PMID- 11746350
OWN - NLM
STAT- MEDLINE
DCOM- 20020125
LR  - 20161124
IS  - 0360-4012 (Print)
IS  - 0360-4012 (Linking)
VI  - 66
IP  - 3
DP  - 2001 Nov 1
TI  - Reduced number of functional glutamatergic synapses in hippocampal neurons 
      overexpressing full-length TrkB receptors.
PG  - 327-36
AB  - 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.
CI  - Copyright 2001 Wiley-Liss, Inc.
FAU - Klau, M
AU  - Klau M
AD  - Department of Molecular Neurobiochemistry, Ruhr-University Bochum, Bochum, 
      Germany.
FAU - Hartmann, M
AU  - Hartmann M
FAU - Erdmann, K S
AU  - Erdmann KS
FAU - Heumann, R
AU  - Heumann R
FAU - Lessmann, V
AU  - Lessmann V
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (FM 4-64)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Pyridinium Compounds)
RN  - 0 (Quaternary Ammonium Compounds)
RN  - 0 (Receptors, AMPA)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - P658DCA9XD (neurotrophin 4)
SB  - IM
MH  - Aging/drug effects/physiology
MH  - Animals
MH  - Animals, Newborn
MH  - Brain-Derived Neurotrophic Factor/*metabolism/pharmacology
MH  - Cells, Cultured
MH  - Dendrites/metabolism/ultrastructure
MH  - Down-Regulation/drug effects/*physiology
MH  - Excitatory Postsynaptic Potentials/drug effects/genetics
MH  - Fluorescent Dyes
MH  - Gene Expression Regulation, Developmental/drug effects/physiology
MH  - Glutamic Acid/*metabolism
MH  - Hippocampus/cytology/*growth & development/metabolism
MH  - Nerve Growth Factors/pharmacology
MH  - Neuronal Plasticity/drug effects/physiology
MH  - Neurons/cytology/drug effects/*metabolism
MH  - Presynaptic Terminals/drug effects/metabolism
MH  - Protein Structure, Tertiary/drug effects/genetics
MH  - Pyridinium Compounds
MH  - Quaternary Ammonium Compounds
MH  - Rats
MH  - Receptor, trkB/antagonists & inhibitors/genetics/*metabolism
MH  - Receptors, AMPA/drug effects/metabolism
MH  - Recombinant Fusion Proteins/drug effects/genetics/metabolism
MH  - Synapses/drug effects/*metabolism
MH  - Up-Regulation/drug effects/genetics
EDAT- 2001/12/18 10:00
MHDA- 2002/01/26 10:01
CRDT- 2001/12/18 10:00
PHST- 2001/12/18 10:00 [pubmed]
PHST- 2002/01/26 10:01 [medline]
PHST- 2001/12/18 10:00 [entrez]
AID - 10.1002/jnr.10007 [pii]
AID - 10.1002/jnr.10007 [doi]
PST - ppublish
SO  - J Neurosci Res. 2001 Nov 1;66(3):327-36. doi: 10.1002/jnr.10007.