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bioRxiv · 10.1101/2022.09.16.508300

Neuromodulatory silencing of nerve terminals

Cook, D. C.·Ryan, T. A.
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Abstract

Control of neurotransmission efficacy is central to theories of how the brain computes and stores information. Neuromodulators are critical in this problem as they locally influence synaptic strength and can operate on a wide range of time scales. Presynaptic function is heavily influenced by G-protein coupled receptors (GPCRs) that in part restrict voltage-gated calcium (Ca2+) influx in the active zone. Here, using quantitative analysis of both single bouton Ca2+ influx and exocytosis, we uncovered an unexpected non-linear relationship between the magnitude of action potential driven Ca2+ influx and the concentration of external Ca2+ ([Ca2+]e). We find that this unexpected relationship is leveraged by neuromodulator signaling when operating at the nominal physiological set point for [Ca2+]e, 1.2 mM, to achieve complete silencing of nerve terminals. These data imply that the information throughput in neural circuits can be readily modulated in an all-or none fashion at the single synapse level when operating at the physiological set point.

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Cook, D. C., Ryan, T. A.. 2022-09-17. Neuromodulatory silencing of nerve terminals. https://doi.org/10.1101/2022.09.16.508300

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