Neurochemical substrates of locomotor and non-locomotor rhythms in rat spinal cord

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Crowley, Kristine C.
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It has long been understood that the mammalian spinal cord is capable of generating locomotion. However, the neurochemical and anatomical substrates underlying this rhythmic behaviour remain largely unknown. Mechanisms underlying the generation and coordination of locomotion were investigated in this thesis using an in vitro neonatal rat spinal cord preparation. Part I examines whether ventral root activity reliably indicates the presence of flexor and extensor activity in the in vitro rat spinal cord preparation. Ventral root patterns recorded during locomotion and ventral root transection experiments indicated that ankle flexor and extensor nerve activity depended on motor units coursing through common lumbar roots in the majority of animals tested, suggesting that ventral root recordings alone are not a reliable means of monitoring phasic hindlimb flexor and extensor activity during locomotion in this preparation. Part II compares the different patterns of hindlimb flexor and extensor discharge induced by each of N-methyl-D,L-aspartate (NMA), serotonin and acetylcholine (ACh). These findings demonstrate that exogenously applied neurochemicals induce a variety of in vitro motor rhythms although some substances preferentially activate specific patterns. Serotonin was the best single agent for inducing a pattern of flexor-extensor activity consistent with locomotion. Part III examines the role of inhibitory amino acid receptor mechanisms in the coordination of left-right and flexor-extensor discharge during neurochemically induced motor rhythms. These findings indicated that $\gamma$-amino-butyric acid (GABA$\sb{\rm A}$) and glycine receptor activation may mediate reciprocal left-right and flexor-extensor phase relationships during locomotion, and that blockade of these receptors facilitates the expression of rhythms dominated by excitatory coupling within the rhythmogenic network. Part IV investigates the neuroanatomical substrates generating and coordinating motor rhythms induced by different neurochemicals. The results suggest that a serotonin-sensitive oscillatory network capable of generating locomotion is distributed throughout the supralumbar cord whereas NMA- and ACh-activated rhythmogenic elements are distributed throughout the spinal cord. In addition, an extensive propriospinal network of redundantly organized reciprocal excitatory connections exists which may underlie the simultaneous activation of specific combinations of motor groups during locomotion. The findings of this thesis are summarized, some results reported subsequent to publication of Parts I-IV are discussed, and a possible model of the spinal rhythm-generating network is presented.