Soft Depth Neural Probes Enable Chronic Recordings from the Rat Brainstem

Implanted microelectrodes offer a direct method for electrically interfacing with individual neurons in vivo. A major challenge preventing long-term deployment of such interfaces is the degradation of recording quality over time. This is especially evident when targeting deep brain structures, as surgical access is challenging and invasive, and depth probes are subjected to elevated levels of micro-motion. To address these challenges, miniaturization and biomimetic softness are emerging as effective strategies to improve stability and biointegration of neural implants. Here, we propose a penetrating probe design that couples the miniaturization, contact density, and manufacturability of microfabricated electrode arrays on flexible polyimide, with a micrometric soft-shell encapsulation. The latter leverages a zwitterionic hydrogel coating to achieve tissue-level mechanics and an anti-fouling surface. We design, develop, and validate a surgical insertion strategy and the associated tooling, enabling implantation of soft depth probes in the gigantocellular (Gi) nucleus of a rat model. We show stable, high signal-to-noise ratio neurophysiological recordings for at least 8 weeks. We further demonstrate a multimodal system to study the cortico-brainstem circuitry in transgenic mice using optogenetic cortical neuromodulation coupled to brainstem electrophysiology. Our results demonstrate that hybrid soft-flex microfabrication technology can increase the longevity and the quality of chronic neural recordings in hard-to-reach deep neural circuits.