Abstract only
Reduced respiratory neural activity in ventilated rats elicits rebound increases in phrenic discharge once neural activity has been restored, a form of plasticity called ...inactivity‐induced phrenic motor facilitation (iPMF). We hypothesized that iPMF is associated with reduced phrenic burst‐to‐burst variability. Phrenic discharge was measured in anesthetized, vagotomized and ventilated Harlan (H) and Charles River (CR) Sprague Dawley rats exposed to a 30 min neural apnea or an equal duration of baseline conditions (time control). As expected, H rats expressed iPMF at 5 and 60 (p<0.05) min post‐apnea, whereas CR rats expressed iPMF only at 5 (p<0.05), but not 60 (p>0.05) min. Inspiratory time (Ti), expiratory time (Te) and peak area variability was assessed using Poincare plot analyses for burst n vs burst n+1 before, and 5 and 60 min post‐apnea. In H rats exposed to a neural apnea, standard deviations of the Poincare plot (SD1, SD2) for Ti and Te were significantly decreased at 5 and 60 min post‐apnea (p< 0.01). In CR rats exposed to a neural apnea, decreases in SD1 and SD2 for Ti and Te were observed at 5 (p<0.01), but not 60 (p>0.05) min post‐apnea. No changes in SD1 or SD2 for Ti or Te were observed in time controls (p>0.05), and no changes in SD1 or SD2 for peak area were observed in any group (p>0.05). These data suggest that iPMF is associated with decreased variability in Ti and Te. NIH
HL105511
and UW‐Madison Regent Scholars Fund
Neuroplasticity is an important property of the neural network subserving respiratory control. In a system that must maintain a minimum level of regular rhythmic activity to sustain life, it is ...perhaps not surprising that reduced respiratory neural activity (e.g. neural apnea) elicits plasticity in respiratory motor output. In ventilated rats, phrenic nerve burst amplitude (the neural correlate of tidal volume) is increased following a reversible period of neural apnea; a form of spinal plasticity called inactivity-induced phrenic motor facilitation (iPMF). The goals of this thesis were to build on our understanding of the properties, cellular mechanisms, and significance of inactivity induced respiratory plasticity. We found that: 1) spinal TNFα is necessary and sufficient to give rise to iPMF via an atypical PKC (aPKC)-dependent mechanism; 2) intrpleural injection of siRNA targeting PKCζ impairs iPMF, suggesting PKCζ is necessary within phrenic motor neurons for iPMF; 3) iPMF is sensitive to the pattern of respiratory neural inactivity, but inactivity-induced hypoglossal motor facilitation (iHMF) is not; 4) the spinal mechanisms initiating iPMF are dependent on the pattern of inactivity since a single prolonged neural apnea elicits TNFα-dependent and protein synthesis-independent iPMF, whereas iPMF elicited by intermittent neural apnea is TNFα-independent and protein synthesis-dependent; however, mechanisms of iPMF converge on aPKC since iPMF elicited by both prolonged and intermittent neural apnea requires aPKC; 6) inactivity-induced respiratory plasticity is differentially expressed among phrenic, hypoglossal, and intercostal inspiratory motor pools; and 7) the magnitude of iPMF is correlated with a proportional decrease in the apneic threshold, suggesting that expression of iPMF may stabilize breathing by reducing the apneic threshold, thereby making subsequent apneas less likely. Collectively, the studies described in this thesis expand our understanding of iPMF and provide insights for a functional role of inactivity-induced respiratory plasticity. We hypothesize that this novel property of respiratory control functions to stabilize breathing during conditions associated with sustained or intermittent reductions in respiratory neural activity such as spinal cord injury or central sleep apnea, respectively.
PDF
