Effects of noradrenaline on locomotor rhythm-generating networks in the isolated neonatal rat spinal cord

We have studied the effects of the biogenic amine noradrenaline (NA) on mot or activity in the isolated neonatal rat spinal cord. The motor output was recorded with suction electrodes from the lumbar ventral roots. When applie d on its own, NA (0.5-50 mu M) elicited either no measurable root activity, or activity of a highly variable nature. When present, the NA-induced acti vity consisted of either low levels of unpatterned tonic discharges, or an often irregular, slow rhythm that displayed a high degree of synchrony betw een antagonistic motor pools. Finally, in a few cases, NA induced a slow lo comotor-like rhythm, in which activity alternated between the left and righ t sides, and between rostral and caudal roots on the same side. As shown pr eviously, stable locomotor activity could be induced by bath application of N-methyl-D-aspartate (NMDA; 4-8.5 mu M) and/or serotonin (5-HT; 4-20 mu M) . NA modulated this activity by decreasing the cycle frequency and increasi ng the ventral root burst duration. These effects were dose dependent in th e concentration range 1-5 mu M. In contrast. at no concentration tested did NA have consistent effects on burst amplitudes or on the background activi ty of the ongoing rhythm, Moreover, NA did not obviously affect the left/ri ght and rostrocaudal alternation of the NMDA/5-HT rhythm. The NMDA/5-HT loc omotor rhythm sometimes displayed a time-dependent breakdown in coordinatio n, ultimately resulting in tonic ventral root activity. However, the additi on of NA to the NMDA/5-HT saline could reinstate a well-coordinated locomot or rhythm. We conclude that exogenously applied NA can elicit tonic activit y or can trigger a slow, irregular and often synchronous motor pattern. Whe n NA is applied during ongoing locomotor activity, the amine has a distinct slowing effect on the rhythm while preserving the normal coordination betw een flexors and extensors. The ability of NA to "rescue" rhythmic locomotor activity after its time-dependent deterioration suggests that the amine ma y be important in the maintenance of rhythmic motor activity.