Increased ventral spinal TNF‐alpha following hypocapnia‐induced respiratory neural inactivity

Abstract

Respiratory‐related neural inactivity induced by hypocapnia elicits an atypical PKC‐dependent form of plasticity known as inactivity‐induced phrenic motor facilitation (iPMF). Since TNF‐alpha plays a prominent role in inactivity‐induced homeostatic plasticity in the cortex, we hypothesized that iPMF is associated with increased TNF‐alpha in spinal regions associated with the phrenic motor nucleus. Anesthetized and ventilated rats were exposed to 30 min of hypocapnia (5–10 mmHg below baseline) to reversibly deprive phrenic motor neurons of rhythmic respiratory activity. Sixty minutes after restoration of phrenic activity, ventral C3–C5 spinal segments were harvested and processed for TNF‐alpha concentration via ELISA. In rats exposed to hypocapnia, TNF‐alpha significantly increased in the ventral cervical spinal cord (44 +/− 10%; n = 3, p < 0.05) versus time control rats not exposed to hypocapnia. Increased TNF‐alpha may be specific to iPMF since preliminary data suggest increased ventral spinal TNF‐alpha does not occur with phrenic motor plasticity induced by intermittent hypoxia (i.e., phrenic LTF). We are currently investigating the requirement for TNF‐alpha receptor activation for iPMF. These preliminary data suggest a prominent role for TNF‐alpha in phrenic motor plasticity following acute neural activity deprivation (NIH HL69064).