Optimizing ultraflexible electrodes and integrated electronics for high-resolution, large-scale intraspinal recording and modulation - Electrophysiology is a critical technology in neuroscience as a direct measure of neuronal functions. It has become routine for scientists to record and stimulate neuron populations in different brain regions in awake behaving animals, correlating activity with behavior. However, it has been insurmountable for the same electrophysiology to perform well in the spinal cord of behaving animals. For this reason, while the spinal cord is a critical site for locomotion and sensations, it remains largely a “black box” from a functional perspective, due to the lack of tools to measure and modulate spinal neurons while they are functioning. The main difficulty of doing electrophysiology in the spinal cord of behaving animals is because the cord is extremely mobile, moving and bending during behavior. Almost all existing neural electrodes, being mechanically more rigid than spinal tissues, fail to follow such movements, therefore yielding excessive noise and position drifts and lead to spinal injury or scaring in the long term. Here, we propose a suite of technologies centering around ultraflexible electrodes to address this challenge for the community. We now have preliminary data proving these probes achieved high quality single unit recording from spinal neurons of behaving mice. Markedly, when the animals are actively moving in diverse behaviors, we were still able to stably track neuron populations through spike sorting. Our preliminary long-term results also verified chronic in vivo recording for over 5 months after implantation in the spinal cord. Motivated by this success, we propose research plans to optimize this technology for spinal cord studies. Critically, we have brought together a group of outstanding neuroscientists to work with us in developing surgical approaches, and testing devices across different spinal areas, animal models, and research topics. These efforts are organized into three aims. We expect this new technology will enable new perspectives on the function of individual spinal cells in the context of a wide spectrum of behaviors that the spinal cord mediates (different speeds of locomotion, stopping, reflex withdrawal, reaching, grasping, urination, etc.). This will allow neuroscientists to connect the well-developed genetic and developmental characterization of spinal cell types to the circuit; to understand how other parts of the nervous system interact with the spinal cord. From a translational perspective, this offers the opportunity for a better understanding of the etiology and progression of spinal cord injury and disease by chronic monitoring; opens up the potential for intra-spinal interfaces that treat spinal cord injury, stroke, movement disorders, and motor neuron diseases.
