Serotoninergic and nonserotoninergic neurons in the medullary raphe system have axon collateral projections to autonomic and somatic cell groups in the medulla and spinal cord

Abstract

Fluorescent double retrograde-tracing studies combined with fluorescent immunostaining for serotonin were carried out to determine the potential patterns of divergence in axonal projections to autonomic and somatic motor sites from medullary raphe and parapyramidal neurons. Injections (20-60 nl) of combinations of fluorescent retrograde tracers (Fast Blue, fluoro-gold, green latex microspheres, Diamidino Yellow) were made into the intermediolateral cell column (IML) of the spinal cord and the brainstem lateral tegmental field or ventral horn of the lumbar spinal cord of male Wistar rats. The animals were perfused after a 7-10-day survival period, and the brains were removed, sectioned (50 microns), and immunostained for serotonin. Following injections of different retrograde-tracer substances into the IML of the thoracic cord and the ventral horn of the lumbar cord, 36% of the neurons with axon collateral projections to the IML and the lumbar ventral horn were serotoninergic. Following injections of different retrograde-tracer substances into the IML and the lateral tegmental field, 26% of the neurons with axon collateral projections to the IML and the lateral tegmental field were serotoninergic. Many of the medullary neurons with projections to the lateral tegmental field and the lumbar cord were located dorsal and lateral to those neurons with projections to the IML. The results indicate that serotoninergic and nonserotoninergic neurons of the midline raphe system and parapyramidal region have axon collateral branches to the IML and the lateral tegmental field or the IML and the lumbar ventral horn. These projection neurons may form the anatomical substrate for the integration of autonomic and somatic motor activity.

Activity of Serotonergic Neurons in Behaving Animals

“…Third, there is evidence that spinally projecting medullary 5-HT neurons collateralize at various levels of the cord, suggesting a broad relationship to motor output (Skagerberg and Bjorklund 1985). Fourth, the fact that single medullary 5-HT neurons may project to both the intermediolateral column of the spinal cord as well as to the ventral horn suggests an integrative function involving motor and autonomic control (Allen and Cechetto 1994).…”

Conditional Sox9 ablation reduces chondroitin sulfate proteoglycan levels and improves motor function following spinal cord injury

“…Serotonergic projections synapsing in the dorsal horn modulate pain sensation (Bardin et al, 2000;Calejesan et al, 1998), serotonergic projections targeting sympathetic preganglionic neurons in the intermediolateral cell column (IML) contribute to autonomic regulation (Allen and Cechetto, 1994), and serotonergic projections synapsing in the ventral horn provide excitatory input to motor neurons, the loss of which correlates with locomotor dysfunction (Saruhashi et al, 1996). To evaluate whether the improved recovery achieved by the Sox9 conditional knock-out mice could be attributed to increased 5-HT inputs onto targets caudal to the injury we performed immunostaining for 5-HT on crosssections from Sox9 conditional knock-outs and controls 14 weeks after SCI.…”

C3 peptide enhances recovery from spinal cord injury by improved regenerative growth of descending fiber tracts

“…Moreover, serotonergic input to lumbar -motoneurons of the ventral horn was enhanced to a similar degree by the peptide. In the mammalian spinal cord, the predominant role of 5HT, which mainly originates from medullary raphe nuclei, seems to be the facilitation of motor performance as well as the coordination between motor, autonomic and sensory systems (Skagerberg and Björklund, 1985;Allen and Cechetto, 1994;Kim et al, 2004;Boido et al, 2009). Our findings of improved serotonergic input to lumbar motoneurons, thus, provide strong evidence for one probable mechanism that leads to enhanced functional recovery in mice treated with C3bot .…”