GABABR silencing of nerve terminals

Abstract
Data availability
Article and author information
Metrics

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).

The following data sets were generated

1. Ryan TA
2. Cook D
(2022) Supporting Data
Dryad Digital Repository, doi:10.5061/dryad.1zcrjdfw0.

https://dx.doi.org/10.5061/dryad.1zcrjdfw0

Article and author information

Author details

Daniel Charles Cook

Department of Anesthesiology, Weill Cornell Medical College, New York, United States

Competing interests
The authors declare that no competing interests exist.
Timothy Aidan Ryan

Department of Biochemistry, Weill Cornell Medical College, New York, Norway

For correspondence
taryan@med.cornell.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2533-9548

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

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.