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This Article Full Text Full Text (PDF) All Versions of this Article: 102/3/1560    most recent 91179.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Noga, B. R. Articles by Pinzon, A. PubMed PubMed Citation Articles by Noga, B. R. Articles by Pinzon, A.

Locomotor-Activated Neurons of the Cat. I. Serotonergic Innervation and Co-Localization of 5-HT₇, 5-HT_2A, and 5-HT_1A Receptors in the Thoraco-Lumbar Spinal Cord

Miami Project to Cure Paralysis, University of Miami School of Medicine, Miami, Florida

Submitted 31 October 2009; accepted in final form 28 June 2009

Abstract

Monoamines are strong modulators and/or activators of spinal locomotor networks. Thus monoaminergic fibers likely contact neurons involved in generating locomotion. The aim of the present study was to investigate the serotonergic innervation of locomotor-activated neurons within the thoraco-lumbar spinal cord following induction of hindlimb locomotion. This was determined by immunohistochemical co-localization of serotonin (5-HT) fibers or 5-HT₇/5-HT_2A/5-HT_1A receptors with cells expressing the activity-dependent marker c-fos. Experiments were performed on paralyzed, decerebrate cats in which locomotion was induced by electrical stimulation of the mesencephalic locomotor region. Abundant c-fos immunoreactive cells were observed in laminae VII and VIII throughout the thoraco-lumbar segments of locomotor animals. Control sections from the same segments showed significantly fewer labeled neurons, mostly within the dorsal horn. Multiple serotonergic boutons were found in close apposition to the majority (80–100%) of locomotor cells, which were most abundant in lumbar segments L_3–7. 5-HT₇ receptor immunoreactivity was observed on cells across the thoraco-lumbar segments (T₇–L₇), in a dorsoventral gradient. Most locomotor-activated cells co-localized with 5-HT₇, 5-HT_2A, and 5-HT_1A receptors, with largest numbers in laminae VII and VIII. Co-localization of c-fos and 5-HT₇ receptor was highest in the L₅–L₇ segments (>90%) and decreased rostrally (to 50%) due to the absence of receptors on cells within the intermediolateral nucleus. In contrast, 60–80 and 35–80% of c-fos immunoreactive cells stained positive for 5-HT_2A and 5-HT_1A receptors, respectively, with no rostrocaudal gradient. These results indicate that serotonergic modulation of locomotion likely involves 5-HT₇/5-HT_2A/5-HT_1A receptors located on the soma and proximal dendrites of serotonergic-innervated locomotor-activated neurons within laminae VII and VIII of thoraco-lumbar segments.