Platinized graphene fiber electrodes revealed differential activity in terminal splenic neurovascular plexi supporting a direct spleen-vagus communication

Neural interfacing nerve fascicles along the splenic neurovascular plexi (SNVP) is needed to better understand the spleen physiology, and for selective neuromodulation of this major organ. However, the small size and anatomical location have proven to be a significant challenge. Here, we use a reduced liquid crystalline graphene oxide (rGO) fiber coated with platinum (Pt) as a super-flexible suture-like electrode to interface multiple SNVP. The Pt-rGO fibers were used as handover knot electrodes over the small plexi, allowing sensitive recording from the splenic nerve (SN) terminal branches. Asymmetric defasciculation of the SN branches was revealed by electron microscopy, and the functional compartmentalization in spleen innervation was evidenced in response to hypoxia and pharmacological modulation of mean arterial pressure. We demonstrate that electrical stimulation of cervical and subdiaphragmatic vagus nerve (VN), evoked direct activity in a subset of SN terminal branches, providing evidence for a direct VN control over the spleen. This notion was supported by tract-tracing of SN branches, revealing an unconventional direct spleen-VN projection. High-performance Pt-rGO fiber electrodes, may be used for the fine neural modulation of other small neurovascular plexi at the point of entry of the organs as a bioelectronic medical alternative.