Localization of the Spinal Network Associated With Generation of Hindlimb Locomotion in the Neonatal Rat and Organization of Its Transverse Coupling System

Abstract

The segmental organization of the hindlimb locomotor pattern generators and the coordination of rhythmic motor activity were studied in isolated spinal cords of the neonatal rat. All lumbar segments and many thoracic and sacral segments of the cord exhibited an alternating left-right rhythm in the presence of serotonin (5-HT) and N-methyl-D-aspartate (NDMA). Other thoracic segments exhibited a synchronized left-right rhythm or an irregular bursting activity. Transection of the cord at the thoracolumbar or lumbosacral junction abolished the rhythmicity of nonlumbar segments and had no affect on the rhythmicity of lumbar segments. A fast alternating rhythm persisted in rostral lumbar segments after transection of the cord at mid-L3. A much slower alternating rhythm was found in the detached caudal lumbar segments after elevation of the NMDA concentration. These findings suggest that neurogenesis of hindlimb locomotion is not restricted to L1/L2, and that the lumbar pattern generators exhibited rostrocaudal specialization. An alternating left-right rhythm persisted in lumbar cords of midsagittally split preparations that were kept with either L1, L2, L3, or L4 as the only bilaterally intact segment. An alternating rhythm persisted also in preparations that were midsagittally split up to T13-T12, or down to L4. Extension of these lesions led to a bilaterally synchronous rhythm or to left-right independent rhythms in the lumbar cord. These results indicated that the transverse coupling system in the caudal-thoracic and lumbar segments in specialized and that left-right alternation in the lumbar cord can be carried out by the cross connectivity, which is relayed at least through the T12-L4 segments. Bath application of the glycine receptor antagonist strychnine, or the gamma-aminobutyric acid-A (GABAA) receptor blocker bicuculline, induced in the presence of NMDA and 5-HT a bilaterally synchronous rhythm in any intact or detached segment of the cord and in midsagittally split preparations with few bilaterally intact upper thoracic or lower sacral segments. A strychnine-resistant left-right alternating rhythm was found in the presence of 5-HT and NMDA in preparations that were treated with the non-NMDA receptor blocker 6-cyano-7-nitroquinoxaline (CNQX) before and during the application of strychnine. Subsequent washout of CNQX immediately induced a bilateral synchronous rhythm. These results suggest that the phase relation between the hemicords during the rhythm is determined by a dynamic interplay between the excitatory and inhibitory cross connectivity, and that this interplay can be modulated experimentally. Local application of strychnine to L2 kept bilaterally intact in midsagittally split preparations perturbed but did not completely block the alternating pattern of the rhythm induced by 5-HT and NMDA. Local application of bicuculline under the same conditions prolonged the cycle time and had no effect on left-right alternation. These results, together with those described above, suggest that left-right alternatio...

Neuronal Substrates for State-Dependent Changes in Coordination between Motoneuron Pools during Fictive Locomotion in the Lamprey Spinal Cord

“…To better assess the significance of the observed correlation coefficient, both the SE (dashed line in all correlations) and the fourfold SE (solid line in all correlations) were calculated and shown in the figures (cf. Kremer and Lev-Tov, 1997;Cangiano and Grillner, 2005).…”

“…Cross-correlations were computed for every section and, from the entire set, an average and SE were obtained. Membrane potential oscillations were considered significantly correlated to ventral root bursting if the central peak of the average cross-correlation exceeded four times the SE (Kremer and Lev-Tov, 1997).…”

Characterization of Sacral Interneurons That Mediate Activation of Locomotor Pattern Generators by Sacrocaudal Afferent Input

“…Spinal cords (T6-Co3) were isolated from P1-P3 isoflurane-anesthetized male or female rats (Lev-Tov and Delvolvé, 2000;Lev-Tov et al, 2000;Delvolvé et al, 2001;Blivis et al, 2007). Preparations were transferred to a recording chamber and superfused continuously with an oxygenated artificial CSF (Kremer and Lev-Tov, 1997;Lev-Tov et al, 2000;Delvolvé et al, 2001;Blivis et al, 2007).…”

Different effect of locomotor exercise on the homogenate concentration of amino acids and monoamines in the rostral and caudal lumbar segments of the spinal cord in the rat

“…10,32 Several other lines of evidence indicate that in the neonatal rat, the network of interconnected spinal interneurons, which are capable of generating locomotor-like activity, located in the rostral lumbar segments shows greater capacity for rhythmicity than that in other segments. 13,14,28 Noteworthy, Gabbay and Lev-Tov 33 showed that in early developmental period not only rostral lumbar but also sacrococcygeal segments responded differently to NA than to caudal lumbar segments. The bath-applied NA induced fast rhythms, which mimicked locomotor activity of the spinal cord in rostro-lumbar and sacrococcygeal, but not in caudal lumbar segments.…”

“…The data indicating that the network of interconnected spinal interneurons located in rostral lumbar segments of the rat may play prominent role in the control of spinally distributed locomotor network [10][11][12][13][14] prompted us to verify whether the neurochemical activity in rostral versus caudal lumbar segments is similarly modulated by long-term, moderate locomotor exercise.…”