Rapid multi-directed cholinergic transmission in the central nervous system

In many parts of the central nervous system, including the retina, it is unclear whether cholinergic transmission is mediated by rapid, point-to-point synaptic mechanisms, or slower, broad-scale 'non-synaptic' mechanisms. Here, we characterized the ultrastructural features of cholinergic connections between direction-selective starburst amacrine cells and downstream ganglion cells in an existing serial electron microscopy data set, as well as their functional properties using electrophysiology and two-photon acetylcholine (ACh) imaging. Correlative results demonstrate that a 'tripartite' structure facilitates a 'multi-directed' form of transmission, in which ACh released from a single vesicle rapidly (similar to 1ms) co-activates receptors expressed in multiple neurons located within similar to 1 mu m of the release site. Cholinergic signals are direction-selective at a local, but not global scale, and facilitate the transfer of information from starburst to ganglion cell dendrites. These results suggest a distinct operational framework for cholinergic signaling that bears the hallmarks of synaptic and non-synaptic forms of transmission.

Automated summary

The study reveals that acetylcholine signals are transmitted through a rapid co-activation mechanism, activating receptors on multiple neurons surrounding the release site. Additionally, while acetylcholine signals are direction-selective locally, they do not show global directionality, facilitating information transfer at a local scale.