Octopamine and Tyramine Contribute Separately to the Counter-Regulatory Response to Sugar Deficit in Drosophila

Abstract

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 toward 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 homolog of noradrenalin, octopamine (OA) and its precursor tyramine (TA) are neuromodulators operating in many different neuronal and physiological processes. Tyrosine-ß-hydroxylase (tßh) mutants are unable to convert TA into OA. We hypothesized that tßh mutant flies may be aberrant in some or all of the counter-regulatory responses to starvation and that techniques restoring gene function or amine signaling may elucidate potential mechanisms and sites of action. Corroborating our hypothesis, 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., 2017).

Differential dominance of an allele of the Drosophila tßh gene challenges standard genetic techniques

“…We analyzed walking behavior in Buridan's paradigm (Bülthoff et al, 1982;Colomb et al, 2012), reporting both the median speed (a temporal measure of behavior) and stripe deviation (as a spatial measure assessing object fixation). The second experiment quantified sugar responsiveness after 20 h of starvation using proboscis extensions (Damrau et al, 2017b).…”

“…These results suggest that the standard genetic rescue approach can be successful at least in this phenotype, even with a pleiotropic gene. Some of us have shown previously that another phenotype, sugar sensitivity after starvation, can be similarly rescued (Damrau et al, 2017a). In the present work we studied tßh-associated differential dominance and rescue experiments using behavioral phenotypes as disparate as sugar sensitivity (Minnich, 1921;Dethier, 1976) and walking behavior in Buridan's paradigm (Bülthoff et al, 1982;Colomb et al, 2012).…”

“…Sugar response was measured as described elsewhere (Damrau et al, 2017b). Briefly, flies were starved for 20 h with Evian ® water.…”

“…All of those lines drive expression throughout development and in adulthood. Because we have already successfully used these techniques on sugar responsiveness (Damrau et al, 2017a), we focus on the walking measures from now on.…”

“…OA appears to be involved in almost every behavioral and physiological process (Libersat and Pflueger, 2004;Roeder, 2005). In Drosophila, the X-linked tßh nM18 mutant has been an important tool to understand the role of TA and OA in many behaviors such as egg-laying (Monastirioti et al, 1996;Lim et al, 2014;Li et al, 2015) , aggression (Zhou and Rao, 2008), flight (Brembs et al, 2007;Pflüger and Duch, 2011;Ryglewski et al, 2017;O'Sullivan et al, 2018), and sugar responsiveness (Damrau et al, 2017a).…”