Vesicular Release Probability Sets the Strength of Individual Schaffer Collateral Synapses

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Oct 17

PMID 36253353

Authors

Celine D Durst

J Simon Wiegert

Christian Schulze

Nordine Helassa

Katalin Torok

Thomas G Oertner

Affiliations

Soon will be listed here.

Abstract

Information processing in the brain is controlled by quantal release of neurotransmitters, a tightly regulated process. From ultrastructural analysis, it is known that presynaptic boutons along single axons differ in the number of vesicles docked at the active zone. It is not clear whether the probability of these vesicles to get released (p) is homogenous or also varies between individual boutons. Here, we optically measure evoked transmitter release at individual Schaffer collateral synapses at different calcium concentrations, using the genetically encoded glutamate sensor iGluSnFR. Fitting a binomial model to measured response amplitude distributions allowed us to extract the quantal parameters N, p, and q. We find that Schaffer collateral boutons typically release single vesicles under low p conditions and switch to multivesicular release in high calcium saline. The potency of individual boutons is highly correlated with their vesicular release probability while the number of releasable vesicles affects synaptic output only under high p conditions.

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References

Imig C, Min S, Krinner S, Arancillo M, Rosenmund C, Sudhof T . The morphological and molecular nature of synaptic vesicle priming at presynaptic active zones. Neuron. 2014; 84(2):416-31. DOI: 10.1016/j.neuron.2014.10.009. View

Nimchinsky E, Yasuda R, Oertner T, Svoboda K . The number of glutamate receptors opened by synaptic stimulation in single hippocampal spines. J Neurosci. 2004; 24(8):2054-64. PMC: 6730404. DOI: 10.1523/JNEUROSCI.5066-03.2004. View

Oertner T, Sabatini B, Nimchinsky E, Svoboda K . Facilitation at single synapses probed with optical quantal analysis. Nat Neurosci. 2002; 5(7):657-64. DOI: 10.1038/nn867. View

Marvin J, Borghuis B, Tian L, Cichon J, Harnett M, Akerboom J . An optimized fluorescent probe for visualizing glutamate neurotransmission. Nat Methods. 2013; 10(2):162-70. PMC: 4469972. DOI: 10.1038/nmeth.2333. View

Hu Y, Qu L, Schikorski T . Mean synaptic vesicle size varies among individual excitatory hippocampal synapses. Synapse. 2008; 62(12):953-7. DOI: 10.1002/syn.20567. View

Wiegert J, Gee C, Oertner T . Single-Cell Electroporation of Neurons. Cold Spring Harb Protoc. 2017; 2017(2). DOI: 10.1101/pdb.prot094904. View

Rusakov D, Savtchenko L, Zheng K, Henley J . Shaping the synaptic signal: molecular mobility inside and outside the cleft. Trends Neurosci. 2011; 34(7):359-69. PMC: 3133640. DOI: 10.1016/j.tins.2011.03.002. View

Jonas P, Major G, Sakmann B . Quantal components of unitary EPSCs at the mossy fibre synapse on CA3 pyramidal cells of rat hippocampus. J Physiol. 1993; 472:615-63. PMC: 1160505. DOI: 10.1113/jphysiol.1993.sp019965. View

Ding F, ODonnell J, Xu Q, Kang N, Goldman N, Nedergaard M . Changes in the composition of brain interstitial ions control the sleep-wake cycle. Science. 2016; 352(6285):550-5. PMC: 5441687. DOI: 10.1126/science.aad4821. View

10.

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

11.

Soares C, Trotter D, Longtin A, Beique J, Naud R . Parsing Out the Variability of Transmission at Central Synapses Using Optical Quantal Analysis. Front Synaptic Neurosci. 2019; 11:22. PMC: 6702664. DOI: 10.3389/fnsyn.2019.00022. View

12.

Mainen Z, Malinow R, Svoboda K . Synaptic calcium transients in single spines indicate that NMDA receptors are not saturated. Nature. 1999; 399(6732):151-5. DOI: 10.1038/20187. View

13.

Dobrunz L, Stevens C . Heterogeneity of release probability, facilitation, and depletion at central synapses. Neuron. 1997; 18(6):995-1008. DOI: 10.1016/s0896-6273(00)80338-4. View

14.

Nadkarni S, Bartol T, Stevens C, Sejnowski T, Levine H . Short-term plasticity constrains spatial organization of a hippocampal presynaptic terminal. Proc Natl Acad Sci U S A. 2012; 109(36):14657-62. PMC: 3437845. DOI: 10.1073/pnas.1211971109. View

15.

Qu L, Akbergenova Y, Hu Y, Schikorski T . Synapse-to-synapse variation in mean synaptic vesicle size and its relationship with synaptic morphology and function. J Comp Neurol. 2009; 514(4):343-52. DOI: 10.1002/cne.22007. View

16.

Bolshakov V, Golan H, Kandel E, Siegelbaum S . Recruitment of new sites of synaptic transmission during the cAMP-dependent late phase of LTP at CA3-CA1 synapses in the hippocampus. Neuron. 1997; 19(3):635-51. DOI: 10.1016/s0896-6273(00)80377-3. View

17.

Frerking M, Wilson M . Saturation of postsynaptic receptors at central synapses?. Curr Opin Neurobiol. 1996; 6(3):395-403. DOI: 10.1016/s0959-4388(96)80125-5. View

18.

Durst C, Wiegert J, Schulze C, Helassa N, Torok K, Oertner T . Vesicular release probability sets the strength of individual Schaffer collateral synapses. Nat Commun. 2022; 13(1):6126. PMC: 9576736. DOI: 10.1038/s41467-022-33565-6. View

19.

Tong G, Jahr C . Multivesicular release from excitatory synapses of cultured hippocampal neurons. Neuron. 1994; 12(1):51-9. DOI: 10.1016/0896-6273(94)90151-1. View

20.

Rose T, Schoenenberger P, Jezek K, Oertner T . Developmental refinement of vesicle cycling at Schaffer collateral synapses. Neuron. 2013; 77(6):1109-21. DOI: 10.1016/j.neuron.2013.01.021. View