LOCALIZATION OF THE SPINAL NETWORK ASSOCIATED WITH GENERATION OF HINDLIMB LOCOMOTION IN THE NEONATAL RAT AND ORGANIZATION OF ITS TRANSVERSECOUPLING SYSTEM

The segmental organization of the hindlimb locomotor pattern generator s and the coordination of rhythmic motor activity were studied in isol ated spinal cords of the neonatal rat. All lumbar segments and many th oracic and sacral segments of the cord exhibited an alternating left-r ight rhythm in the presence of serotonin (5-HT) and N-methyl-D-asparta te (NMDA). 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 seg ments. A fast alternating rhythm persisted in rostral lumbar segments after transection of the cord at mid-L(3). A much stower alternating r hythm was found in the detached caudal lumbar segments after elevation of the NMDA concentration. These findings suggest that neurogensis of hindlimb locomotion is not restricted to L(1)/L(2), and that the lumb ar pattern generators exhibit rostrocaudal specialization. An alternat ing left-right rhythm persisted in lumbar cords of midsagittally split preparations that were kept with either L(1), L(2), L(3), Or L(4) as the only bilaterally intact segment. An alternating rhythm persisted a lso in preparations that were midsagittally split up to T-13-T-12, Or down to L(4) Extension of these lesions led to a bilaterally synchrono us rhythm or to left-right independent rhythms in the lumbar cord. The se results indicated that the transverse coupling system in the caudal -thoracic and lumbar segments is specialized and that left-right alter nation in the lumbar cord can be carried out by the cross connectivity , which is relayed at least through the T-12-L(4) segments. Bath appli cation of the glycine receptor antagonist strychnine, or the gamma-ami nobutyric acid-A (GABA(A)) receptor blocker bicuculline, induced in th e presence of NMDA and 5-HT a bilaterally synchronous rhythm in any in tact or detached segment of the cord and in midsagittally split prepar ations with few bilaterally intact upper thoracic or lower sacral segm ents. A strychnine-resistant left-right alternating rhythm was found i n the presence of 5-HT and NMDA in preparations that were treated with the non-NMDA receptor blocker 6-cyano-7-nitroquinoxaline (CNQX) befor e and during the application of strychnine. Subsequent washout of CNQX immediately induced a bilateral synchronous rhythm. These results sug gest that the phase relation between the hemicords during the rhythm i s determined by a dynamic interplay between the excitatory and inhibit ory cross connectivity, and that this interplay can be modulated exper imentally. Local application of strychnine to L(2) kept bilaterally in tact in midsagittally split preparations perturbed but did not complet ely block the alternating pattern of the rhythm induced by 5-HT and NM DA. Local application of bicuculline under the same conditions prolong ed the cycle time and had no effect on left-right alternation. These r esults, together with those described above, suggest that left-right a lternation is mediated mainly by strychnine-sensitive glycine receptor s with possible contribution of strychnine-resistant glycine receptors and/or GABAA receptors.