Relative Contribution of Endogenous Neurotrophins in Hippocampal Long-Term Potentiation

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Abstract
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.