Cholinergic transmission in C. elegans: Functions, diversity, and maturation of ACh-activated ion channels

J Neurochem. 2021 Sep;158(6):1274-1291. doi: 10.1111/jnc.15164. Epub 2020 Sep 25.

Abstract

Acetylcholine is an abundant neurotransmitter in all animals. Effects of acetylcholine are excitatory, inhibitory, or modulatory depending on the receptor and cell type. Research using the nematode C. elegans has made ground-breaking contributions to the mechanistic understanding of cholinergic transmission. Powerful genetic screens for behavioral mutants or for responses to pharmacological reagents identified the core cellular machinery for synaptic transmission. Pharmacological reagents that perturb acetylcholine-mediated processes led to the discovery and also uncovered the composition and regulators of acetylcholine-activated channels and receptors. From a combination of electrophysiological and molecular cellular studies, we have gained a profound understanding of cholinergic signaling at the levels of synapses, neural circuits, and animal behaviors. This review will begin with a historical overview, then cover in-depth current knowledge on acetylcholine-activated ionotropic receptors, mechanisms regulating their functional expression and their functions in regulating locomotion.

Keywords: ACR genes; RIC-3; acetylcholine; aldicarb; cys-loop receptors; excitation and inhibition balance; levamisole; locomotion; motor neurons; nAChRs; synapse.

Publication types

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

MeSH terms

  • Acetylcholine / genetics
  • Acetylcholine / metabolism*
  • Acetylcholine / pharmacology
  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Caenorhabditis elegans Proteins / physiology
  • Cholinergic Agents / metabolism
  • Cholinergic Agents / pharmacology
  • Humans
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology*
  • Locomotion / physiology*
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology
  • Receptors, Cholinergic / genetics
  • Receptors, Cholinergic / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*

Substances

  • Caenorhabditis elegans Proteins
  • Cholinergic Agents
  • Receptors, Cholinergic
  • Acetylcholine