Chronic reductions in synaptic inputs to the phrenic motor nucleus increases GluA2‐containing AMPA receptors

An acute disruption in descending synaptic inputs to the phrenic motor nucleus, elicits a form of spinal plasticity called inactivity‐induced phrenic motor facilitation (iPMF). iPMF is manifested as a rebound increase in phrenic amplitude that is apparent when synaptic inputs are restored. Here we tested the hypothesis that chronic withdrawal of phrenic synaptic inputs also elicits plasticity. Rats received a unilateral injection of aCSF or botulinum toxin A (BoNT/A;10ng) into the C4 phrenic motor pool. Three days post‐unilateral BoNT/A, cleaved SNAP‐25 was localized to ipsilateral C4 spinal segments, suggesting impairment of synaptic inputs. In a separate group of rats, ventral spinal segments (C3‐C5) were harvested and membrane proteins were biotinylated to determine membrane expression of GluA1/A2 receptors. No change in GluA1 was detected in spinal segments ipsilateral or contralateral to BoNT/A (ipsi: 14±15; contra: 19±10% sham; p<0.05). By contrast, membrane GluA2 expression was significantly increased in ventral segments ipsilateral, but not contralateral to BoNT/A (ipsi: 70±24; contra: 36±26% sham; p<0.05). Collectively, our data suggest that chronic withdrawal of phrenic synaptic inputs increases ipsilateral membrane expression of GluA2‐containing AMPA receptors. We hypothesize that iPMF is a compensatory mechanism to maintain respiratory motor output throughout life. NIH‐HL105511.