Reduced number of functional glutamatergic synapses in hippocampal neuronsoverexpressing full-length TrkB receptors

Brain-derived neurotrophic factor (BDNF) acutely modulates the efficacy of central glutamatergic synapses via activation of the receptor tyrosine kina se TrkB. On a longer time scale, recent evidence suggests an additional rol e of TrkB signaling in the formation of excitatory synaptic connections. He re, we have overexpressed full-length TrkB receptors (fl-TrkB) in hippocamp al neurons, to investigate the contribution of BDNF signaling to the matura tion of glutamatergic synapses. Using patch clamp recordings, we show a thr ee-fold reduction in glutamatergic excitatory autaptic and synaptic current amplitudes in neurons overexpressing fl-TrkB, and application of saturatin g concentrations of BDNF and NT-4/5 completely reverses this effect. Compat ible with these overexpression data, in untransfected neurons, scavenging o f endogenous BDNF and NT-4/5 by TrkB-IgGs reduces excitatory autaptic curre nt (EAC) amplitudes. By overexpression of truncated TrkB receptors (TrkB.T1 , TrkB.T2) and a chimeric receptor containing only the intracellular domain of fl-TrkB, we show that intra- and extracellular domains of fl-TrkB are n ecessary to observe the EAC reduction. Labeling of presynaptic terminals wi th FM 4-64 revealed, that the reduced EAC amplitudes in fl-TrkB overexpress ing neurons are accompanied by a two-fold reduction in synapse number. Thes e results suggest, that ligand-independent signaling through fl-TrkB recept ors can decrease glutamatergic synaptic strength, if sufficient amounts of BDNF or NT-4/5 are not available. (C) 2001 Wiley-Liss, Inc.