Rapid multi-directed cholinergic transmission in the central nervous system

Santhosh Sethuramanujam, Akihiro Matsumoto, Geoff deRosenroll, Benjamin Murphy-Baum, Claudio F Grosman, J. Michael McIntosh, Miao Jing, Yulong Li, David Berson, Keisuke Yonehara, Gautam B. Awatramani

Research output: Contribution to journalArticlepeer-review


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 µm 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.

Original languageEnglish (US)
Article number1374
JournalNature communications
Issue number1
StatePublished - Mar 2021

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


Dive into the research topics of 'Rapid multi-directed cholinergic transmission in the central nervous system'. Together they form a unique fingerprint.

Cite this