A negative feedback loop in the GPCR pathway underlies efficient coding of external stimuli

Rotem Ruach, Shai Yellinek, Eyal Itskovits, Noa Deshe, Yifat Eliezer, Eduard Bokman, Alon Zaslaver*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Efficient navigation based on chemical cues is an essential feature shared by all animals. These cues may be encountered in complex spatiotemporal patterns and with orders of magnitude varying intensities. Nevertheless, sensory neurons accurately extract the relevant information from such perplexing signals. Here, we show how a single sensory neuron in Caenorhabditis elegans animals can cell-autonomously encode complex stimulus patterns composed of instantaneous sharp changes and of slowly changing continuous gradients. This encoding relies on a simple negative feedback in the G-protein-coupled receptor (GPCR) signaling pathway in which TAX-6/Calcineurin plays a key role in mediating the feedback inhibition. This negative feedback supports several important coding features that underlie an efficient navigation strategy, including exact adaptation and adaptation to the magnitude of the gradient's first derivative. A simple mathematical model explains the fine neural dynamics of both wild-type and tax-6 mutant animals, further highlighting how the calcium-dependent activity of TAX-6/Calcineurin dictates GPCR inhibition and response dynamics. As GPCRs are ubiquitously expressed in all sensory neurons, this mechanism may be a general solution for efficient cell-autonomous coding of external stimuli.

Original languageAmerican English
Article numbere10514
JournalMolecular Systems Biology
Issue number9
StatePublished - Sep 2022

Bibliographical note

Publisher Copyright:
© 2022 The Authors. Published under the terms of the CC BY 4.0 license.


  • GPCR signaling
  • calcineurin/TAX-6
  • calcium imaging
  • negative feedback
  • pulsatile response


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