BDNF enhances quantal neurotransmitter release and increases the number of docked vesicles at the active zones of hippocampal excitatory synapses.
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.
Tyler
W J
WJ
Department of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0021, USA.
Pozzo-Miller
L D
LD
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D066298:In Vitro Techniques; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000037:antagonists & inhibitors / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism / Q000494:pharmacology
D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D018377:Neurotransmitter Agents; D018091:Receptors, AMPA; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D020813:Receptor, trkB