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Updated: Apr 19, 2026
Vibrodissociation of Neurons from Rodent Brain Slices to Study Synaptic Transmission and Image Presynaptic Terminals
Published on: May 25, 2011
Nanoscale distribution of presynaptic Ca(2+) channels and its impact on vesicular release during development
Yukihiro Nakamura1, Harumi Harada2, Naomi Kamasawa3
1Laboratory of Molecular Synaptic Function, Graduate School of Brain Science, Doshisha University, Kyoto 610-0394, Japan; Cellular & Molecular Synaptic Function Unit, Okinawa Institute of Science and Technology (OIST) Graduate University, Okinawa 904-0495, Japan; Laboratory of Dynamic Neuronal Imaging, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France; CNRS UMR 3571, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
Abstract:
Synaptic efficacy and precision are influenced by the coupling of voltage-gated Ca(2+) 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 immunogold labeling of Cav2.1 channels, local [Ca(2+)] 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 Ca(2+) buffer properties remained constant. Experimentally constrained reaction-diffusion simulations suggest that Ca(2+) 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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