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Nanoscopic Visualization of Restricted Nonvolume Cholinergic and Monoaminergic Transmission with Genetically Encoded Sensors.

TitleNanoscopic Visualization of Restricted Nonvolume Cholinergic and Monoaminergic Transmission with Genetically Encoded Sensors.
Publication TypeJournal Article
Year of Publication2020
AuthorsZhu PK, W Zheng S, Zhang P, Jing M, Borden PM, Ali F, Guo K, Feng J, Marvin JS, Wang Y, Wan J, Gan L, Kwan AC, Lin L, Looger LL, Li Y, Zhang Y
JournalNano Lett
Volume20
Issue6
Pagination4073-4083
Date Published2020 Jun 10
ISSN1530-6992
Abstract

How neuromodulatory transmitters diffuse into the extracellular space remains an unsolved fundamental biological question, despite wide acceptance of the volume transmission model. Here, we report development of a method combining genetically encoded fluorescent sensors with high-resolution imaging and analysis algorithms which permits the first direct visualization of neuromodulatory transmitter diffusion at various neuronal and non-neuronal cells. Our analysis reveals that acetylcholine and monoamines diffuse at individual release sites with a spread length constant of ∼0.75 μm. These transmitters employ varied numbers of release sites, and when spatially close-packed release sites coactivate they can spillover into larger subcellular areas. Our data indicate spatially restricted (i.e., nonvolume) neuromodulatory transmission to be a prominent intercellular communication mode, reshaping current thinking of control and precision of neuromodulation crucial for understanding behaviors and diseases.

DOI10.1021/acs.nanolett.9b04877
Alternate JournalNano Lett.
PubMed ID32396366