Rapid multi-directed cholinergic transmission in the central nervous system

Nat Commun. 2021 Mar 2;12(1):1374. doi: 10.1038/s41467-021-21680-9.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism*
  • Amacrine Cells / physiology
  • Amacrine Cells / ultrastructure
  • Animals
  • Central Nervous System / physiology*
  • Dendrites / physiology
  • Dendrites / ultrastructure
  • Kinetics
  • Mice
  • Mice, Inbred C57BL
  • Photons
  • Retinal Ganglion Cells / ultrastructure
  • Synaptic Transmission / physiology*

Substances

  • Acetylcholine