Spinal cord hemisection disrupts descending neuregulin input to phrenic motoneurons

Abstract

Spinal cord hemisection at C2 (SH) disrupts descending drive to ipsilateral phrenic motoneurons (PMNs) causing unilateral diaphragm muscle (DIAm) paralysis. Previously, we found a decrease in motoneuron size at 2 weeks post‐SH. Recently, we found neuregulin (NRG) in synaptic boutons surrounding PMNs. NRG is a trophic factor known to regulate development of the neuromuscular junction, but the effect of NRG on motoneurons is unknown. We hypothesized that 1) NRG input to PMNs is supraspinal in origin, and 2) SH disrupts NRG input to PMNs. Adult male Sprague‐Dawley rats underwent SH or sham‐surgery. PMNs were retrogradely labeled by intramuscular injection of Alexa488‐conjugated cholera toxin B. Using laser capture microdissection, we found that PMNs express mRNA for the NRG receptors ErbB2 and ErbB3, providing a functional substrate for a NRG effect. Two weeks post‐SH, labeled PMNs and NRG boutons were imaged using confocal microscopy. PMN morphology and the number of NRG boutons in the vicinity of PMNs were determined using a computerized, semi‐automated reconstruction algorithm. NRG boutons were fairly homogeneously distributed on motoneurons independent of size. Following SH, few NRG boutons were observed. We conclude that 1) NRG input to PMNs derives from a supraspinal source; and 2) SH removes NRG input to PMNs. It is possible that NRG input exerts a trophic influence on PMNs.Supported by NIH grants HL37680, AR51173 and Mayo Clinic