Effects of BDNF and NT-3 on development of Ia/motoneuron functional connectivity in neonatal rats.

Effects of BDNF and NT-3 on development of Ia/motoneuron functional connectivity in neonatal rats. The effects of neurotrophin administration and neurotrophin removal via administration of tyrosine kinase (trk) immunoadhesins (trk receptor extracellular domains fused with IgG heavy chain) on the development of segmental reflexes were studied in neonatal rats. Brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), trkB-IgG, and trkC-IgG were delivered via subcutaneous injection on days 0, 2, 4, and 6 of postnatal life. Electrophysiological analysis of EPSPs recorded intracellularly in L5 motoneurons in response to stimulation of dorsal root L5 was carried out on postnatal day 8 in the in vitro hemisected spinal cord. Treatment with BDNF resulted in smaller monosynaptic EPSPs with longer latency than those in controls. EPSP amplitude became significantly larger when BDNF was sequestered with trkB-IgG, suggesting that BDNF has a tonic action on the development of this synapse in neonates. Treatment with NT-3 resulted in larger EPSPs, but the decrease noted after administration of trkC-IgG was not significant. Neurotrophins had little effect on the response to high-frequency dorsal root stimulation or on motoneuron properties. Polysynaptic components were exaggerated in BDNF-treated rats and reduced after NT-3 compared with controls. As in control neonates the largest monosynaptic EPSPs in NT-3 and trkB-IgG-treated preparations were observed in motoneurons with relatively large values of rheobase, probably those that are growing the most rapidly. We conclude that supplementary NT-3 and BDNF administered to neonates can influence developing Ia/motoneuron synapses in the spinal cord but with opposite net effects.