期刊
NEURON
卷 85, 期 1, 页码 145-158出版社
CELL PRESS
DOI: 10.1016/j.neuron.2014.11.019
关键词
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资金
- Core Research for Evolutional Science and Technology (CREST) of Japan Science and Technology Agency
- Okinawa Institute of Science and Technology (OIST)
- JSPS Core-to-Core Program, A. Advanced Networks
- Japanese Ministry of Education, Culture, Sports, Science and Technology [23700474]
- Centre National de la Recherche Scientifique through Actions Thematiques et Initatives sur Programme
- Fondation Fyssen
- Fondation pour la Recherche Medicale
- Federation pour la Recherche sur le Cerveau
- Agence Nationale de la Recherche [ANR-2007-Neuro-008-01, ANR-2010-BLAN-1411-01]
- European Commission Coordination Action ENINET [LSHM-CT-2005-19063]
- Wellcome Trust [064413, 095667]
- ERC [294667]
- Grants-in-Aid for Scientific Research [221S0003, 25115729, 26117501, 25702054, 23700474] Funding Source: KAKEN
- European Research Council (ERC) [294667] Funding Source: European Research Council (ERC)
Synaptic efficacy and precision are influenced by the coupling of voltage-gated Ca2+ channels (VGCCs) to vesicles. But because the topography of VGCCs and their proximity to vesicles is unknown, a quantitative understanding of the determinants of vesicular release at nanometer scale is lacking. To investigate this, we combined freeze-fracture replica immuno-gold labeling of Ca(v)2.1 channels, local [Ca2+] imaging, and patch pipette perfusion of EGTA at the calyx of Held. Between postnatal day 7 and 21, VGCCs formed variable sized clusters and vesicular release became less sensitive to EGTA, whereas fixed Ca2+ buffer properties remained constant. Experimentally constrained reaction-diffusion simulations suggest that Ca2+ sensors for vesicular release are located at the perimeter of VGCC clusters (<30 nm) and predict that VGCC number per cluster determines vesicular release probability without altering release time course. This perimeter release model provides a unifying framework accounting for developmental changes in both synaptic efficacy and time course.
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