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The Journal of Neuroscience, June 15, 2001, 21(12):4249-4258
BDNF Enhances Quantal Neurotransmitter Release and Increases the
Number of Docked Vesicles at the Active Zones of Hippocampal Excitatory
Synapses
William J.
Tyler and
Lucas D.
Pozzo-Miller
Department of Neurobiology, University of Alabama at Birmingham,
Birmingham, Alabama 35294-0021
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.
Key words:
active zones; CA1; dendritic spines; docked vesicles; hippocampus; mEPSCs; neurotrophins; synapses; TrkB receptors
Copyright © 2001 Society for Neuroscience 0270-6474/01/21124249-10$05.00/0
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