Brain-Derived Neurotrophic Factor-Dependent Unmasking of "Silent" Synapses in the Developing Mouse Barrel Cortex

Brain-derived neurotrophic factor (BDNF) is a critical modulator of central synaptic functions such as long-term potentiation in the hippocampal and visual cortex. Little is known, however, about its role in the development of excitatory glutamatergic synapses in vivo. We investigated the developmen...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2003-10, Vol.100 (22), p.13069-13074
Main Authors: Itami, Chiaki, Kimura, Fumitaka, Kohno, Tomoko, Matsuoka, Masato, Ichikawa, Masumi, Tsumoto, Tadaharu, Nakamura, Shun
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
Brain
Brain-Derived Neurotrophic Factor - deficiency
Brain-Derived Neurotrophic Factor - genetics
Brain-Derived Neurotrophic Factor - pharmacology
Brain-Derived Neurotrophic Factor - physiology
Calcium - physiology
Critical periods
Genotypes
Hippocampus - growth & development
Hippocampus - physiology
Knockout mice
Mice
Mice, Knockout
Neurology
Neurons
Neurons - physiology
Neuroscience
PDZ protein
PDZ proteins
Receptors
Receptors, AMPA - drug effects
Receptors, AMPA - physiology
Research grants
Somatosensory Cortex - growth & development
Somatosensory Cortex - physiology
Synapses
Synapses - physiology
Synaptic transmission
TrkB protein
Visual Cortex - growth & development
Visual Cortex - physiology
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Summary:Brain-derived neurotrophic factor (BDNF) is a critical modulator of central synaptic functions such as long-term potentiation in the hippocampal and visual cortex. Little is known, however, about its role in the development of excitatory glutamatergic synapses in vivo. We investigated the development of N-methyl-D-aspartate (NMDA) receptor (NMDAR)-only synapses (silent synapses) and found that silent synapses were prominent in acute thalamocortical brain slices from BDNF knockout mice even after the critical period. These synapses could be partially converted to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-containing ones by adding back BDNF alone to the slice or fully converted to together with electric stimulation without affecting NMDAR transmission. Electric stimulation alone was ineffective under the BDNF knockout background. Postsynaptically applied TrkB kinase inhibitor or calcium-chelating reagent blocked this conversion. Furthermore, the AMPAR C-terminal peptides essential for interaction with PDZ proteins postsynaptically prevented the unmasking of silent synapses. These results suggest that endogenous BDNF and neuronal activity synergistically activate AMPAR trafficking into synaptic sites.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2131948100