RT Journal Article SR Electronic T1 A GPCR negative feedback loop underlies efficient coding of external stimuli JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.12.14.422627 DO 10.1101/2020.12.14.422627 A1 Rotem Ruach A1 Shai Yellinek A1 Eyal Itskovits A1 Alon Zaslaver YR 2020 UL http://biorxiv.org/content/early/2020/12/14/2020.12.14.422627.abstract AB Efficient navigation based on chemical cues is an essential feature shared by all animals. These cues may be encountered in complex spatio-temporal 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 C. elegans worms 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 GPCR signaling pathway in which TAX-6/Calcineurin plays a key role in mediating the feedback inhibition. Crucially, this negative feedback pathway 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 accurately captured the fine neural dynamics of both wt 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 universal solution for efficient cell-autonomous coding of external stimuli.Competing Interest StatementThe authors have declared no competing interest.