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J Neurosci. 2015 Feb 4;35(5):1858-71. doi: 10.1523/JNEUROSCI.2900-14.2015.

Developmental tightening of cerebellar cortical synaptic influx-release coupling.

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Carl-Ludwig-Institute for Physiology, 04103 Leipzig, Germany.
Department of Physiology II, University of Freiburg, D-79104 Freiburg, Germany.
Department of Anatomy, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan, and.
Department of Physiology II, University of Freiburg, D-79104 Freiburg, Germany, BIOSS Centre for Biological Signalling Studies, University of Freiburg, D-79104 Freiburg, Germany.
Carl-Ludwig-Institute for Physiology, 04103 Leipzig, Germany,


Tight coupling between Ca(2+) channels and the sensor for vesicular transmitter release at the presynaptic active zone (AZ) is crucial for high-fidelity synaptic transmission. It has been hypothesized that a switch from a loosely coupled to a tightly coupled transmission mode is a common step in the maturation of CNS synapses. However, this hypothesis has never been tested at cortical synapses. We addressed this hypothesis at a representative small cortical synapse: the synapse connecting mouse cerebellar cortical parallel fibers to Purkinje neurons. We found that the slow Ca(2+) chelator EGTA affected release significantly stronger at immature than at mature synapses, while the fast chelator BAPTA was similarly effective in both groups. Analysis of paired-pulse ratios and quantification of release probability (pr) with multiple-probability fluctuation analysis revealed increased facilitation at immature synapses accompanied by reduced pr. Cav2.1 Ca(2+) channel immunoreactivity, assessed by quantitative high-resolution immuno-electron microscopy, was scattered over immature boutons but confined to putative AZs at mature boutons. Presynaptic Ca(2+) signals were quantified with two-photon microscopy and found to be similar between maturation stages. Models adjusted to fit EGTA dose-response curves as well as differential effects of the Ca(2+) channel blocker Cd(2+) indicate looser and less homogenous coupling at immature terminals compared with mature ones. These results demonstrate functionally relevant developmental tightening of influx-release coupling at a single AZ cortical synapse and corroborate developmental tightening of coupling as a prevalent phenomenon in the mammalian brain.


calcium channels; calcium chelators; coupling; presynaptic calcium; release probability; short-term plasticity

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