Optimized design and in vivo application of optogenetically functionalized Drosophila dopamine receptors

Fangmin Zhou, Alexandra Madelaine Tichy, Bibi Nusreen Imambocus, Shreyas Sakharwade, Francisco J. Rodriguez Jimenez, Marco González Martínez, Ishrat Jahan, Margarita Habib, Nina Wilhelmy, Vanessa Burre, Tatjana Lömker, Kathrin Sauter, Charlotte Helfrich-Förster, Jan Pielage, Ilona C. Grunwald Kadow, Harald Janovjak, Peter Soba

Research output: Contribution to journalArticlepeer-review

Abstract

Neuromodulatory signaling via G protein-coupled receptors (GPCRs) plays a pivotal role in regulating neural network function and animal behavior. The recent development of optogenetic tools to induce G protein-mediated signaling provides the promise of acute and cell type-specific manipulation of neuromodulatory signals. However, designing and deploying optogenetically functionalized GPCRs (optoXRs) with accurate specificity and activity to mimic endogenous signaling in vivo remains challenging. Here we optimize the design of optoXRs by considering evolutionary conserved GPCR-G protein interactions and demonstrate the feasibility of this approach using two Drosophila Dopamine receptors (optoDopRs). These optoDopRs exhibit high signaling specificity and light sensitivity in vitro. In vivo, we show receptor and cell type-specific effects of dopaminergic signaling in various behaviors, including the ability of optoDopRs to rescue the loss of the endogenous receptors. This work demonstrates that optoXRs can enable optical control of neuromodulatory receptor-specific signaling in functional and behavioral studies.

Original languageEnglish
Article number8434
JournalNature Communications
Volume14
Issue number1
DOIs
StatePublished - Dec 2023

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