| After a spinal cord injury at thoracic level, locomotion of the hindlimbs can no longer be expressed voluntarily. However it has been demonstrated that an autonomous spinal network in the lumbosacral cord, below the level of injury, is capable of generating a bilateral and alternating hindlimb locomotor pattern, without contribution of supraspinal pathways. To activate this network, different therapeutic approaches are used and in this thesis, we examined intraspinal microstimulation (ISMS) of the lumbar segments, as a novel tool to induce bilateral locomotion in chronically spinalized cats.; To determine the optimal sites in the spinal cord that would induce locomotion. ISMS was applied with a single electrode at different lateralities and depths in segments L3 to L7 in one-week untrained spinal cats (T13) and in three to five-week spinal cats that had recovered locomotion on the treadmill. The stimulation was used with and without clonidine, a noradrenergic alpha2 agonist. Non-locomotor ipsilateral and bilateral responses, as well as locomotor responses were evoked. For each response, the distribution of effective spinal sites followed gradients in the rostrocaudal, mediolateral and dorsoventral axis. Two main types of locomotor responses were observed when clonidine was injected: contralateral hindlimb locomotion, which was mainly evoked medially, and bilateral locomotion, which was only evoked dorsally. In the trained spinal cat, distribution of non-locomotor responses varied somewhat from the untrained cat, but distribution of locomotor responses remained the same.; In combination with clonidine, tonic stimulation at low frequencies (2 to 6 Hz) and low intensity (20-90 muA) was efficient to induce locomotion. Stimulation with trains of pulses were also efficient between 0.65 and 1 train/s. ISMS in trained animals induced a more regular locomotor pattern than in untrained animals. Furthermore, the locomotor pattern varied according to the spinal segment stimulated, exhibiting a larger forward flexion during swing when rostral segments were stimulated and a longer extension during stance when caudal segments were stimulated.; To determine how ISMS could evoke locomotion, stimulation, inactivation or lesioning of different spinal structures were performed. Dorsal root stimulation could evoke a similar bilateral locomotion as is seen with ISMS, which suggests that afferent pathways are probably involved in the production of locomotion by ISMS. Microinjections of yohimbine, a noradrenergic antagonist, in L3 and L4 segments, or a complete second spinal lesion at L3 or L4 abolished all locomotor activity evoked by ISMS at more caudal segments. Progressive dorsoventral lesions at L3 or L4 or restricted ventral lesions at L4 suggest that the integrity of the ventral or ventrolateral funiculi and the integrity of segments L3-L4 are critical for the induction of locomotion by ISMS and by dorsal root stimulation.; Thus, a combination of locomotor training, pharmacology and electrical stimulation might be beneficial to enhance the spinal capacity of generating locomotion after spinal cord injury.; Keywords. spinal cat, intraspinal microstimulation, lumbar spinal cord, motor responses, locomotion, clonidine, locomotor training, dorsal root stimulation, entrainment, yohimbine, spinal lesion... |
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