Serotonergic Innervation of Cat Spinal Locomotor Neurons

Monoamines are strong modulators and/or activators of spinal locomotor networks. 21 Thus, monoaminergic fibers likely contact neurons involved in generating locomotion. The aim 22 of the present study was to investigate the serotonergic innervation of locomotor-activated 23 neurons within the thoraco-lumbar spinal cord following induction of hindlimb locomotion. This 24 was determined by immunohistochemical co-localization of serotonin (5-HT) fibers or 5-HT7/525 HT2A/5-HT1A receptors with cells expressing the activity-dependent marker c-fos. Experiments 26 were performed on paralyzed, decerebrate cats, in which locomotion was induced by electrical 27 stimulation of the mesencephalic locomotor region. Abundant c-fos immunoreactive cells were 28 observed in laminae VII and VIII throughout the thoraco-lumbar segments of locomotor animals. 29 Control sections from the same segments showed significantly fewer labeled neurons, mostly 30 within the dorsal horn. Multiple serotonergic boutons were found in close apposition to the 31 majority (80-100%) of locomotor cells, which were most abundant in lumbar segments L3-7. 532 HT7 receptor immunoreactivity was observed on cells across the thoraco-lumbar segments (T733 L7), in a dorso-ventral gradient. Most locomotor-activated cells co-localized with 5-HT7, 5-HT2A 34 and 5-HT1A receptors, with largest numbers in laminae VII and VIII. Co-localization of c-fos and 35 5-HT7 receptor was highest in the L5-L7 segments (>90%) and decreased rostrally (to ~50%) 36 due to the absence of receptors on cells within the intermediolateral nucleus. In contrast, 6037 80% and 35-80% of c-fos immunoreactive cells stained positive for 5-HT2A and 5HT1A receptors, 38 respectively, with no rostrocaudal gradient. These results indicate that serotonergic modulation 39 of locomotion likely involves 5-HT7/5-HT2A/5-HT1A receptors located on the soma and proximal 40 dendrites of serotonergic-innervated locomotor-activated neurons within laminae VII and VIII of 41 thoraco-lumbar segments. 42