Evoked and Spontaneous Transmission Favored by Distinct Sets of Synapses

Overview

Journal Curr Biol

Publisher Cell Press

Specialty Biology

Date 2014 Feb 25

PMID 24560571

Citations 82

Authors

Einat S Peled

Zachary L Newman

Ehud Y Isacoff

Affiliations

Soon will be listed here.

Abstract

Background: Spontaneous "miniature" transmitter release takes place at low rates at all synapses. Long thought of as an unavoidable leak, spontaneous release has recently been suggested to be mediated by distinct pre- and postsynaptic molecular machineries and to have a specialized role in setting up and adjusting neuronal circuits. It remains unclear how spontaneous and evoked transmission are related at individual synapses, how they are distributed spatially when an axon makes multiple contacts with a target, and whether they are commonly regulated.

Results: Electrophysiological recordings in the Drosophila larval neuromuscular junction, in the presence of the use-dependent glutamate receptor (GluR) blocker philanthotoxin, indicated that spontaneous and evoked transmission employ distinct sets of GluRs. In vivo imaging of transmission using synaptically targeted GCaMP3 to detect Ca(2+) influx through the GluRs revealed little spatial overlap between synapses participating in spontaneous and evoked transmission. Spontaneous and evoked transmission were oppositely correlated with presynaptic levels of the protein Brp: synapses with high Brp favored evoked transmission, whereas synapses with low Brp were more active spontaneously. High-frequency stimulation did not increase the overlap between evoked and spontaneous transmission, and instead decreased the rate of spontaneous release from synapses that were highly active in evoked transmission.

Conclusions: Although individual synapses can participate in both evoked and spontaneous transmission, highly active synapses show a preference for one mode of transmission. The presynaptic protein Brp promotes evoked transmission and suppresses spontaneous release. These findings suggest the existence of presynaptic mechanisms that promote synaptic specialization to either evoked or spontaneous transmission.

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References

Eldefrawi A, Eldefrawi M, Konno K, Mansour N, Nakanishi K, Oltz E . Structure and synthesis of a potent glutamate receptor antagonist in wasp venom. Proc Natl Acad Sci U S A. 1988; 85(13):4910-3. PMC: 280547. DOI: 10.1073/pnas.85.13.4910. View

Zenisek D . Vesicle association and exocytosis at ribbon and extraribbon sites in retinal bipolar cell presynaptic terminals. Proc Natl Acad Sci U S A. 2008; 105(12):4922-7. PMC: 2290766. DOI: 10.1073/pnas.0709067105. View

FATT P, Katz B . Spontaneous subthreshold activity at motor nerve endings. J Physiol. 1952; 117(1):109-28. PMC: 1392564. View

Cattaert D, Birman S . Blockade of the central generator of locomotor rhythm by noncompetitive NMDA receptor antagonists in Drosophila larvae. J Neurobiol. 2001; 48(1):58-73. DOI: 10.1002/neu.1042. View

Hallermann S, Kittel R, Wichmann C, Weyhersmuller A, Fouquet W, Mertel S . Naked dense bodies provoke depression. J Neurosci. 2010; 30(43):14340-5. PMC: 6634796. DOI: 10.1523/JNEUROSCI.2495-10.2010. View

Pang Z, Sun J, Rizo J, Maximov A, Sudhof T . Genetic analysis of synaptotagmin 2 in spontaneous and Ca2+-triggered neurotransmitter release. EMBO J. 2006; 25(10):2039-50. PMC: 1462977. DOI: 10.1038/sj.emboj.7601103. View

Del Castillo J, Katz B . Quantal components of the end-plate potential. J Physiol. 1954; 124(3):560-73. PMC: 1366292. DOI: 10.1113/jphysiol.1954.sp005129. View

Zucker R . Minis: whence and wherefore?. Neuron. 2005; 45(4):482-4. DOI: 10.1016/j.neuron.2005.02.003. View

Xu J, Pang Z, Shin O, Sudhof T . Synaptotagmin-1 functions as a Ca2+ sensor for spontaneous release. Nat Neurosci. 2009; 12(6):759-66. PMC: 2739891. DOI: 10.1038/nn.2320. View

10.

Ramirez D, Kavalali E . Differential regulation of spontaneous and evoked neurotransmitter release at central synapses. Curr Opin Neurobiol. 2011; 21(2):275-82. PMC: 3092808. DOI: 10.1016/j.conb.2011.01.007. View

11.

Graf E, Daniels R, Burgess R, Schwarz T, DiAntonio A . Rab3 dynamically controls protein composition at active zones. Neuron. 2009; 64(5):663-77. PMC: 2796257. DOI: 10.1016/j.neuron.2009.11.002. View

12.

Yoshihara M, Adolfsen B, Galle K, Littleton J . Retrograde signaling by Syt 4 induces presynaptic release and synapse-specific growth. Science. 2005; 310(5749):858-63. DOI: 10.1126/science.1117541. View

13.

Melom J, Akbergenova Y, Gavornik J, Littleton J . Spontaneous and evoked release are independently regulated at individual active zones. J Neurosci. 2013; 33(44):17253-63. PMC: 3812501. DOI: 10.1523/JNEUROSCI.3334-13.2013. View

14.

Zhai R, Bellen H . The architecture of the active zone in the presynaptic nerve terminal. Physiology (Bethesda). 2004; 19:262-70. DOI: 10.1152/physiol.00014.2004. View

15.

DiAntonio A, Schwarz T . The effect on synaptic physiology of synaptotagmin mutations in Drosophila. Neuron. 1994; 12(4):909-20. DOI: 10.1016/0896-6273(94)90342-5. View

16.

Owald D, Fouquet W, Schmidt M, Wichmann C, Mertel S, Depner H . A Syd-1 homologue regulates pre- and postsynaptic maturation in Drosophila. J Cell Biol. 2010; 188(4):565-79. PMC: 2828917. DOI: 10.1083/jcb.200908055. View

17.

Wagh D, Rasse T, Asan E, Hofbauer A, Schwenkert I, Durrbeck H . Bruchpilot, a protein with homology to ELKS/CAST, is required for structural integrity and function of synaptic active zones in Drosophila. Neuron. 2006; 49(6):833-44. DOI: 10.1016/j.neuron.2006.02.008. View

18.

Karst H, Piek T, van Marle J, Lind A . Structure-activity relationship of philanthotoxins--I. Pre- and postsynaptic inhibition of the locust neuromuscular transmission. Comp Biochem Physiol C Comp Pharmacol Toxicol. 1991; 98(2-3):471-7. DOI: 10.1016/0742-8413(91)90236-m. View

19.

Frank C, Kennedy M, Goold C, Marek K, Davis G . Mechanisms underlying the rapid induction and sustained expression of synaptic homeostasis. Neuron. 2006; 52(4):663-77. PMC: 2673733. DOI: 10.1016/j.neuron.2006.09.029. View

20.

Sara Y, Bal M, Adachi M, Monteggia L, Kavalali E . Use-dependent AMPA receptor block reveals segregation of spontaneous and evoked glutamatergic neurotransmission. J Neurosci. 2011; 31(14):5378-82. PMC: 3086544. DOI: 10.1523/JNEUROSCI.5234-10.2011. View