Intraspinal microstimulation induced respiratory phase resetting

Abstract

Electrical stimulation of the spinal cord can activate somatic motor circuits after spinal cord injury. In particular, stimulation of the dorsal spinal cord has translated into clinical use due to the relatively low invasiveness. Modeling studies indicate that dorsal activation of motor pathways occurs through excitation of afferent projections to spinal motor pools. However, because spinal stimulation does not always allow for activation of discrete neuronal populations, off target effects are often observed. In ongoing studies, our group is investigating intraspinal microstimulation as a tool to activate respiratory motoneurons with possible application to spinal cord injury. Currently it is unclear if and how intraspinal stimulation will alter the pattern of respiratory output produced by the brainstem. However, activation of ascending respiratory‐related afferent fibers in cervical dorsal white matter or spinobulbar projections from cervical interneurons has the potential to modulate the respiratory pattern. Here we tested the hypothesis that intraspinal microstimulation in the dorsal but not ventral mid‐cervical spinal cord would rapidly alter the timing of inspiratory discharge. Diaphragm, external intercostal, and sternocleidomastoid electromyography activity was recorded in N=6 anesthetized and ventilated spinal intact adult rats. Following unilateral laminectomy from C2‐T1 a 10×2 grid was established by dividing the rostrocaudal exposed cord into ten sites with the two stimulus tracts located 0.5 and 1mm lateral to midline. A tungsten electrode was gradually advanced from the dorsal spinal surface to depth of 1800–2400μm with 10–90 μA currents (0.3 ms per phase, biphasic pulses) delivered every 600 μm. Dorsal stimulation (average simulation depth of 478 μm) resulted in an abrupt increase in respiratory rate (breaths per minute) at~13% of tested sites. Of the sites that triggered increases in respiratory rate, 54% were located at the dorsal surface (i.e., depths of 0 μm). These initial results indicate that intraspinal stimulation of the dorsal cervical spinal cord can trigger rapid changes in respiratory rate, presumably via activation of ascending pathways which innervate brainstem respiratory neurons.Support or Funding InformationFUNDING: 1R01NS080180‐01A1 (DDF), NICHD: T32‐HD043730 (MDS), Department of Defense W81XWH‐14‐1‐0625 (PJR)