Spinal cord injury studies use the presence of serotonin (5-HT)-immunoreactive axons caudal to the injury site as evidence of axonal regeneration. As olfactory ensheathing glia (OEG) transplantation improves hindlimb locomotion in adult rats with complete spinal cord transection, we hypothesized that more 5-HT-positive axons would be found in the caudal stump of OEG-than media-injected rats. Previously we found 5-HT-immunolabeled axons that spanned the transection site only in OEGinjected rats but detected labeled axons just caudal to the lesion in both media-and OEG-injected rats. Now we report that many 5-HT-labeled axons are present throughout the caudal stump of both media-and OEG-injected rats. We found occasional 5-HT-positive interneurons that are one likely source of 5-HT-labeled axons. These results imply that the presence of 5-HT-labeled fibers in the caudal stump is not a reliable indicator of regeneration. We then asked if 5-HT-positive axons appose cholinergic neurons associated with motor functions: central canal cluster and partition cells (active during fictive locomotion) and somatic motor neurons (SMNs). We found more 5-HT-positive varicosities in lamina X adjacent to central canal cluster cells in lumbar and sacral segments of OEGthan media-injected rats. SMNs and partition cells are less frequently apposed. As nonsynaptic release of 5-HT is common in the spinal cord, an increase in 5-HT-positive varicosities along motorassociated cholinergic neurons may contribute to the locomotor improvement observed in OEGinjected spinal rats. Furthermore, serotonin located within the caudal stump may activate lumbosacral locomotor networks. J. Comp. Neurol. 515: 664-676, 2009.
Indexing termsplasticity; locomotion; OEG; spinal cord injury; 5-HT; ChAT; cholinergic neurons Adult cats and neonatal rats with completely transected spinal cords (i.e., spinal animals) can be trained to generate fairly coordinated patterns of hindlimb stepping on the treadmill in the absence of supraspinal connections (Lovely et al., 1986;Barbeau et al., 1987;de Leon et al., 1998;Joynes et al., 1999;Jordan and Schmidt, 2002;Edgerton et al., 2004;Kubasak et al., 2005). In contrast, adult spinal rats do not demonstrate coordinated locomotor stepping without therapeutic interventions. Electrical and/or pharmacological interventions, including serotonin (5-HT) receptor agonists that likely activate central pattern generation in the lumbosacral cord, can facilitate bipedal stepping in adult spinal rats (Ichiyama et al., 2005;Lavrov et al., 2006;Gerasimenko et al., 2007). In addition to evidence from in vivo studies, in vitro neonatal models showed that 5-HT is involved in the alternating firing of the contralateral neural networks to *Correspondence to: Patricia E. Phelps, PhD, Dept. of Physiological Science, UCLA, Box 951606, Los Angeles, CA 90095-1606. pphelps@physci.ucla.edu.
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NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript elicit bilateral locomotor-like activity (Cazalets et al., ...