Reduced number of functional glutamatergic synapses in hippocampal neurons overexpressing full-length TrkB receptors
✍ Scribed by Michele Klau; Matthias Hartmann; Kai S. Erdmann; Rolf Heumann; Volkmar Lessmann
- Publisher
- John Wiley and Sons
- Year
- 2001
- Tongue
- English
- Weight
- 291 KB
- Volume
- 66
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
Brain‐derived neurotrophic factor (BDNF) acutely modulates the efficacy of central glutamatergic synapses via activation of the receptor tyrosine kinase TrkB. On a longer time scale, recent evidence suggests an additional role of TrkB signaling in the formation of excitatory synaptic connections. Here, we have overexpressed full‐length TrkB receptors (fl‐TrkB) in hippocampal neurons, to investigate the contribution of BDNF signaling to the maturation of glutamatergic synapses. Using patch clamp recordings, we show a three‐fold reduction in glutamatergic excitatory autaptic and synaptic current amplitudes in neurons overexpressing fl‐TrkB, and application of saturating concentrations of BDNF and NT‐4/5 completely reverses this effect. Compatible with these overexpression data, in untransfected neurons, scavenging of endogenous BDNF and NT‐4/5 by TrkB‐IgGs reduces excitatory autaptic current (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 necessary to observe the EAC reduction. Labeling of presynaptic terminals with FM 4‐64 revealed, that the reduced EAC amplitudes in fl‐TrkB overexpressing neurons are accompanied by a two‐fold reduction in synapse number. These results suggest, that ligand‐independent signaling through fl‐TrkB receptors can decrease glutamatergic synaptic strength, if sufficient amounts of BDNF or NT‐4/5 are not available. J. Neurosci. Res. 66:327–336, 2001. © 2001 Wiley‐Liss, Inc.