Cellular-scale silicon probes for high-density, precisely-localized neurophysiology

Neural implants with large numbers of electrodes have become an important tool for examining brain functions. However, these devices typically displace a large intracranial volume compared to the neurons they record. This large size limits the density of implants, provokes tissue reactions that degrade chronic performance, and impedes the ability to accurately visualize recording sites within intact circuits. Here we report next-generation silicon-based neural probes at cellular-scale (5x10{micro}m cross-section), with ultra-high-density packing (as little as 66{micro}m between shanks) and 64 or 256 closely-spaced recording sites per probe. We show that these probes can be inserted into superficial or deep brain structures and maintain high-quality spike recordings in freely behaving rats for many weeks. Finally, we demonstrate a slice-in-place approach for the precise registration of recording sites relative to nearby neurons and anatomical features, including striatal {micro}-opioid receptor patches. This scalable technology provides a valuable tool for examining information processing within neural circuits, and potentially for human brain-machine interfaces.