title: 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.
authors.affiliation: Department of Neurobiology, SHEL-1002, University of Alabama at Birmingham, 1825 University Blvd, Birmingham, AL 35294-2182, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Tyler
authors.forename: Xiao-lei
authors.initials: XL
authors.lastname: Zhang
authors.forename: Kenichi
authors.initials: K
authors.lastname: Hartman
authors.forename: Jochen
authors.initials: J
authors.lastname: Winterer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Muller
authors.forename: Patric K
authors.initials: PK
authors.lastname: Stanton
authors.forename: Lucas
authors.initials: L
authors.lastname: Pozzo-Miller
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002478:Cells, Cultured; D003198:Computer Simulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008959:Models, Neurological; D015233:Models, Statistical; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor