Rapid multi-directed cholinergic transmission in the central nervous system

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  • Santhosh Sethuramanujam, Victoria University
  • ,
  • Akihiro Matsumoto
  • Geoff deRosenroll, Victoria University
  • ,
  • Benjamin Murphy-Baum, Victoria University
  • ,
  • J. Michael McIntosh, University of Utah
  • ,
  • Miao Jing, Peking University
  • ,
  • Yulong Li, Peking University
  • ,
  • David Berson, Brown University
  • ,
  • Keisuke Yonehara
  • Gautam B. Awatramani, Victoria University

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
Article number1374
JournalNature Communications
Volume12
Issue1
Number of pages13
ISSN2041-1723
DOIs
Publication statusPublished - Mar 2021

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