BDNF increases release probability and the size of a rapidly recycling vesicle pool within rat hippocampal excitatory synapses

Abstract

Exerting its actions pre‐, post‐ and peri‐synaptically, brain‐derived neurotrophic factor (BDNF) is one of the most potent modulators of hippocampal synaptic function. Here, we examined the effects of BDNF on a rapidly recycling pool (RRP) of vesicles within excitatory synapses. First, we estimated vesicular release in hippocampal cultures by performing FM4‐64 imaging in terminals impinging on enhanced green fluorescent protein (eGFP)‐labelled dendritic spines – a hallmark of excitatory synapses. Consistent with a modulation of the RRP, BDNF increased the evoked destaining rate of FM4‐64 only during the initial phase of field stimulation. Multiphoton microscopy in acute hippocampal slices confirmed these observations by selectively imaging the RRP, which was loaded with FM1‐43 by hyperosmotic shock. Slices exposed to BDNF showed an increase in the evoked and spontaneous rates of FM1‐43 destaining from terminals in CA1 stratum radiatum, mostly representing excitatory terminals of Schaffer collaterals. Variance‐mean analysis of evoked EPSCs in CA1 pyramidal neurons further confirmed that release probability is increased in BDNF‐treated slices, without changes in the number of independent release sites or average postsynaptic quantal amplitude. Because BDNF was absent during dye loading, imaging, destaining and whole‐cell recordings, these results demonstrate that BDNF induces a long‐lasting enhancement in the probability of transmitter release at hippocampal excitatory synapses by modulating the RRP. Since the endogenous BDNF scavenger TrkB‐IgG prevented the enhancement of FM1‐43 destaining rate caused by induction of long‐term potentiation in acute hippocampal slices, the modulation of a rapidly recycling vesicle pool may underlie the role of BDNF in hippocampal long‐term synaptic plasticity.