Local reductions in synaptic inputs to the phrenic motor pool elicits atypical Protein Kinase C (aPKC) and Tumor Necrosis Factor alpha (TNFá) dependent inactivity‐induced phrenic motor facilitation

Abstract

A central neural apnea in ventilated rats elicits an aPKC and TNFα dependent form of plasticity called inactivity‐induced phrenic motor facilitation (iPMF), a rebound increase in phrenic burst amplitude that is apparent when respiratory neural activity is restored. We hypothesized that iPMF following local reductions in synaptic inputs to the phrenic pool occurs via similar mechanisms. Bilateral phrenic output was recorded in anesthetized and ventilated rats. Procaine or vehicle (~200 nl) was injected in the C2 ventrolateral funiculus (VLF) to reversibly reduce axon conduction (~25 min) on one side of the spinal cord. Procaine reduced ipsilateral (−82 + 5 %baseline, p<0.05), but not contralateral (−22 + 16 %baseline, p>0.05) phrenic amplitude. Upon axon conduction recovery, only ipsilateral phrenic amplitude was significantly increased (60 min post: ipsi: 83± 22 %baseline, p<0.01; contra: 33 + 13 %baseline, p>0.05); while no changes in ipsilateral or contralateral phrenic amplitude were observed in vehicle treated rats (10 + 6 and 6 + 8 %baseline; p>0.05). Intrathecal aPKC inhibitor (ZIP) or TNFα scavenger (sTNFR1) blocked ipsilateral iPMF (60min: 24 + 11 and 16 + 7 %baseline, respectively, p>0.05). These data suggest that iPMF induced by local reductions in descending synaptic inputs to the phrenic pool require similar cellular pathways as iPMF following global reductions in respiratory neural activity. NIH HL105511