GABABR silencing of nerve terminals
Abstract
Control of neurotransmission efficacy is central to theories of how the brain computes and stores information. Presynaptic G-protein coupled receptors (GPCRs) are critical in this problem as they locally influence synaptic strength and can operate on a wide range of time scales. Among the mechanisms by which GPCRs impact neurotransmission is by inhibiting 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 GPCR 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.
Data availability
All data generated or analyzed during this study is included in the manuscript and supporting file; Source Data has been uploaded onto Dryad (doi:10.5061/dryad.1zcrjdfw0) and customized code has been uploaded to Github (https://github.com/taryan2020/ImageJ.git).
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Supporting DataDryad Digital Repository, doi:10.5061/dryad.1zcrjdfw0.
Article and author information
Author details
Funding
NINDS (NS036942)
- Timothy Aidan Ryan
NIGMS (GM148935)
- Daniel Charles Cook
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experiments involving animals were performed in accordance with protocols approved by the Weill Cornell Medicine Institutional Animal Care and Use Committee (IACUC protocol 0601-450A)
Copyright
© 2023, Cook & Ryan
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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