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The Journal of Neuroscience, June 15, 1999, 19(12):4972-4983
Impairments in High-Frequency Transmission, Synaptic Vesicle
Docking, and Synaptic Protein Distribution in the Hippocampus of BDNF
Knockout Mice
Lucas D.
Pozzo-Miller1,
Wolfram
Gottschalk2,
Li
Zhang3,
Kathryn
McDermott1,
Jing
Du2,
Raj
Gopalakrishnan2,
Chikara
Oho2,
Zu-Hang
Sheng3, and
Bai
Lu2
1 Laboratory of Neurobiology, National Institute of
Neurological Diseases and Stroke (NINDS), 2 Unit on Synapse
Development and Plasticity, Laboratory of Developmental Neurobiology,
National Institute of Child Health and Human Development,
3 Unit on Synaptic Function, NINDS, National Institutes of
Health, Bethesda, Maryland 20892
Brain-derived neurotrophic factor (BDNF) promotes long-term
potentiation (LTP) at hippocampal CA1 synapses by a presynaptic enhancement of synaptic transmission during high-frequency stimulation (HFS). Here we have investigated the mechanisms of BDNF action using
two lines of BDNF knockout mice. Among other presynaptic impairments,
the mutant mice exhibited more pronounced synaptic fatigue at CA1
synapses during high-frequency stimulation, compared with wild-type
animals. Quantitative analysis of CA1 synapses revealed a significant
reduction in the number of vesicles docked at presynaptic active zones
in the mutant mice. Synaptosomes prepared from the mutant hippocampus
exhibited a marked decrease in the levels of synaptophysin as well as
synaptobrevin [vesicle-associated membrane protein (VAMP-2)], a
protein known to be involved in vesicle docking and fusion. Treatment
of the mutant slices with BDNF reversed the electrophysiological and
biochemical deficits in the hippocampal synapses. Taken together, these
results suggest a novel role for BDNF in the mobilization and/or
docking of synaptic vesicles to presynaptic active zones.
Key words:
BDNF; knockout mice; hippocampus; synaptic fatigue; vesicle docking; synaptobrevin; synaptophysin
Copyright © 1999 Society for Neuroscience 0270-6474/99/19124972-12$05.00/0
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[Abstract]
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B. Xu, W. Gottschalk, A. Chow, R. I. Wilson, E. Schnell, K. Zang, D. Wang, R. A. Nicoll, B. Lu, and L. F. Reichardt
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[Abstract]
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N. Taniguchi, N. Takada, F. Kimura, and T. Tsumoto
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V. F. Rafuse, L. Polo-Parada, and L. T. Landmesser
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[Abstract]
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D. D. Murphy, S. M. Rueter, J. Q. Trojanowski, and V. M.-Y. Lee
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J. D. Sweatt
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B. Berninger, A. F. Schinder, and M.-m. Poo
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[Abstract]
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