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The Journal of Neuroscience, September 15, 1999, 19(18):7983-7990
Relative Contribution of Endogenous Neurotrophins in Hippocampal
Long-Term Potentiation
Guiquan
Chen,
Roland
Kolbeck,
Yves-Alain
Barde,
Tobias
Bonhoeffer, and
Albrecht
Kossel
Max-Planck-Institut für Neurobiologie, D-82152
München-Martinsried, Germany
Recent evidence has shown that brain-derived neurotrophic factor
(BDNF) is involved in hippocampal long-term potentiation (LTP). Because
the reagents used in acute experiments react not only with BDNF but
also with neurotrophin-4/5 (NT4/5) and neurotrophin-3 (NT3), we
examined the involvement of these neurotrophins in LTP using two highly
specific, function-blocking monoclonal antibodies against BDNF and NT3,
as well as a TrkB-IgG fusion protein. Our results show that NT3
antibodies did not have any effects on LTP. However, both TrkB-IgG
fusion proteins and BDNF antibody similarly reduced LTP, suggesting
that only BDNF but no other ligands of the TrkB-receptor are likely to
be involved in LTP induction. The reduction in LTP depended on the
inducing stimuli and was only observed with theta-burst stimulation
(TBS) but not with tetanic stimulation. We further observed that LTP
was only reduced if BDNF was blocked before and during TBS stimulation,
and BDNF antibodies did not affect early or late stages of LTP if they were applied 10, 30, or 60 min after TBS stimulation. These results point toward a specific and unique role of endogenous BDNF but not of
other neurotrophins in the process of TBS-induced hippocampal LTP.
Additionally, they suggest that endogenous BDNF is required for a
limited time period only shortly before or around LTP induction but not
during the whole process of LTP.
Key words:
BDNF; NT3; NT4/5; monoclonal antibodies; TrkB-IgG fusion
protein; LTP
Copyright © 1999 Society for Neuroscience 0270-6474/99/19187983-08$05.00/0
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