Motoneuron glutamatergic receptor expression following recovery from cervical spinal hemisection

Cervical spinal hemisection at C2 (SH) removes premotor drive to phrenic motoneurons located in segments C3-C5 in rats. Spontaneous recovery of ipsilateral diaphragm muscle activity is associated with increased phrenic motoneuron expression of glutamatergic N-methyl-D-aspartate (NMDA) receptors and decreased expression of α-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) receptors. Glutamatergic receptor expression is regulated by tropomyosin related kinase receptor subtype B (TrkB) signaling in various neuronal systems and increased TrkB receptor expression in phrenic motoneurons enhances recovery post-SH. Accordingly, we hypothesized that recovery of ipsilateral diaphragm muscle activity post-SH, whether spontaneous or enhanced by adeno-associated virus (AAV)-mediated upregulation of TrkB receptor expression, is associated with increased expression of glutamatergic NMDA receptors in phrenic motoneurons. Adult male Sprague-Dawley rats underwent diaphragm EMG electrode implantation and SH surgery. Rats were injected intrapleurally with AAV expressing TrkB or GFP at 3 weeks before SH. At 14 days post-SH, the proportion of animals displaying recovery of ipsilateral diaphragm activity increased in AAV-TrkB treated (9/9) compared to untreated (3/5) or AAV-GFP treated animals (4/10; p < 0.027). Phrenic motoneuron NMDA NR1 subunit mRNA expression was ∼4-fold greater in AAV-TrkB vs. AAV-GFP treated SH animals (p < 0.004) and in animals displaying recovery vs. those not recovering (p < 0.005). Phrenic motoneuron AMPA GluR2 subunit mRNA expression decreased after SH and albeit increased in animals displaying recovery vs. those not recovering, levels remained lower than control. We conclude that increased phrenic motoneuron expression of glutamatergic NMDA receptors is associated with spontaneous recovery after SH and enhanced recovery following AAV-TrkB treatment. This article is protected by copyright. All rights reserved.