Monoaminergic Establishment of Rostrocaudal Gradients of Rhythmicity in the Neonatal Mouse Spinal Cord

Abstract

Bath application of monoamines is a potent method for evoking locomotor activity in neonatal rats and mice. Monoamines also promote functional recovery in adult animals with spinal cord injuries by activating spinal cord networks. However, the mechanisms of their actions on spinal networks are largely unknown. In this study, we tested the hypothesis that monoamines establish rostrocaudal gradients of rhythmicity in the thoracolumbar spinal cord. Isolated neonatal mouse spinal cord preparations (P0-P2) were used. To assay excitability of networks by monoamines, we evoked a disinhibited rhythm by bath application of picrotoxin and strychnine and recorded neurograms from several thoracolumbar ventral roots. We first established that rostral and caudal segments of the thoracolumbar spinal cord had equal excitability by completely transecting preparations at the L3 segmental level and recording the frequency of the disinhibited rhythm from both segments. Next we established that a majority of ventral interneurons retrogradely labeled by calcium green dextran were active during network activity. We then bath applied combinations of monoaminergic agonists [5-HT and dopamine (DA)] known to elicit locomotor activity. Our results show that monoamines establish rostrocaudal gradients of rhythmicity in the thoracolumbar spinal cord. This may be one mechanism by which combinations of monoaminergic compounds normally stably activate locomotor networks.