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Cell Rep. 2019 Aug 6;28(6):1410-1418.e4. doi: 10.1016/j.celrep.2019.07.008.

Neocortical High Probability Release Sites Are Formed by Distinct Ca2+ Channel-to-Release Sensor Topographies during Development.

Author information

1
Carl-Ludwig-Institute for Physiology, Medical Faculty, University of Leipzig, Liebigstrasse 27a, 04103 Leipzig, Germany. Electronic address: grit.bornschein@medizin.uni-leipzig.de.
2
Carl-Ludwig-Institute for Physiology, Medical Faculty, University of Leipzig, Liebigstrasse 27a, 04103 Leipzig, Germany.
3
Carl-Ludwig-Institute for Physiology, Medical Faculty, University of Leipzig, Liebigstrasse 27a, 04103 Leipzig, Germany. Electronic address: hartmut.schmidt@medizin.uni-leipzig.de.

Abstract

Coupling distances between Ca2+ channels and release sensors regulate vesicular release probability (pv). Tight coupling is thought to provide a framework for high pv and loose coupling for high plasticity at low pv. At synapses investigated during development, coupling distances decrease, thereby increasing pv and transmission fidelity. We find that neocortical high-fidelity synapses deviate from these rules. Paired recordings from pyramidal neurons with "slow" and "fast" Ca2+ chelators combined with experimentally constrained simulations suggest that coupling tightens significantly during development. However, fluctuation analysis revealed that neither pv (∼0.63) nor the number of release sites (∼8) changes concomitantly. Moreover, the amplitude and time course of presynaptic Ca2+ transients are not different between age groups. These results are explained by high-pv release sites with Ca2+ microdomains in young synapses and nanodomains in mature synapses. Thus, at neocortical synapses, a developmental reorganization of the active zone leaves pv unaffected, emphasizing developmental and functional synaptic diversity.

KEYWORDS:

BAPTA; Ca(2+) channel subtypes; Ca(2+) imaging; EGTA; coupling; microdomain; nanodomain; numerical simulations; pyramidal neurons; quantal parameters

PMID:
31390556
DOI:
10.1016/j.celrep.2019.07.008
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