Modulation of neuronal activity in the Drosophila mushroom body by DopEcR, a unique dual receptor for ecdysone and dopamine

Abstract

G-protein-coupled receptors (GPCRs) for steroid hormones mediate unconventional steroid signaling and play a significant role in the rapid actions of steroids in a variety of biological processes, including those in the nervous system. However, the effects of these GPCRs on overall neuronal activity remain largely elusive. Drosophila DopEcR is a GPCR that responds to both ecdysone (the major steroid hormone in insects) and dopamine, regulating multiple second messenger systems. Recent studies have revealed that DopEcR is preferentially expressed in the nervous system and involved in behavioral regulation. Here we utilized the bioluminescent Ca-indicator GFP-aequorin to monitor the nicotine-induced Ca-response within the mushroom bodies (MB), a higher-order brain center in flies, and examined how DopEcR modulates these Ca-dynamics. Our results show that in DopEcR knockdown flies, the nicotine-induced Ca-response in the MB was significantly enhanced selectively in the medial lobes. We then reveal that application of DopEcR's ligands, ecdysone and dopamine, had different effects on nicotine-induced Ca-responses in the MB: ecdysone enhanced activity in the calyx and cell body region in a DopEcR-dependent manner, whereas dopamine reduced activity in the medial lobes independently of DopEcR. Finally, we show that flies with reduced DopEcR function in the MB display decreased locomotor activity. This behavioral phenotype of DopEcR-deficient flies may be partly due to their enhanced MB activity, since the MB have been implicated in the suppression of locomotor activity. Overall, these data suggest that DopEcR is involved in region-specific modulation of Ca dynamics within the MB, which may play a role in behavioral modulation.

Neurochemical Organization of the Drosophila Brain Visualized by Endogenously Tagged Neurotransmitter Receptors

“…Similar compartmental localization was observed at the base of many axon tracts, suggesting AIS localization of DopEcR::Venus in other cell types (data not shown). Because action potentials are generated in the AIS, DopEcR might control signal propagation in response to dopamine and/ or ecdysteroids by modulating spike initiation (Lark et al, 2017). Taken together, our results demonstrate that localization of dopamine receptors divide the cell membrane into spatially distinct compartments, which might allow single neurons respond differently depending on the site of dopamine input.…”

Come Fly with Me: An overview of dopamine receptors in Drosophila melanogaster

“…The application of ecdysone increases nicotine‐induced Ca 2+ in the calyx and cell body region of the MB, whereas the application of DA increases Ca 2+ influx in response to sugar in gustatory receptor neurons. In both cases, the increase in Ca 2+ influx was dependent on DopEcR …”

Identification ofFoxPcircuits involved in locomotion and object fixation inDrosophila

“…The insect mushroom-bodies (MBs) are not only known as a center for olfactory learning and memory (Dolan et al, 2018;Felsenberg et al, 2018;König et al, 2019;Lyutova et al, 2019;Thum and Gerber, 2019;Turrel et al, 2018;e.g., Warth Pérez Arias et al, 2020;Widmer et al, 2018), they are also involved in the temporal and spatial control of locomotor activity (Besson and Martin, 2005;Helfrich-Förster et al, 2002;Lark et al, 2017;Lebreton and Martin, 2009;Mabuchi et al, 2016;Manjila et al, 2019;e.g., Martin et al, 1998;Serway et al, 2009;Sun et al, 2018;Xiong et al, 2010). In addition, (Castells-Nobau et al, 2019) (Fig.…”

“…The only case where only one set of parameters was affected were the FoxP 3955 mutant flies (Fig. 6) MBs have been shown to affect both spatial and temporal aspects of locomotion (Besson and Martin, 2005;Helfrich-Förster et al, 2002;Lark et al, 2017;Lebreton and Martin, 2009;Mabuchi et al, 2016;Manjila et al, 2019; e.g., Martin et al, 1998;Serway et al, 2009;Sun et al, 2018;Xiong et al, 2010) (Linneweber et al, 2020), but removing FoxP from DCNs showed no effect (Fig. 9B), despite abundant FoxP expression in DCNs (Fig.…”