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 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 alpha-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.
Itami
Chiaki
C
Division of Biochemistry and Cellular Biology, National Institute of Neuroscience, Tokyo 187-8502, Japan.
Kimura
Fumitaka
F
Kohno
Tomoko
T
Matsuoka
Masato
M
Ichikawa
Masumi
M
Tsumoto
Tadaharu
T
Nakamura
Shun
S
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D006624:Hippocampus / Q000254:growth & development / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology; D018091:Receptors, AMPA / Q000187:drug effects / Q000502:physiology; D013003:Somatosensory Cortex / Q000254:growth & development / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D014793:Visual Cortex / Q000254:growth & development / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D018091:Receptors, AMPA; D002118:Calcium