Frédéric Pierre Gérald Michoud
Diseases or injuries affecting the nervous system can dramatically disrupt the quality of life. Despite extensive efforts towards treating dysfunctional nervous systems, the pharmacological and electrical approaches generally involved lack the temporal and spatial resolutions needed to selectively modulate neural activity. The somatosensory system intertwines numerous neural populations with distinct functionalities, whose specific neuromodulation would be beneficial for the alleviation of chronic pain and the restoration of locomotion after spinal cord injury. This thesis aims to develop a new generation of electrical and optical neural interfaces to selectively parse the somatosensory system.
At the peripheral nerve level, we proposed an optical cuff and a wireless optoelectronic system to deliver epineural optogenetic stimulations in freely-behaving mice. The former consists of a soft elastomeric cuff wrapped around the sciatic nerve and integrated into a thin optic fiber. We demonstrated consistent orderly recruitment of motor units with optical stimulations in Thy1::ChR2 mice. This optocuff represents a simple, yet efficient, solution to probe the peripheral nervous system using optogenetics. However, untethered experimentation offers more versatility for fine neuromodulation applications. Within this framework, we developed a system comprising an ultra-miniaturized wireless stimulator and a soft circumneural ÎŒ-LED array to deliver optogenetic stimulations to the sciatic nerve. This optoelectronic implant conformed to the nerveâs morphology and complied with its dynamic motion. We demonstrated the systemâs efficacy via optogenetic activation of nociceptors in TRPV1::ChR2 mice. Both the optocuff and the wireless optoelectronic system exhibited seamless bio-integration after chronic implantation, thus highlighting the benefits of soft neurotechnology for interfacing with peripheral nerves.
At the spinal level, we introduced a transversal electrode array for multipolar epidural stimulation of the spinal cord. The silicone materials used for its fabrication conferred this implant with mechanical properties matching the dura mater, allowing for remarkable biocompatibility following long-term implantation. Based on the spinal cord anatomy, this implant displayed a wide distribution of neural electrodes at a single spinal level, which enabled selective recruit- ment of posterior spinal roots. This novel paradigm was implemented to a spatio-temporal stimulation protocol and demonstrated potential in restoring locomotion after spinal cord injury. Finally, we reported a soft Ό-LED array to deliver optogenetic stimulations in deep spinal structures. Insertion of this thin (< 100 Όm) optoelectronic implant in the mouse epidural space did not provoke tissue damages while maintaining its functionality with normal dynamic motion. As a proof-of-principle, we showed concomitant electromyographic activity with epidural optical stimulations in Thy1::ChR2 mice. This premise offers a large range of opportunities to probe the spinal circuits involved in sensory processing and locomotion.
In conclusion, these selective neural interfaces are proposed as innovative tools to unravel peripheral and spinal neural circuits. This venue will support the development of relevant clinical treatments for tackling dysfunctional neural systems. Eventually, these implant concepts pave the way for the translation of fine neuromodulation therapies in humans.
EPFL2019
