title: Developmental tightening of cerebellar cortical synaptic influx-release coupling.
abstract: 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.
authors: Carl-Ludwig-Institute for Physiology, 04103 Leipzig, Germany.
authors: David
authors: http://orcid.org/0000-0001-9583-6043
authors: D
authors: Baur
authors: Carl-Ludwig-Institute for Physiology, 04103 Leipzig, Germany.
authors: Grit
authors: http://orcid.org/0000-0002-4871-2686
authors: G
authors: Bornschein
authors: Department of Physiology II, University of Freiburg, D-79104 Freiburg, Germany.
authors: Daniel
authors: http://orcid.org/0000-0002-6078-9811
authors: D
authors: Althof
authors: Department of Anatomy, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan, and.
authors: Masahiko
authors: M
authors: Watanabe
authors: Department of Physiology II, University of Freiburg, D-79104 Freiburg, Germany, BIOSS Centre for Biological Signalling Studies, University of Freiburg, D-79104 Freiburg, Germany.
authors: Akos
authors: A
authors: Kulik
authors: Carl-Ludwig-Institute for Physiology, 04103 Leipzig, Germany.
authors: Jens
authors: http://orcid.org/0000-0003-0497-5625
authors: J
authors: Eilers
authors: Carl-Ludwig-Institute for Physiology, 04103 Leipzig, Germany, hartmut.schmidt@medizin.uni-leipzig.de.
authors: Hartmut
authors: http://orcid.org/0000-0002-9516-423X
authors: H
authors: Schmidt
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000378:metabolism; D065096:Calcium Chelating Agents / Q000494:pharmacology; D020013:Calcium Signaling; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis; D011689:Purkinje Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D013569:Synapses / Q000378:metabolism* / Q000502:physiology
chemical_list: D002118:Calcium; D020864:Calcium Channels, N-Type; D065096:Calcium Chelating Agents
keywords: calcium channels; calcium chelators; coupling; presynaptic calcium; release probability; short-term plasticity
references: Cell Calcium. 1998 Nov-Dec;24(5-6):345-57
references: 10091004
references: Neuron. 1999 Jun;23(2):399-409
references: 10399944
references: Ann N Y Acad Sci. 1999 Apr 30;868:144-59
references: 10414292
references: Trends Neurosci. 2000 Mar;23(3):105-13
references: 10675910
references: Biophys J. 2000 Dec;79(6):3009-18
references: 11106608
references: J Neurosci. 2000 Dec 15;20(24):9162-73
references: 11124994
references: J Physiol. 2001 Mar 15;531(Pt 3):807-26
references: 11251060
references: J Physiol. 2001 Aug 1;534(Pt 3):861-71
references: 11483715
references: J Neurosci. 2001 Sep 1;21(17):6666-72
references: 11517256
references: J Physiol. 2001 Sep 1;535(Pt 2):445-72
references: 11533136
references: J Neurosci. 2002 Feb 1;22(3):728-39
references: 11826102
references: Neuron. 2002 Jan 31;33(3):439-52
references: 11832230
references: J Neurosci. 2002 Mar 1;22(5):1648-67
references: 11880495
references: Eur J Neurosci. 2003 Jun;17(12):2563-72
references: 12823463
references: J Physiol. 1992 May;450:273-301
references: 1331424
references: Science. 1992 Dec 11;258(5089):1812-5
references: 1465619
references: J Neurosci Methods. 2003 Dec 15;130(2):127-41
references: 14667542
references: Neuron. 2003 Dec 18;40(6):1173-83
references: 14687551
references: Eur J Neurosci. 2004 Apr;19(8):2169-78
references: 15090043
references: Nature. 2004 Apr 22;428(6985):856-60
references: 15103377
references: Biophys J. 1977 Apr;18(1):3-22
references: 15667
references: J Neurosci. 2005 Mar 23;25(12):3246-57
references: 15788782
references: J Neurosci. 2005 Apr 20;25(16):4131-40
references: 15843616
references: Nat Neurosci. 2005 Oct;8(10):1319-28
references: 16158066
references: J Neurosci. 2005 Dec 14;25(50):11655-65
references: 16354924
references: J Neurosci Methods. 2006 Jun 15;153(2):250-60
references: 16376992
references: Neuron. 2006 Mar 16;49(6):833-44
references: 16543132
references: J Gen Physiol. 1991 Oct;98(4):751-70
references: 1660061
references: Science. 2006 May 19;312(5776):1051-4
references: 16614170
references: J Neurosci. 2006 Apr 19;26(16):4289-97
references: 16624949
references: J Neurosci. 1991 Jun;11(6):1496-507
references: 1675264
references: Ann N Y Acad Sci. 1991;635:365-81
references: 1683754
references: Neuron. 2007 Feb 15;53(4):563-75
references: 17296557
references: J Neurosci. 2007 Jul 25;27(30):7888-98
references: 17652580
references: Proc Natl Acad Sci U S A. 2007 Nov 6;104(45):17831-6
references: 17965230
references: PLoS Biol. 2007 Nov;5(11):e311
references: 18044987
references: Nature. 2007 Dec 20;450(7173):1245-8
references: 18097412
references: Neuron. 2008 Feb 28;57(4):536-45
references: 18304483
references: Neuron. 2008 Sep 25;59(6):861-72
references: 18817727
references: J Neurosci. 2008 Dec 31;28(53):14450-8
references: 19118179
references: Braz J Med Biol Res. 2009 Jan;42(1):94-104
references: 19219302
references: J Physiol. 2009 May 1;587(Pt 9):1889-96
references: 19273572
references: Nat Neurosci. 2009 Apr;12(4):463-73
references: 19287389
references: J Physiol. 2009 Jun 15;587(Pt 12):3009-23
references: 19403608
references: Neuron. 2009 Oct 29;64(2):227-39
references: 19874790
references: Nat Rev Neurosci. 2010 Jan;11(1):30-43
references: 19997115
references: Neuron. 2010 Jul 15;67(1):100-15
references: 20624595
references: Neuron. 2010 Nov 18;68(4):710-23
references: 21092860
references: Cell. 2011 Jan 21;144(2):282-95
references: 21241895
references: Neuron. 2011 Jan 27;69(2):304-16
references: 21262468
references: J Neurosci. 2011 Apr 6;31(14):5235-43
references: 21471358
references: Nat Rev Neurosci. 2011 Dec 20;13(1):7-21
references: 22183436
references: J Neurosci. 2012 Feb 29;32(9):3267-80
references: 22378898
references: Neuron. 2012 Jul 12;75(1):11-25
references: 22794257
references: J Neurosci. 2012 Dec 12;32(50):18157-76
references: 23238730
references: Curr Biol. 2013 Feb 4;23(3):244-9
references: 23273895
references: J Physiol. 2013 Jul 1;591(13):3167-78
references: 23459757
references: J Physiol. 2013 Jul 1;591(13):3355-70
references: 23671160
references: J Physiol. 2013 Aug 15;591(16):3887-99
references: 23732647
references: Nat Commun. 2013;4:2392
references: 23999086
references: Nat Med. 2013 Oct;19(10):1227-31
references: 24100992
references: Science. 2014 Feb 7;343(6171):665-70
references: 24503854
references: Neuron. 2014 Apr 2;82(1):181-94
references: 24698275
references: J Neurosci. 2014 Oct 29;34(44):14687-96
references: 25355221
references: J Physiol. 1967 Nov;193(2):419-32
references: 6065887
references: Nature. 1981 Apr 9;290(5806):527-8
references: 7219539
references: Neuron. 1995 Sep;15(3):675-88
references: 7546746
references: J Neurosci. 1996 Sep 15;16(18):5661-71
references: 8795622
references: Biophys J. 1997 Feb;72(2 Pt 1):728-53
references: 9017200
references: J Neurosci. 1997 Sep 15;17(18):6961-73
references: 9278532
references: Cell Calcium. 1997 Oct;22(4):255-68
references: 9481476
references: Biophys J. 1998 Mar;74(3):1549-63
references: 9512051
references: Neuron. 1998 Mar;20(3):389-99
references: 9539117
references: J Physiol. 1998 Aug 1;510 ( Pt 3):881-902
references: 9660900
references: J Neurosci. 1998 Oct 15;18(20):8214-27
references: 9763467
references: J Physiol. 1998 Nov 15;513 ( Pt 1):135-48
references: 9782165