Synaptic reliability and temporal precision are achieved via high quantal content and effective replenishment: auditory brainstem versus hippocampus.
Auditory brainstem neurons involved in sound source localization are equipped with several morphological and molecular features that enable them to compute interaural level and time differences. As sound source localization works continually, synaptic transmission between these neurons should be reliable and temporally precise, even during sustained periods of high-frequency activity. Using patch-clamp recordings in acute brain slices, we compared synaptic reliability and temporal precision in the seconds-minute range between auditory and two types of hippocampal synapses; the latter are less confronted with temporally precise high-frequency transmission than the auditory ones. We found striking differences in synaptic properties (e.g. continually high quantal content) that allow auditory synapses to reliably release vesicles at much higher rate than their hippocampal counterparts. Thus, they are indefatigable and also in a position to transfer information with exquisite temporal precision and their performance appears to be supported by very efficient replenishment mechanisms.



At early stations of the auditory pathway, information is encoded by precise signal timing and rate. Auditory synapses must maintain the relative timing of events with submillisecond precision even during sustained and high-frequency stimulation. In non-auditory brain regions, e.g. telencephalic ones, synapses are activated at considerably lower frequencies. Central to understanding the heterogeneity of synaptic systems is the elucidation of the physical, chemical and biological factors that determine synapse performance. In this study, we used slice recordings from three synapse types in the mouse auditory brainstem and hippocampus. Whereas the auditory brainstem nuclei experience high-frequency activity in vivo, the hippocampal circuits are activated at much lower frequencies. We challenged the synapses with sustained high-frequency stimulation (up to 200 Hz for 60 s) and found significant performance differences. Our results show that auditory brainstem synapses differ considerably from their hippocampal counterparts in several aspects, namely resistance to synaptic fatigue, low failure rate and exquisite temporal precision. Their high-fidelity performance supports the functional demands and appears to be due to the large size of the readily releasable pool and a high release probability, which together result in a high quantal content. In conjunction with very efficient vesicle replenishment mechanisms, these properties provide extremely rapid and temporally precise signalling required for neuronal communication at early stations of the auditory system, even during sustained activation in the minute range.
Animal Physiology Group, Department of Biology, University of Kaiserslautern, D-67663, Kaiserslautern, Germany.
Elisa G
EG
Krächan
Animal Physiology Group, Department of Biology, University of Kaiserslautern, D-67663, Kaiserslautern, Germany.
Alexander U
0000-0002-2810-2880
AU
Fischer
Chair for Applied Mathematical Statistics, Department of Mathematics, University of Kaiserslautern, D-67663, Kaiserslautern, Germany.
Jürgen
J
Franke
Animal Physiology Group, Department of Biology, University of Kaiserslautern, D-67663, Kaiserslautern, Germany.
Eckhard
E
Friauf
D000818:Animals; D001306:Auditory Pathways / Q000502:physiology; D001933:Brain Stem / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D009474:Neurons; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission
fidelity of synaptic transmission; sound localization circuits; temporal precision
J Physiol. 2003 Oct 15;552(Pt 2):459-70
14561829
J Neurophysiol. 2004 Aug;92(2):780-9
15277596
PLoS Biol. 2006 Jul;4(7):e207
16774451
Brain Res. 1998 Jul 20;799(2):235-42
9675296
Front Neural Circuits. 2014 Mar 10;8:14
24653676
J Neurophysiol. 2007 Dec;98(6):3349-59
17942618
Neuron. 2014 Oct 22;84(2):416-31
25374362
J Neurophysiol. 1997 Nov;78(5):2438-54
9356395
J Neurosci. 2010 Mar 24;30(12):4210-20
20335456
Cell Tissue Res. 2015 Jul;361(1):177-213
25896885
Hippocampus. 2006;16(1):66-79
16261553
Neuron. 1996 Dec;17(6):1241-9
8982170
Neuron. 2008 Sep 25;59(6):861-72
18817727
Proc Natl Acad Sci U S A. 2016 Jan 19;113(3):E378-86
26715759
Hear Res. 1982 Apr;6(3):241-6
6979535
J Neurophysiol. 2001 Jun;85(6):2324-34
11387379
Cell. 1996 Dec 27;87(7):1339-49
8980239
Neuron. 1997 Jun;18(6):995-1008
9208866
Hippocampus. 2003;13(8):953-61
14750657
Nature. 1994 Oct 6;371(6497):513-5
7935764
J Neurosci. 2008 May 21;28(21):5594-601
18495893
J Cereb Blood Flow Metab. 2001 Oct;21(10):1133-45
11598490
Brain Res. 1989 Aug 7;494(1):187-92
2765919
Nat Neurosci. 2002 Feb;5(2):147-54
11802170
Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):846-9
7846064
Brain Res Dev Brain Res. 1992 Jun 19;67(2):317-26
1511522
J Neurosci. 2000 Feb 15;20(4):1374-85
10662828
J Neurophysiol. 2009 Jul;102(1):349-59
19439675
J Comp Neurol. 1985 Feb 8;232(2):261-85
3973093
J Neurosci. 2012 Oct 17;32(42):14602-16
23077046
Nat Rev Neurosci. 2004 Apr;5(4):304-16
15034555
J Neurosci. 2009 Jul 29;29(30):9510-20
19641114
J Physiol. 2011 Sep 1;589(17):4301-20
21746778
J Neurophysiol. 1999 Jun;81(6):3096-9
10368425
J Physiol. 1992 Dec;458:261-87
1338788
J Neurophysiol. 2008 May;99(5):2510-21
18367696
J Neurosci. 2011 May 4;31(18):6699-709
21543599
Nat Neurosci. 2003 Mar;6(3):282-90
12577063
Neuron. 2002 Dec 19;36(6):1127-43
12495627
J Cereb Blood Flow Metab. 1981;1(1):7-36
7035471
Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):4107-12
10097171
J Neurophysiol. 2006 Jan;95(1):26-32
16162827
J Neurophysiol. 2004 Apr;91(4):1500-9
14645384
Science. 1997 Jan 10;275(5297):220-4
8985017
Nat Neurosci. 2015 Jul;18(7):1008-16
26005852
J Neurosci. 2000 Aug 1;20(15):5594-607
10908596
Neuron. 2014 Sep 17;83(6):1404-17
25199707
Neuron. 2002 Apr 25;34(3):411-23
11988172
Cell. 2014 Feb 13;156(4):825-35
24529383
J Neurophysiol. 1998 Nov;80(5):2255-67
9819241
J Neurophysiol. 2007 Aug;98(2):807-20
17507501
J Neurophysiol. 1966 Jul;29(4):684-97
5966430
J Physiol. 1965 Jun;178(3):505-29
5827910
Hippocampus. 2006;16(9):755-64
16883558
Nature. 2005 Apr 14;434(7035):889-94
15829963
J Am Audiol Soc. 1976 Mar-Apr;1(5):179-84
956003
Mol Cell Neurosci. 2015 Jan;64:9-23
25131618
J Neurochem. 1977 Jul;29(1):13-26
407330
Neuron. 2001 Jan;29(1):7-10
11182076
Nat Rev Neurosci. 2004 Aug;5(8):630-40
15263893
J Physiol. 1982 Feb;323:117-44
6980272
Front Synaptic Neurosci. 2010 Sep 16;2:144
21423530
Hear Res. 1999 Nov;137(1-2):77-90
10545636
Nature. 2006 Feb 23;439(7079):983-7
16496000
Nat Neurosci. 2010 Feb;13(2):232-8
20081852
J Neurosci. 2013 May 29;33(22):9402-7
23719808
Science. 1998 Jul 17;281(5375):419-24
9665886
Neuron. 2014 May 21;82(4):822-35
24853941
Nat Commun. 2015 Jul 15;6:7728
26173895
Nat Neurosci. 1998 Nov;1(7):587-94
10196566
Brain Res. 1978 Apr 7;144(1):11-8
638755
J Neurosci. 1993 Sep;13(9):3904-15
8103555
Hear Res. 2015 Dec;330(Pt B):213-20
26119177
Hippocampus. 2005;15(5):562-78
15884034
J Neurosci. 2011 Feb 9;31(6):2000-8
21307238
Physiol Rev. 2004 Jan;84(1):69-85
14715911
Nature. 1998 Jul 23;394(6691):384-8
9690475
Neuron. 2015 Sep 23;87(6):1131-1142
26402599
J Comp Neurol. 1999 Jul 12;409(4):664-81
10376746
Neuron. 2004 Mar 25;41(6):943-53
15046726
J Gen Physiol. 2010 Sep;136(3):259-72
20805573
Neuron. 2013 Jul 10;79(1):82-96
23770256
J Neurosci. 2014 Aug 13;34(33):10853-69
25122888
PLoS One. 2011;6(10):e25122
21984900
Neuron. 2010 Sep 9;67(5):797-809
20826311
Neuron. 2007 May 24;54(4):567-81
17521570
J Physiol. 2015 Aug 15;593(16):3417-29
25639777
J Neurosci. 2010 Jun 2;30(22):7587-97
20519533
J Biol Chem. 1995 Oct 20;270(42):25273-80
7559667
PLoS Genet. 2009 May;5(5):e1000480
19424431
Hippocampus. 2006;16(9):716-29
16897724
Neuroscience. 2011 Sep 29;192:219-30
21718757
J Neurosci Methods. 2012 Mar 30;205(1):49-64
22226741
Hippocampus. 2012 Jul;22(7):1508-16
22271231
Annu Rev Physiol. 1999;61:497-519
10099699
Cell Tissue Res. 2015 Jul;361(1):95-114
25874597
J Neurosci. 2011 Sep 21;31(38):13386-99
21940432
Hear Res. 2010 Dec 1;270(1-2):119-26
20813177
Front Neural Circuits. 2012 Oct 05;6:71
23060752
J Comp Neurol. 1986 Feb 22;244(4):533-49
2420837
Proc Natl Acad Sci U S A. 2012 Oct 30;109(44):18138-43
23074252
J Proteomics. 2013 Feb 21;79:43-59
23201114
Neuron. 1995 Oct;15(4):875-84
7576636
J Neurosci. 2009 Nov 4;29(44):13770-84
19889989
Neurosci Lett. 2000 Jun 23;287(2):161-5
10854736
Nat Neurosci. 2012 Nov;15(11):1531-8
23042081
J Neurosci. 2011 Jun 1;31(22):8280-94
21632949
Trends Neurosci. 2005 Jun;28(6):290-6
15927684
J Neurophysiol. 2011 Sep;106(3):1443-53
21697449
J Neurophysiol. 2008 Oct;100(4):1724-39
18667546
Front Neural Circuits. 2014 Oct 01;8:116
25324726
J Neurosci. 1994 May;14(5 Pt 2):3246-62
8182469
J Neurosci. 2005 Dec 14;25(50):11676-83
16354926
J Neurosci. 2011 Nov 16;31(46):16637-50
22090491
Exp Brain Res. 1993;95(2):223-39
8224048
J Neurosci. 2001 Sep 1;21(17):6666-72
11517256
Neuroreport. 2000 Nov 27;11(17):3709-13
11117477
J Neurosci. 1999 Mar 1;19(5):1557-65
10024343
Neuron. 1999 Jun;23(2):399-409
10399944
Neuron. 1998 Apr;20(4):797-807
9581770
Neuroscience. 2008 Jun 12;154(1):160-70
18436383
Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6896-900
7624339
J Comp Neurol. 1985 Aug 15;238(3):249-62
4044914
J Comp Neurol. 1996 Jan 29;365(1):141-58
8821447
J Physiol. 2007 Jun 1;581(Pt 2):581-602
17347264