PMID- 14557544 OWN - NLM STAT- MEDLINE DCOM- 20040105 LR - 20181113 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 100 IP - 22 DP - 2003 Oct 28 TI - Brain-derived neurotrophic factor-dependent unmasking of "silent" synapses in the developing mouse barrel cortex. PG - 13069-74 AB - 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. FAU - Itami, Chiaki AU - Itami C AD - Division of Biochemistry and Cellular Biology, National Institute of Neuroscience, Tokyo 187-8502, Japan. FAU - Kimura, Fumitaka AU - Kimura F FAU - Kohno, Tomoko AU - Kohno T FAU - Matsuoka, Masato AU - Matsuoka M FAU - Ichikawa, Masumi AU - Ichikawa M FAU - Tsumoto, Tadaharu AU - Tsumoto T FAU - Nakamura, Shun AU - Nakamura S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20031013 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Receptors, AMPA) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/deficiency/genetics/pharmacology/*physiology MH - Calcium/physiology MH - Hippocampus/growth & development/*physiology MH - Mice MH - Mice, Knockout MH - Neurons/physiology MH - Receptors, AMPA/drug effects/physiology MH - Somatosensory Cortex/growth & development/*physiology MH - Synapses/*physiology MH - Visual Cortex/growth & development/*physiology PMC - PMC240746 EDAT- 2003/10/15 05:00 MHDA- 2004/01/06 05:00 PMCR- 2004/04/28 CRDT- 2003/10/15 05:00 PHST- 2003/10/15 05:00 [pubmed] PHST- 2004/01/06 05:00 [medline] PHST- 2003/10/15 05:00 [entrez] PHST- 2004/04/28 00:00 [pmc-release] AID - 2131948100 [pii] AID - 10013069 [pii] AID - 10.1073/pnas.2131948100 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13069-74. doi: 10.1073/pnas.2131948100. Epub 2003 Oct 13.