First Author | Sethuramanujam S | Year | 2021 |
Journal | Nat Commun | Volume | 12 |
Issue | 1 | Pages | 1374 |
PubMed ID | 33654091 | Mgi Jnum | J:349383 |
Mgi Id | MGI:6515142 | Doi | 10.1038/s41467-021-21680-9 |
Citation | Sethuramanujam S, et al. (2021) Rapid multi-directed cholinergic transmission in the central nervous system. Nat Commun 12(1):1374 |
abstractText | 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 (~1 ms) co-activates receptors expressed in multiple neurons located within ~1 microm 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. |