Octopamine mediates starvation-induced hyperactivity in adult Drosophila

Abstract

Starved animals often exhibit elevated locomotion, which has been speculated to partly resemble foraging behavior and facilitate food acquisition and energy intake. Despite its importance, the neural mechanism underlying this behavior remains unknown in any species. In this study we confirmed and extended previous findings that starvation induced locomotor activity in adult fruit flies Drosophila melanogaster. We also showed that starvationinduced hyperactivity was directed toward the localization and acquisition of food sources, because it could be suppressed upon the detection of food cues via both central nutrient-sensing and peripheral sweet-sensing mechanisms, via induction of food ingestion. We further found that octopamine, the insect counterpart of vertebrate norepinephrine, as well as the neurons expressing octopamine, were both necessary and sufficient for starvationinduced hyperactivity. Octopamine was not required for starvation-induced changes in feeding behaviors, suggesting independent regulations of energy intake behaviors upon starvation. Taken together, our results establish a quantitative behavioral paradigm to investigate the regulation of energy homeostasis by the CNS and identify a conserved neural substrate that links organismal metabolic state to a specific behavioral output.T he CNS plays an essential role in energy homeostasis (1). It actively monitors changes in the internal energy state and modulates an array of physiological and behavioral responses to enable energy homeostasis. Foraging behavior is critical for the localization and acquisition of food supply and hence energy homeostasis. It has been extensively documented both in ethological settings (2, 3) and under well-controlled laboratory conditions (4). Laboratory rodents with limited food access exhibit stereotypic food anticipatory activity (FAA) several hours before the mealtime, which is characterized by a steady increase in locomotion and other appetitive behaviors (5). The neural substrate that drives FAA still remains elusive (5, 6). Notably, the regulation of FAA seems to be dissociable from that of feeding behavior (7,8). These results hint at the presence of an independent and somewhat discrete regulatory mechanism of foraging behavior.Foraging behavior has also been extensively studied in invertebrate species such as the roundworm Caenorhabditis elegans (9) and fruit flies Drosophila melanogaster (10). Roundworm populations exhibit two naturally emerged foraging patterns: "solitary" worms disperse across the bacterial lawn, and "social" worms aggregate along the food edge and form clumps (9). This behavioral dimorphism is controlled by natural variations of the npr-1 (neuropeptide receptor resemblance) gene that encodes a receptor homologous to the receptor family of orexigenic neuropeptide Y in mammals (9). A comparable scenario has also been identified in larval fruit flies (10), with two distinct forms of foraging present in nature: "rover" and "sitter." On food sources, sitter but not rover reduces moving speed ...

Benzoyl chloride derivatization with liquid chromatography–mass spectrometry for targeted metabolomics of neurochemicals in biological samples

“…Of particular note was a nearly 5 fold increase of octopamine in starved flies relative to sated flies. Increased octopamine activity has been reported in flies upon starvation, and has been linked to foraging-like behaviors as the flies presumably try to locate food [60, 61]. The roles of other implicated metabolites are currently undergoing further investigation.…”

Internal states drive nutrient homeostasis by modulating exploration-exploitation trade-off

“…While octopamine has been shown to mediate the postmating increase in yeast feeding (Walker et al, 2015), it has been proposed that it does not contribute to homeostatic changes in feeding behavior (Yang et al, 2015). We therefore decided to show that our setup could be used to test possible neuromodulatory effects of octopamine on yeast foraging, using mutants for the gene encoding Tyramine β-hydroxylase (TβH), an enzyme required for the biosynthesis of octopamine in the whole animal.…”

Taotie neurons regulate appetite in Drosophila

“…In the periphery, both olfactory and gustatory inputs related to feeding are affected by hunger25455. In the brain, multiple neural transmitters (Serotonin, Dopamine and Octopamine) and neuropeptides (dNPF, sNPF, Drosulfakinin, Tachykinin, CCHamide-2 and Allatostatin A) participate in different, sometimes opposite, aspects of feeding response upon starvation131416172139434656. Thus, to improve our understanding of the mechanisms of hunger, it is important to distinguish whether a neural circuit associated with hunger-induced behaviour is the cause or the consequence of hunger sensation.…”

“…For example, in Drosophila , starvation enhances behavioural sensitivity to sugar partly via increased dopamine levels, and the activity of dopaminergic neurons is altered by the hungry state1617. Another neurotransmitter, octopamine, is crucial for starvation-induced hyperactivity, but not required for the regulation of energy intake during starvation56. Recent studies indicated that a subset of serotonergic neurons, the R4 neurons in ellipsoid body and four neurons in SEZ, participate in hunger sensation in Drosophila 216566.…”