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

Abstract

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.

Disposition of the chemosensory neurons in the neurotransmitter-release mutantunc-13

“…For microfluidic-based imaging, individual worms were inserted into a microfluidic chamber (Chronis et al, 2007) where they were partially anesthetized with 10 mM levamisole and left to habituate for 10 minutes (Bokman et al, 2024;Itskovits et al, 2018;Ruach et al, 2022). For the agar pad experiments a small think chuck of NGM agar was placed onto a slide.…”

Intricate response dynamics enhances stimulus discrimination in the resource-limitedC. eleganschemosensory system

“…In addition to population coding, response dynamics was also shown to be carrying important functional information. For example, pulsatile activity in the sensory neuron AWA underlies an efficient chemotactic navigation that allows animals to reach attractive cues faster (Itskovits et al 2018; Ruach et al 2022).…”