Modulation of phrenic motoneuron plasticity following chronic high cervical spinal cord injury in the rat

Abstract

Hypoxia-induced short term potentiation (STP) of respiratory output represents a progressive increase in activity following the acute response and a gradual decrease in activity upon termination of hypoxia. Evidence supports a spinal mechanism for phrenic STP, and we hypothesized that a chronic spinal cord lesion which may increase phrenic motoneuron (PMN) excitability would enhance phrenic STP. Bilateral phrenic activity was recorded in anesthetized and vagotomized rats with chronic cervical (C2) hemilesion (C2HS). STP induced by hypoxia (PaO2~40 mmHg) was significantly greater in ipsilateral (IL) compared with contralateral phrenic output. We next used a single fiber recording approach to measure IL PMN bursting. PMNs were classified as early-inspiratory (Early-I), late-inspiratory (Late-I), or silent according to their discharge pattern during baseline (PaO2~210 mmHg, PaCO2~37 mmHg). Hypoxia increased the discharge frequency of both Early-I and Late-I PMNs in C2HS and control rats as expected. However, the relative proportion of silent PMNs that became active during hypoxia was substantially greater in C2HS (23/38, 61%) than control rats (9/32, 28%). In addition, silent PMNs exhibited post-hypoxia STP of burst frequency in C2HS but not control rats. We conclude that the enhanced phrenic STP after chronic C2HS reflects an increase in the recruitment of silent PMNs during and following hypoxia.