Spike-timing-dependent BDNF secretion and synaptic plasticity.

In acute hippocampal slices, we found that the presence of extracellular brain-derived neurotrophic factor (BDNF) is essential for the induction of spike-timing-dependent long-term potentiation (tLTP). To determine whether BDNF could be secreted from postsynaptic dendrites in a spike-timing-dependent manner, we used a reduced system of dissociated hippocampal neurons in culture. Repetitive pairing of iontophoretically applied glutamate pulses at the dendrite with neuronal spikes could induce persistent alterations of glutamate-induced responses at the same dendritic site in a manner that mimics spike-timing-dependent plasticity (STDP)-the glutamate-induced responses were potentiated and depressed when the glutamate pulses were applied 20 ms before and after neuronal spiking, respectively. By monitoring changes in the green fluorescent protein (GFP) fluorescence at the dendrite of hippocampal neurons expressing GFP-tagged BDNF, we found that pairing of iontophoretic glutamate pulses with neuronal spiking resulted in BDNF secretion from the dendrite at the iontophoretic site only when the glutamate pulses were applied within a time window of approximately 40 ms prior to neuronal spiking, consistent with the timing requirement of synaptic potentiation via STDP. Thus, BDNF is required for tLTP and BDNF secretion could be triggered in a spike-timing-dependent manner from the postsynaptic dendrite.