PMID- 16709633 OWN - NLM STAT- MEDLINE DCOM- 20060926 LR - 20181113 IS - 0022-3751 (Print) IS - 1469-7793 (Electronic) IS - 0022-3751 (Linking) VI - 574 IP - Pt 3 DP - 2006 Aug 1 TI - BDNF increases release probability and the size of a rapidly recycling vesicle pool within rat hippocampal excitatory synapses. PG - 787-803 AB - 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. FAU - Tyler, William J AU - Tyler WJ AD - Department of Neurobiology, SHEL-1002, University of Alabama at Birmingham, 1825 University Blvd, Birmingham, AL 35294-2182, USA. FAU - Zhang, Xiao-lei AU - Zhang XL FAU - Hartman, Kenichi AU - Hartman K FAU - Winterer, Jochen AU - Winterer J FAU - Muller, Wolfgang AU - Muller W FAU - Stanton, Patric K AU - Stanton PK FAU - Pozzo-Miller, Lucas AU - Pozzo-Miller L LA - eng GR - P30 HD038985/HD/NICHD NIH HHS/United States GR - NS44421/NS/NINDS NIH HHS/United States GR - R01 NS040593/NS/NINDS NIH HHS/United States GR - R56 NS044421/NS/NINDS NIH HHS/United States GR - P30-HD38985/HD/NICHD NIH HHS/United States GR - P01 HD038760/HD/NICHD NIH HHS/United States GR - R01 NS044421/NS/NINDS NIH HHS/United States GR - P01-HD38760/HD/NICHD NIH HHS/United States GR - NS40593/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20060518 PL - England TA - J Physiol JT - The Journal of physiology JID - 0266262 RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Animals MH - Animals, Newborn MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Cells, Cultured MH - Computer Simulation MH - Excitatory Postsynaptic Potentials/drug effects/*physiology MH - Hippocampus/drug effects/*physiology MH - *Models, Neurological MH - Models, Statistical MH - Rats MH - Rats, Sprague-Dawley MH - Synaptic Transmission/drug effects/*physiology MH - Synaptic Vesicles/drug effects/*physiology PMC - PMC1817733 EDAT- 2006/05/20 09:00 MHDA- 2006/09/27 09:00 PMCR- 2007/08/01 CRDT- 2006/05/20 09:00 PHST- 2006/05/20 09:00 [pubmed] PHST- 2006/09/27 09:00 [medline] PHST- 2006/05/20 09:00 [entrez] PHST- 2007/08/01 00:00 [pmc-release] AID - jphysiol.2006.111310 [pii] AID - 10.1113/jphysiol.2006.111310 [doi] PST - ppublish SO - J Physiol. 2006 Aug 1;574(Pt 3):787-803. doi: 10.1113/jphysiol.2006.111310. Epub 2006 May 18.