithic integration of highly-flexible parylene cables into probes formed using completely dry-etched process flows, and the development of hermetic, low-profile packages that are compatible with both the cables and the hybrid circuitry. The broader impacts are in realizing tools to permit revolutionary progress in our understanding of neural circuits and systems. The work will also provide a platform for realizing improved prostheses designed to overcome disorders such as severe epilepsy, Parkinson?s disease, and, perhaps, paralysis. Though important these breakthroughs in health care will be, the impact of the work should be much broader, especially in combining MEMS-based sensors with embedded computing and wireless connectivity, as the next major frontier in microelectronics, coupling it to the non-electronic world.