PMID- 11404410 OWN - NLM STAT- MEDLINE DCOM- 20010712 LR - 20181113 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 21 IP - 12 DP - 2001 Jun 15 TI - BDNF enhances quantal neurotransmitter release and increases the number of docked vesicles at the active zones of hippocampal excitatory synapses. PG - 4249-58 AB - Brain-derived neurotrophic factor (BDNF) is emerging as a key mediator of activity-dependent modifications of synaptic strength in the CNS. We investigated the hypothesis that BDNF enhances quantal neurotransmitter release by modulating the distribution of synaptic vesicles within presynaptic terminals using organotypic slice cultures of postnatal rat hippocampus. BDNF specifically increased the number of docked vesicles at the active zone of excitatory synapses on CA1 dendritic spines, with only a small increase in active zone size. In agreement with the hypothesis that an increased docked vesicle density enhances quantal neurotransmitter release, BDNF increased the frequency, but not the amplitude, of AMPA receptor-mediated miniature EPSCs (mEPSCs) recorded from CA1 pyramidal neurons in hippocampal slices. Synapse number, independently estimated from dendritic spine density and electron microscopy measurements, was also increased after BDNF treatment, indicating that the actions of BNDF on mEPSC frequency can be partially attributed to an increased synaptic density. Our results further suggest that all these 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 models of hippocampus-dependent learning and memory. FAU - Tyler, W J AU - Tyler WJ AD - Department of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0021, USA. FAU - Pozzo-Miller, L D AU - Pozzo-Miller LD LA - eng GR - R01-NS40593-01/NS/NINDS NIH HHS/United States GR - R01 NS040593/NS/NINDS NIH HHS/United States GR - P01 HD038760/HD/NICHD NIH HHS/United States GR - P01-HD38760/HD/NICHD NIH HHS/United States GR - R01 NS040593-09/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Enzyme Inhibitors) RN - 0 (Neurotransmitter Agents) RN - 0 (Receptors, AMPA) RN - 77521-29-0 (alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism/pharmacology MH - Dendrites/metabolism/ultrastructure MH - Enzyme Inhibitors/pharmacology MH - Excitatory Postsynaptic Potentials/drug effects MH - Hippocampus/cytology/*metabolism MH - In Vitro Techniques MH - Neurotransmitter Agents/*metabolism MH - Presynaptic Terminals/*metabolism MH - Pyramidal Cells/drug effects/metabolism/ultrastructure MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, trkB/antagonists & inhibitors/metabolism MH - Receptors, AMPA/metabolism MH - Signal Transduction/drug effects/physiology MH - Synapses/drug effects/*metabolism/ultrastructure MH - Synaptic Vesicles/*metabolism/ultrastructure MH - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/metabolism/pharmacology PMC - PMC2806848 MID - NIHMS166551 EDAT- 2001/06/19 10:00 MHDA- 2001/07/13 10:01 PMCR- 2001/12/15 CRDT- 2001/06/19 10:00 PHST- 2001/06/19 10:00 [pubmed] PHST- 2001/07/13 10:01 [medline] PHST- 2001/06/19 10:00 [entrez] PHST- 2001/12/15 00:00 [pmc-release] AID - 21/12/4249 [pii] AID - 5297 [pii] AID - 10.1523/JNEUROSCI.21-12-04249.2001 [doi] PST - ppublish SO - J Neurosci. 2001 Jun 15;21(12):4249-58. doi: 10.1523/JNEUROSCI.21-12-04249.2001.