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Christine Damrau1, Naoko Toshima2, Teiichi Tanimura2 (0000-0001-5730-8848), Björn Brembs*,1,3 (0000-0001-7824-7650), Julien Colomb1 (0000-0002-3127-5520)

1Freie Universität Berlin, Fachbereich Biologie-Chemie-Pharmazie, Institut für Biologie, Neurobiologie, Königin-Luise-Straße 28-30, 14195 Berlin, Germany

2Kyushu University, Division of Biological Sciences, Graduate School of Systems Life Sciences, Hakozaki, Fukuoka 812-8581, Japan

3University of Regensburg, Institute of Zoology – Neurogenetics, Universitätsstraße 31, 93040 Regensburg, Germany

* Corresponding author, bjoern@brembs.net

All animals constantly negotiate external with internal demands before and during action selection. Energy homeostasis is a major internal factor biasing action selection. For instance, in addition to physiologically regulating carbohydrate mobilization, starvation-induced sugar shortage also biases action selection towards food-seeking and food consumption behaviors (the counter-regulatory response). Biogenic amines are often involved when such widespread behavioral biases need to be orchestrated. In mammals, norepinephrine (noradrenalin) is involved in the counterregulatory response to starvation-induced drops in glucose levels. The invertebrate homologue of noradrenalin, octopamine (OA) and its precursor tyramine (TA) are neuromodulators operating in many different neuronal and physiological processes. We investigated the role of those two transmitters in Drosophila sugar responsiveness. Tyrosine-ß-hydroxylase (tßh) mutants are unable to convert TA into OA. Starved mutants show a reduced sugar response and their hemolymph sugar concentration is elevated compared to control flies. When starved, they survive longer. Temporally controlled rescue experiments revealed an action of the OA/TA-system during the sugar response, while spatially controlled rescue experiments suggest actions also outside of the nervous system. Additionally, the analysis of two OA- and four TA-receptor mutants suggests an involvement of both receptor types in the animals' physiological and neuronal response to starvation. These results complement the investigations in Apis mellifera described in our companion paper (Buckemüller et al.).


There may be more than just cultural value to the old German saying "grain tastes bitter for a satiated mouse" Sala 2013. Indeed, it is the state of an organism which determines what, if any, effect external sensory stimuli will have on the nervous system. Whether this is the satiation state of the mouse influencing taste receptors, or the feeding state of the leech which gates mechanosensory stimuli Gaudry 2010Gaudry 2009, or the locomotor state of flies which adjusts the gain in visual interneurons Chiappe 2010Maimon 2010Longden 2009Breugel 2014Tuthill 2014Suver 2012, sensory stimuli are rarely, if ever, directly transformed into motor outputs. Instead, all nervous systems seem to constantly balance external and internal demands before they arrive at any given action Brembs 2013Brembs 2017Heisenberg 2009Pezzulo 2016. Biogenic amines and neuropeptides have been shown to be crucially involved in orchestrating the processes needed to find this balance.