@article{b99de607bea24ea6a60581adcf680c31,
title = "Behavioral state-dependent modulation of insulin-producing cells in Drosophila",
abstract = "Insulin signaling plays a pivotal role in metabolic control and aging, and insulin accordingly is a key factor in several human diseases. Despite this importance, the in vivo activity dynamics of insulin-producing cells (IPCs) are poorly understood. Here, we characterized the effects of locomotion on the activity of IPCs in Drosophila. Using in vivo electrophysiology and calcium imaging, we found that IPCs were strongly inhibited during walking and flight and that their activity rebounded and overshot after cessation of locomotion. Moreover, IPC activity changed rapidly during behavioral transitions, revealing that IPCs are modulated on fast timescales in behaving animals. Optogenetic activation of locomotor networks ex vivo, in the absence of actual locomotion or changes in hemolymph sugar levels, was sufficient to inhibit IPCs. This demonstrates that the behavioral state-dependent inhibition of IPCs is actively controlled by neuronal pathways and is independent of changes in glucose concentration. By contrast, the overshoot in IPC activity after locomotion was absent ex vivo and after starvation, indicating that it was not purely driven by feedforward signals but additionally required feedback derived from changes in hemolymph sugar concentration. We hypothesize that IPC inhibition during locomotion supports mobilization of fuel stores during metabolically demanding behaviors, while the rebound in IPC activity after locomotion contributes to replenishing muscle glycogen stores. In addition, the rapid dynamics of IPC modulation support a potential role of insulin in the state-dependent modulation of sensorimotor processing.",
keywords = "Drosophila, calcium imaging, electrophysiology, insulin, locomotion, metabolism, neuromodulation, state dependence",
author = "Sander Liessem and Martina Held and Bisen, {Rituja S.} and Hannah Haberkern and Haluk Lacin and Till Bockem{\"u}hl and Ache, {Jan M.}",
note = "Funding Information: This work was supported by a grant from the Deutsche Forschungsgemeinschaft to J.M.A. via the Emmy Noether program (DFG AC 371/1-1) and by a grant from the Deutsche Forschungsgemeinschaft to J.M.A. as part of the NSF/CIHR/DFG/FRQ/UKRI-MRC Next Generation Networks for Neuroscience (Neuronex) Program (DFG AC 371/2-1). T.B. is supported by Neuronex grant BU 857/15-1 from the Deutsche Forschungsgemeinschaft, and H.L. is supported by the National Institutes of Health grant NS122903. We thank Konrad {\"O}chsner (Julius-Maximilians-Universit{\"a}t of W{\"u}rzburg [JMU], Germany) and Michael D{\"u}bbert and Mehrdad Ghanbari (University of Cologne [UoC], Germany) for technical assistance; Charlotte F{\"o}rster and Wolfgang R{\"o}ssler (both JMU), Ansgar B{\"u}schges (UoC), Vivek Jayaraman (HHMI Janelia Research Campus, USA), and James W. Truman (Friday Harbor Laboratories, University of Washington, USA) for sharing resources; Jan A. Veenstra (University of Bordeaux, France) for providing the DILP-2 antibody; Dirk Rieger (JMU) for help setting up our lab in W{\"u}rzburg; Christian Wegener and Meet Zandawala (both JMU) for comments on an earlier version of the manuscript; and Tanja Godenschwege (Florida Atlantic University, USA) for help with the ex vivo preparations and comments on an earlier version of the manuscript. Conceptualization, S.L. and J.M.A.; experimental design, S.L. and J.M.A.; methodology, S.L. T.B. and J.M.A.; software, S.L. H.H. T.B. and J.M.A.; formal analysis, S.L. M.H. and J.M.A.; investigation, S.L. M.H. R.S.B. and J.M.A.; resources, H.L. T.B. and J.M.A.; writing – original draft, S.L. and J.M.A.; writing – review & editing, S.L. M.H. R.S.B. H.H. H.L. T.B. and J.M.A.; visualization, S.L. M.H. and J.M.A; supervision, J.M.A.; project administration, J.M.A; funding acquisition, J.M.A. The authors declare no competing interests. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in their field of research or within their geographical location. One or more of the authors of this paper self-identifies as a gender minority in their field of research. One or more of the authors of this paper self-identifies as living with a disability. We support inclusive, diverse, and equitable conduct of research. Funding Information: This work was supported by a grant from the Deutsche Forschungsgemeinschaft to J.M.A. via the Emmy Noether program (DFG AC 371/1-1 ) and by a grant from the Deutsche Forschungsgemeinschaft to J.M.A. as part of the NSF/CIHR/DFG/FRQ/UKRI-MRC Next Generation Networks for Neuroscience (Neuronex) Program (DFG AC 371/2-1 ). T.B. is supported by Neuronex grant BU 857/15-1 from the Deutsche Forschungsgemeinschaft , and H.L. is supported by the National Institutes of Health grant NS122903 . We thank Konrad {\"O}chsner (Julius-Maximilians-Universit{\"a}t of W{\"u}rzburg [JMU], Germany) and Michael D{\"u}bbert and Mehrdad Ghanbari (University of Cologne [UoC], Germany) for technical assistance; Charlotte F{\"o}rster and Wolfgang R{\"o}ssler (both JMU), Ansgar B{\"u}schges (UoC), Vivek Jayaraman (HHMI Janelia Research Campus, USA), and James W. Truman (Friday Harbor Laboratories, University of Washington, USA) for sharing resources; Jan A. Veenstra (University of Bordeaux, France) for providing the DILP-2 antibody; Dirk Rieger (JMU) for help setting up our lab in W{\"u}rzburg; Christian Wegener and Meet Zandawala (both JMU) for comments on an earlier version of the manuscript; and Tanja Godenschwege (Florida Atlantic University, USA) for help with the ex vivo preparations and comments on an earlier version of the manuscript. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2023",
month = feb,
day = "6",
doi = "10.1016/j.cub.2022.12.005",
language = "English",
volume = "33",
pages = "449--463.e5",
journal = "Current Biology",
issn = "0960-9822",
number = "3",
}