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

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. Synopsis A chemosensory neuron in Caenorhabditis elegans shows remarkable computational capacities to efficiently encode external stimuli. A TAX‐6‐mediated negative feedback loop within the GPCR signaling pathway underlies these computational capacities. A negative feedback in the GPCR signaling pathway supports several coding functions in a cell‐autonomous manner. TAX‐6/Calcineurin mediates a calcium‐dependent negative feedback to support adaptation to the first derivative of gradients and exact adaptation. A parsimonious mathematical model recapitulates the cell‐autonomous coding features. Graphical Abstract A chemosensory neuron in Caenorhabditis elegans shows remarkable computational capacities to efficiently encode external stimuli. A TAX‐6‐mediated negative feedback loop within the GPCR signaling pathway underlies these computational capacities.