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The probability of neurotransmitter release: variability and feedback control at single synapses

Abstract

Information transfer at chemical synapses occurs when vesicles fuse with the plasma membrane and release neurotransmitter. This process is stochastic and its likelihood of occurrence is a crucial factor in the regulation of signal propagation in neuronal networks. The reliability of neurotransmitter release can be highly variable: experimental data from electrophysiological, molecular and imaging studies have demonstrated that synaptic terminals can individually set their neurotransmitter release probability dynamically through local feedback regulation. This local tuning of transmission has important implications for current models of single-neuron computation.

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Figure 1: Characterizing neuronal connections with paired recordings and morphological reconstructions.
Figure 2: Variability of release probability measured at single synapses.
Figure 3: Postsynaptic influences on release probability.
Figure 4: Consequences of pr adjustments for signal/noise ratio and energy usage.

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Acknowledgements

We would like to thank D. Attwell, B. Clark, A. Roth and M. Häusser for critical comments on the manuscript, M. London for helpful discussions, and Y. Goda and M. Häusser for support. T.B. is supported by grants from the Wellcome Trust and the Gatsby Charitable Foundation (to M. Häusser). K.S. is supported by the Wellcome Trust (WT084357MF) and the Biotechnology and Biological Sciences Research Council (BB/F018371). We apologise to authors whose work we were unable to include owing to space constraints.

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Glossary

Active zone

A specialized area of the presynaptic membrane where synaptic vesicle exocytosis occurs.

Dendritic integration

The process through which synaptic inputs interact with each other and with the electrical properties of the dendritic tree to generate patterns of action potential output.

Gain control

Regulation of the relationship between synaptic input and neuronal output.

Miniature excitatory postsynaptic currents

The postsynaptic signals that are produced in response to spontaneous release of a single quantum of transmitter (usually a single vesicle).

Quantal analysis

A statistical approach for decomposing the synaptic response into the underlying quanta, usually involving estimation of quantal size, release probability and number of release sites.

Shunting

A decrease in the size of synaptic responses that results from an increase in the membrane conductance (for example, through neurotransmitter-activated ion channels).

Synaptic homeostasis

A regulatory process that stabilizes synaptic weights around a set point.

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Branco, T., Staras, K. The probability of neurotransmitter release: variability and feedback control at single synapses. Nat Rev Neurosci 10, 373–383 (2009). https://doi.org/10.1038/nrn2634

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