Long term facilitation (LTF) of ipsilateral but not contralateral phrenic motor output after C2 spinal hemisection (C2HS)

Abstract

After chronic C2HS, exposure to intermittent hypoxia (IH) evokes a persistent increase in phrenic output recorded ipsilateral to the injury (i.e. LTF, Golder and Mitchell, J Neurosci. 25:2925-32, 2005). However, unilateral spinal cord injury can induce compensatory increases in contralateral motoneuron activity that may reduce their capacity for further plasticity (i.e. a “ceiling effect”). We hypothesized that after chronic C2HS, LTF would be reduced in contralateral (vs. ipsilateral) phrenic output. Bilateral phrenic activity was recorded in three groups of anesthetized, paralyzed, vagotomized and ventilated rats: uninjured control (N=7), and four (N=8) or eight wks (N=6) post-C2HS. All C2HS lesions were histologically verified. Stable baseline (BL) phrenic activity was established during normoxia, after which rats were exposed to IH (3x5 min isocapnic hypoxia; FIO2=0.13–0.14), and then returned to isocapnic normoxia. LTF was assessed 60-min post-IH. Uninjured control animals showed burst amplitude LTF that was similar in the left (44±11 %BL) and right phrenic nerves (39±13 %BL). However, LTF was not observed in phrenic burst amplitude recorded contralateral to C2HS at four (−16±7 %BL) or eight wks post-C2HS (−10±16 % BL). In contrast, LTF of ipsilateral phrenic amplitude occurred at both four (45±11 % BL) and eight wks post-C2HS (157±57 % BL, p<0.05). A persistent increase in phrenic burst frequency after IH (i.e. “frequency LTF”) was observed in control (+9±3 burst/min, p<0.05), but not C2HS rats. We conclude that brief IH does not induce LTF of phrenic motor output contralateral to chronic C2HS injury. Supported by the Christopher Reeve Foundation and the American Paraplegia Society.