Ultraflexible electrodes for recording neural activity in the mouse spinal cord during motor behavior

Implantable electrode arrays are powerful tools for directly interrogating neural circuitry in the brain, but implementing this technology in the spinal cord in behaving animals has been challenging due to the spinal cord’s significant motion with respect to the vertebral column during behavior. Consequently, the individual and ensemble activity of spinal neurons processing motor commands remains poorly understood. Here, we demonstrate that custom ultraflexible 1-μm-thick polyimide nanoelectronic threads can conduct laminar recordings of many neuronal units within the lumbar spinal cord of unrestrained, freely moving mice. The extracellular action potentials have high signal-to-noise ratio, exhibit well-isolated feature clusters, and reveal diverse patterns of activity during locomotion. Furthermore, chronic recordings demonstrate the stable tracking of single units and their functional tuning over multiple days. This technology provides a path for elucidating how spinal circuits compute motor actions. [Display omitted] •Ultraflexible electrodes in the ventral laminae adapt to spinal cord motion•High SNR spikes from unrestrained, behaving mice resolve well-isolated single units•Functional tuning to hindlimb locomotion reveals diverse patterns of neural activity•Stable electrode-tissue interface enables longitudinal tracking of single units Wu et al. designed ultrathin flexible electrodes for intraspinal recording. The electrodes’ flexibility yields a stable neural interface despite spinal cord motion. In unrestrained behaving mice, the well-isolated single units reveal diverse tuning to locomotion and allow for longitudinal tracking of neurons.