Noradrenergic Innervation of Cat Spinal Locomotor Neurons

Noradrenaline (NA) is a strong modulator and/or activator of spinal locomotor 21 networks. Thus, noradrenergic fibers likely contact neurons involved in generating locomotion. 22 The aim of the present study was to investigate the noradrenergic innervation of functionally23 related, locomotor-activated neurons within the thoraco-lumbar spinal cord. This was 24 accomplished by immunohistochemical co-localization of noradrenergic fibers using dopamine25 β-hydroxylase or NAα1A and NAα2B receptors with cells expressing the c-fos gene activity26 dependent marker Fos. Experiments were performed on paralyzed, precollicular-postmamillary 27 decerebrate cats, in which locomotion was induced by electrical stimulation of the 28 mesencephalic locomotor region. The majority of Fos labeled neurons, especially abundant in 29 laminae VII and VIII throughout the thoraco-lumbar (T13-L7) region of locomotor animals, 30 showed close contacts with multiple noradrenergic boutons. A small percentage (10-40%) of 31 Fos neurons in the T7-L7 segments showed co-localization with NAα1A receptors. In contrast, 32 NAα2B receptor immunoreactivity was observed in 70-90% of Fos cells, with no obvious 33 rostrocaudal gradient. In comparison to results obtained from our previous study on the same 34 animals, a significantly smaller proportion of Fos labeled neurons were innervated by 35 noradrenergic than serotonergic fibers, with significant differences observed for laminae VII and 36 VIII in some segments. In lamina VII of the lumbar segments, the degree of monoaminergic 37 receptor subtype/Fos co-localization examined statistically generally fell into the following order: 38 NAα2B = 5-HT2A ≥ 5-HT7 = 5-HT1A > NAα1A. These results suggest that noradrenergic modulation 39 of locomotion involves NAα1A/NAα2B receptors on noradrenergic-innervated locomotor-activated 40 neurons within laminae VII and VIII of thoraco-lumbar segments. Further study of the functional 41 role of these receptors in locomotion is warranted. 42