title: Ca2+ channel to synaptic vesicle distance accounts for the readily releasable pool kinetics at a functionally mature auditory synapse.
abstract: Precise regulation of synaptic vesicle (SV) release at the calyx of Held is critical for auditory processing. At the prehearing calyx of Held, synchronous and asynchronous release is mediated by fast and slow releasing SVs within the readily releasable pool (RRP). However, the posthearing calyx has dramatically different release properties. Whether developmental alterations in RRP properties contribute to the accelerated release time course found in posthearing calyces is not known. To study these questions, we performed paired patch-clamp recordings, deconvolution analysis, and numerical simulations of buffered Ca(2+) diffusion and SV release in postnatal day (P) 16-19 mouse calyces, as their release properties resemble mature calyces of Held. We found the P16-P19 calyx RRP consists of two pools: a fast pool (τ ≤ 0.9 ms) and slow pool (τ ∼4 ms), in which release kinetics and relative composition of the two pools were unaffected by 5 mm EGTA. Simulations of SV release from the RRP revealed that two populations of SVs were necessary to reproduce the experimental release rates: (1) SVs located close (∼5-25 nm) and (2) more distal (25-100 nm) to VGCC clusters. This positional coupling was confirmed by experiments showing 20 mm EGTA preferentially blocked distally coupled SVs. Lowering external [Ca(2+)] to in vivo levels reduced only the fraction SVs released from the fast pool. Therefore, we conclude that a dominant parameter regulating the mature calyx RRP release kinetics is the distance between SVs and VGCC clusters.
authors: Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute, Jupiter, Florida 33458.
authors: Zuxin
authors: Z
authors: Chen
authors: Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute, Jupiter, Florida 33458, Integrative Program in Biology and Neuroscience, Florida Atlantic University, Jupiter, Florida 33458.
authors: Brati
authors: B
authors: Das
authors: Laboratory of Dynamic Neuronal Imaging, Institut Pasteur, 75724 Paris Cedex 15, France, and CNRS UMR 3571, 75724 Paris Cedex 15, France.
authors: Yukihiro
authors: http://orcid.org/0000-0002-8820-7780
authors: Y
authors: Nakamura
authors: Laboratory of Dynamic Neuronal Imaging, Institut Pasteur, 75724 Paris Cedex 15, France, and CNRS UMR 3571, 75724 Paris Cedex 15, France.
authors: David A
authors: DA
authors: DiGregorio
authors: Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute, Jupiter, Florida 33458, sam.young@mpfi.org.
authors: Samuel M
authors: SM
authors: Young
mesh_terms: D000818:Animals; D001306:Auditory Pathways / Q000378:metabolism / Q000502:physiology; D001933:Brain Stem / Q000378:metabolism* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials; D005089:Exocytosis; D051379:Mice; D008810:Mice, Inbred C57BL; D013569:Synapses / Q000378:metabolism* / Q000502:physiology; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000502:physiology
chemical_list: D015220:Calcium Channels; D002118:Calcium
keywords: active zone; calcium channels; calyx of Held; priming; readily releasable pool; synaptic vesicle
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