BDNF enhances quantal neurotransmitter release and increases the number ofdocked vesicles at the active zones of hippocampal excitatory synapses

Brain-derived neurotrophic factor (BDNF) is emerging as a key mediator of a ctivity-dependent modifications of synaptic strength in the CNS. We investi gated the hypothesis that BDNF enhances quantal neurotransmitter release by modulating the distribution of synaptic vesicles within presynaptic termin als using organotypic slice cultures of postnatal rat hippocampus. BDNF spe cifically increased the number of docked vesicles at the active zone of exc itatory synapses on CA1 dendritic spines, with only a small increase in act ive zone size. In agreement with the hypothesis that an increased docked ve sicle density enhances quantal neurotransmitter release, BDNF increased the frequency, but not the amplitude, of AMPA receptor-mediated miniature EPSC s (mEPSCs) recorded from CA1 pyramidal neurons in hippocampal slices. Synap se number, independently estimated from dendritic spine density and electro n microscopy measurements, was also increased after BDNF treatment, indicat ing that the actions of BNDF on mEPSC frequency can be partially attributed to an increased synaptic density. Our results further suggest that all the se actions were mediated via tyrosine kinase B (TrkB) receptor activation, established by inhibition of plasma membrane tyrosine kinases with K-252a. These results provide additional evidence of a fundamental role of the BDNF -TrkB signaling cascade in synaptic transmission, as well as in cellular mo dels of hippocampus-dependent learning and memory.