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Facilitation at single synapses probed with optical quantal analysis

Abstract

Many synapses can change their strength rapidly in a use-dependent manner, but the mechanisms of such short-term plasticity remain unknown. To understand these mechanisms, measurements of neurotransmitter release at single synapses are required. We probed transmitter release by imaging transient increases in [Ca2+] mediated by synaptic N-methyl-D-aspartate receptors (NMDARs) in individual dendritic spines of CA1 pyramidal neurons in rat brain slices, enabling quantal analysis at single synapses. We found that changes in release probability, produced by paired-pulse facilitation (PPF) or by manipulation of presynaptic adenosine receptors, were associated with changes in glutamate concentration in the synaptic cleft, indicating that single synapses can release a variable amount of glutamate per action potential. The relationship between release probability and response size is consistent with a binomial model of vesicle release with several (>5) independent release sites per active zone, suggesting that multivesicular release contributes to facilitation at these synapses.

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Figure 1: Measurement of NMDAR-mediated [Ca2+] transients in single spines.
Figure 2: Paired-pulse facilitation of excitatory postsynaptic currents.
Figure 3: Paired-pulse facilitation at a single synapse.
Figure 4: Dissecting PPF in individual synapses.
Figure 5: Varying release probability pharmacologically changes potency.
Figure 6: Rise times of [Ca2+] transients under control and potentiated conditions.
Figure 7: Change in potency is constant as a function of holding potential.

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Acknowledgements

We thank Z. Mainen, R. Malinow, M. Maravall and R. Yasuda for comments on the manuscript, and T. Pologruto for software development. This work was supported by grants from the Swartz Initiative for Computational Neuroscience (to T.G.O.), the Helen Hay Whitney Foundation (to B.L.S.), the Pew and Mathers Foundations and the National Institutes of Health (NIH).

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Correspondence to Karel Svoboda.

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Oertner, T., Sabatini, B., Nimchinsky, E. et al. Facilitation at single synapses probed with optical quantal analysis. Nat Neurosci 5, 657–664 (2002). https://doi.org/10.1038/nn867

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