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

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 ?m. 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.

SUBMITTER: Zhu PK 

PROVIDER: S-EPMC7519949 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature