Transcriptome Analysis of NPFR Neurons Reveals a Connection Between Proteome Diversity and Social Behavior

Ryvkin, Julia; Bentzur, Assa; Shmueli, Anat; Tannenbaum, Miriam; Shallom, Omri; Dokarker, Shiran; Benichou, Jennifer I. C.; Levi, Mali; Shohat-Ophir, Galit

doi:10.3389/fnbeh.2021.628662

Cited by 7 publications

(14 citation statements)

References 111 publications

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“…14a ). This is consistent with a recent RNA-seq analysis showing that NPFR is indeed expressed in the IPCs 53 . We further investigated potential control Dilps mRNA expression by NPFR in the IPCs.…”

Section: Resultssupporting

confidence: 93%

The sugar-responsive enteroendocrine neuropeptide F regulates lipid metabolism through glucagon-like and insulin-like hormones in Drosophila melanogaster

et al. 2021

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The enteroendocrine cell (EEC)-derived incretins play a pivotal role in regulating the secretion of glucagon and insulins in mammals. Although glucagon-like and insulin-like hormones have been found across animal phyla, incretin-like EEC-derived hormones have not yet been characterised in invertebrates. Here, we show that the midgut-derived hormone, neuropeptide F (NPF), acts as the sugar-responsive, incretin-like hormone in the fruit fly, Drosophila melanogaster. Secreted NPF is received by NPF receptor in the corpora cardiaca and in insulin-producing cells. NPF-NPFR signalling resulted in the suppression of the glucagon-like hormone production and the enhancement of the insulin-like peptide secretion, eventually promoting lipid anabolism. Similar to the loss of incretin function in mammals, loss of midgut NPF led to significant metabolic dysfunction, accompanied by lipodystrophy, hyperphagia, and hypoglycaemia. These results suggest that enteroendocrine hormones regulate sugar-dependent metabolism through glucagon-like and insulin-like hormones not only in mammals but also in insects.

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Section: Resultssupporting

confidence: 93%

The sugar-responsive enteroendocrine neuropeptide F regulates lipid metabolism through glucagon-like and insulin-like hormones in Drosophila melanogaster

et al. 2021

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“…Another courtship-related gene identified in our dataset was Ubiquitin-conjugating enzyme7 (Ubc7), which was down-regulated in response to rejection (Fig. 2E,F,H) 60,89 . Focusing on DEGs specific for the rejected cohort, we identified 15 genes (Fig.…”

Section: Resultsmentioning

confidence: 94%

“…To assess whether activation of these neurons also mediates other behavioral phenotypes observed in rejected males, we assayed the behavior of NPFR>csChrimson flies during optogenetic activation in an open field exploration arena (FlyBowl) in which flies can move and interact in two dimensions. The system is coupled with a tracking and machine learning algorithms capable of automatically quantifying various behavioral parameters 60,119 . Intriguingly, we observed no difference in the behavior of experimental flies compared to both genetic controls (NPFRG4\+, UAS-csChrimson\+) (Fig.…”

Section: Disinhibition Of Npfr Neurons Increases Sensitivity To Starv...mentioning

confidence: 99%

“…The homologs for NPY and CRF in Drosophila are Neuropeptide F (NPF) and Diuretic hormone 44 (Dh44), respectively [56][57][58] . Their effects on behavior are similar to those of mammals: the NPF and the NPF receptor (NPFR) system in flies mediates the response to reward and rewardseeking behavior, feeding behavior, suppresses responses to aversive stimuli such as harsh physical environments, decreases aggressive behaviors, and mediates courtship behavior 40,56,[59][60][61][62][63][64][65][66][67][68] . Like CRF neurons, the Dh44 signaling pathway facilitates aggressive behavior in males, although whether Dh44 neurons mediate social stress response is still unknown 69 .…”

Section: Introductionmentioning

confidence: 99%

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Sexual deprivation induces a CRF independent stress response and decreases resistance to stressors inDrosophilavia a subpopulation of Neuropeptide F receptor-expressing neurons

Ryvkin

Shmueli

Levi

et al. 2022

Preprint

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Living in a changing environment composed of other behaving animals entails both opportunities and challenges to obtain resources and mating partners. Actions that promote survival and reproduction are reinforced by the brain reward systems, whereas coping with the challenges associated with obtaining these rewards are mediated by stress response pathways. The activation of the latter can impair health and shorten lifespan. Although similar responses to social opportunity and challenge exist across the animal kingdom, little is known about the mechanisms that process reward and stress under different social conditions. Here, we studied the interplay between deprivation of sexual reward and stress response in Drosophila melanogaster and discovered that repeated failures to obtain sexual reward induces a frustration-like state that is characterized by increased arousal, persistent sexual motivation, and impaired ability to cope with starvation and oxidative stressors. We show that this increased arousal and sensitivity to starvation is mediated by disinhibition of neurons that express receptors for the fly homologue of neuropeptide Y (neuropeptide F, NPF). We furthermore demonstrate the existence of an anatomical overlap between stress and reward systems in the fly brain in the form of neurons that co-express receptors for NPF (NPFR) and the corticotropin-releasing factor (CRF)-like homologue Diuretic hormone 44 (Dh44), and that deprivation of sexual reward leads to translocation of forkhead box-subgroup O (FoxO) to the cytoplasm in these neurons. Nevertheless, the activity of Dh44 neurons alone does not mediate sensitivity to starvation and aroused behavior following sexual deprivation, instead, these responses are mediated by disinhibition of ~12-16 NPFR-expressing neurons via a dynamin-independent synaptic signaling mechanism, suggesting the existence of a NPFR mediated stress pathway which is Dh44-independent. This paves the path for using simple model organisms to dissect mechanisms behind anticipation of reward, and more specifically, to determine what happens when expectations to obtain natural and drug rewards are not met.

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“…However, at the transcriptomic level, differences between Crz and NPFR1 neurons have been observed in regard to their RNA editing profiles [ 70 ]. Intriguingly, a recent study demonstrated that reduced RNA editing via knockdown of ADAR (adenosine deaminase acting on RNA) in NPFR neurons enhanced male–male social interactions, whereas ADAR knockdown in Crz neurons had moderate effects [ 71 ].…”

Section: Role Of Crz Neurons In Ethanol-related Behaviorsmentioning

confidence: 99%

Drosophila Corazonin Neurons as a Hub for Regulating Growth, Stress Responses, Ethanol-Related Behaviors, Copulation Persistence and Sexually Dimorphic Reward Pathways

Khan

Tondravi

Oliver

et al. 2021

JDB

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The neuronal mechanisms by which complex behaviors are coordinated and timed often involve neuropeptidergic regulation of stress and reward pathways. Recent studies of the neuropeptide Corazonin (Crz), a homolog of the mammalian Gonadotrophin Releasing Hormone (GnRH), have suggested its crucial role in the regulation of growth, internal states and behavioral decision making. We focus this review on Crz neurons with the goal to (1) highlight the diverse roles of Crz neuron function, including mechanisms that may be independent of the Crz peptide, (2) emphasize current gaps in knowledge about Crz neuron functions, and (3) propose exciting ideas of novel research directions involving the use of Crz neurons. We describe the different developmental fates of distinct subsets of Crz neurons, including recent findings elucidating the molecular regulation of apoptosis. Crz regulates systemic growth, food intake, stress responses and homeostasis by interacting with the short Neuropeptide F (sNPF) and the steroid hormone ecdysone. Additionally, activation of Crz neurons is shown to be pleasurable by interacting with the Neuropeptide F (NPF) and regulates reward processes such as ejaculation and ethanol-related behaviors in a sexually dimorphic manner. Crz neurons are proposed to be a motivational switch regulating copulation duration using a CaMKII-dependent mechanism described as the first neuronal interval timer lasting longer than a few seconds. Lastly, we propose ideas to use Crz neuron-induced ejaculation to study the effects of fictive mating and sex addiction in flies, as well as to elucidate dimorphic molecular mechanisms underlying reward behaviors and feeding disorders.

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Transcriptome Analysis of NPFR Neurons Reveals a Connection Between Proteome Diversity and Social Behavior

Cited by 7 publications

References 111 publications

The sugar-responsive enteroendocrine neuropeptide F regulates lipid metabolism through glucagon-like and insulin-like hormones in Drosophila melanogaster

The sugar-responsive enteroendocrine neuropeptide F regulates lipid metabolism through glucagon-like and insulin-like hormones in Drosophila melanogaster

Sexual deprivation induces a CRF independent stress response and decreases resistance to stressors inDrosophilavia a subpopulation of Neuropeptide F receptor-expressing neurons

Drosophila Corazonin Neurons as a Hub for Regulating Growth, Stress Responses, Ethanol-Related Behaviors, Copulation Persistence and Sexually Dimorphic Reward Pathways

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