SILLAR, K.T.; MERRYWEST, S.D.; MCLEAN, D.L.; University of St Andrews: Neuromodulation of developing spinal motor networks

Following their initial assembly, the spinal cord networks controlling rhythmic motor behaviours are subject to neuromodulation by various descending brainstem pathways. These pathways are also involved in the maturation process that occurs in central locomotor networks after birth or hatching. We will review this topic in the model system provided by tadpoles of the amphibian, Xenopus laevis. Hatchling stage 37/38 tadpoles, immobilized in α-bungarotoxin, generate a �fictive� swimming rhythm in which motor neurons fire one spike per cycle. This is superseded by a more flexible larval (stage 42; 1 day later) swimming rhythm in which motor bursts of more variable duration occur. Previously we reported evidence linking the in-growth of serotonergic projections from the raphe to this maturation of swimming. At stage 42, larval swimming is differentially modulated by 5-HT and noradrenaline (NA): 5-HT produces relatively fast, intense swimming; NA leads to slower, weaker swimming. This dual control is largely accomplished via presynaptic regulation of glycine release from commissural interneurons, which couple the two sides of the cord in alternation. More recently we have studied the role of nitric oxide (NO). NO is produced by neurons of the raphe, by presumed noradrenergic neurons of the isthmic region and by descending GABAergic neurons that normally terminate swimming. NO functions as a �metamodulator�, biasing the system towards the noradrenergic form of output, producing short duration, low frequency bouts of swimming. It shortens episodes by facilitating the GABA stopping pathway and it slows swimming by facilitating glycinergic inhibition. NO also depolarizes motor neurons and reduces their input resistance, helping to tune inhibitory synapses.