Submitted on October 31, 2008
Revised on June 5, 2009
Accepted on June 28, 2009
Locomotor-activated neurons of the cat. I. Serotonergic innervation and co-localization of 5-HT7, 5-HT2A and 5-HT1A receptors in the thoraco-lumbar spinal cord
Brian R Noga1*, Dawn M.G. Johnson2, Mirta I. Riesgo3, and Alberto Pinzon4
1 University of Miami School of Medicine
2 National Institute of Mental Health
3 University of Miami
4 Albert Einstein College of Medicine of Yeshiva University
* To whom correspondence should be addressed. E-mail: bnoga{at}miami.edu.
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-HT2A/5-HT1A 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 L3-7. 5-HT7 receptor immunoreactivity was observed on cells across the thoraco-lumbar segments (T7-L7), in a dorso-ventral gradient. Most locomotor-activated cells co-localized with 5-HT7, 5-HT2A and 5-HT1A 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-HT2A and 5HT1A receptors, respectively, with no rostrocaudal gradient. These results indicate that serotonergic modulation of locomotion likely involves 5-HT7/5-HT2A/5-HT1A receptors located on the soma and proximal dendrites of serotonergic-innervated locomotor-activated neurons within laminae VII and VIII of thoraco-lumbar segments.
