Aminergic and peptidergic modulation of Insulin-Producing Cells in Drosophila DOI Open Access
Martina Held, Rituja S Bisen, Meet Zandawala

et al.

Published: Sept. 10, 2024

Insulin plays a critical role in maintaining metabolic homeostasis. Since demands are highly dynamic, insulin release needs to be constantly adjusted. These adjustments mediated by different pathways, most prominently the blood glucose level, but also feedforward signals from motor circuits and neuromodulatory systems. Here, we analyze how inputs control activity of main source Drosophila – population Insulin-Producing Cells (IPCs) located brain. IPCs functionally analogous mammalian pancreatic beta cells, their location makes them accessible for vivo recordings intact animals. We characterized functional using single-nucleus RNA sequencing analysis, anatomical receptor expression mapping, connectomics, an optogenetics-based ‘in-trinsic pharmacology’ approach. Our results show that IPC expresses variety receptors neuromodulators classical neurotransmitters. Interestingly, exhibit heterogeneous profiles, suggesting can modulated differentially. This is supported electrophysiological IPCs, which performed while activating populations modulatory neurons. analysis revealed some have effects on activity, such they inhibit one subset exciting another. Monitoring calcium across uncovered these responses occur simultaneously. Certain shifted towards excited state, others it inhibition. Taken together, provide comprehensive, multi-level neuromodulation insulinergic system .

Language: Английский

A neuronal ensemble encoding adaptive choice during sensory conflict in Drosophila DOI Creative Commons
Preeti Sareen, Li Yan McCurdy, Michael N. Nitabach

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: July 5, 2021

Abstract Feeding decisions are fundamental to survival, and decision making is often disrupted in disease. Here, we show that neural activity a small population of neurons projecting the fan-shaped body higher-order central brain region Drosophila represents food choice during sensory conflict. We found deprived flies made tradeoffs between appetitive aversive values food. identified an upstream neuropeptidergic dopaminergic network relays internal state other decision-relevant information specific subset neurons. These were strongly inhibited by taste rejected choice, suggesting they encode behavioral choice. Our findings reveal responses choices determined not only quality, but also previous experience (including outcome) hunger state, which integrated before relay downstream motor circuits for implementation.

Language: Английский

Citations

42

Cholecystokinin/sulfakinin peptide signaling: conserved roles at the intersection between feeding, mating and aggression DOI Creative Commons
Dick R. Nässel, Shun‐Fan Wu

Cellular and Molecular Life Sciences, Journal Year: 2022, Volume and Issue: 79(3)

Published: March 1, 2022

Neuropeptides are the most diverse messenger molecules in metazoans and involved regulation of daily physiology a wide array behaviors. Some neuropeptides their cognate receptors structurally functionally well conserved over evolution bilaterian animals. Among these peptides related to gastrin cholecystokinin (CCK). In mammals, CCK is produced by intestinal endocrine cells brain neurons, regulates gall bladder contractions, pancreatic enzyme secretion, gut functions, satiety food intake. Additionally, plays important roles neuromodulation several circuits that regulate reward, anxiety, aggression sexual behavior. invertebrates, CCK-type (sulfakinins, SKs) are, with few exceptions, neurons only. Common among invertebrates SKs mediate ingestion variety mechanisms. Also secretion digestive enzymes has been reported. Studies genetically tractable fly Drosophila have advanced our understanding SK signaling mechanisms feeding, but also gustatory sensitivity, locomotor activity, reproductive A set eight SK-expressing competing males, they integrate internal state external stimuli diminish sex drive increase aggression. The same sugar gustation, induce reduce feeding. Although functional CCK/SK appear between available data suggest underlying differ.

Language: Английский

Citations

35

Synaptic connectome of theDrosophilacircadian clock DOI Creative Commons
Nils Reinhard,

Ayumi Fukuda,

Giulia Manoli

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 13, 2023

The circadian clock and its output pathways play a pivotal role in optimizing daily processes. To obtain novel insights into how diverse rhythmic physiology behaviors are orchestrated, we have generated the first comprehensive connectivity map of an animal using Drosophila FlyWire brain connectome. Intriguingly, identified additional dorsal neurons, thus showing that network contains ∼240 instead 150 neurons. We also revealed extensive contralateral synaptic within discovered indirect light input to Interestingly, observed sparse monosynaptic between neurons down-stream higher-order centers neurosecretory cells known regulate behavior physiology. Therefore, integrated single-cell transcriptomics receptor mapping decipher putative paracrine peptidergic signaling by Our analyses neuropeptides expressed suggest significantly enriches interconnectivity network.

Language: Английский

Citations

22

Anti-diuretic hormone ITP signals via a guanylate cyclase receptor to modulate systemic homeostasis in Drosophila DOI Open Access
Jayati Gera, Marishia Agard,

Hannah Nave

et al.

Published: May 7, 2024

Insects have evolved a variety of neurohormones that enable them to maintain their nutrient and osmotic homeostasis. While the identities functions various insect metabolic diuretic hormones been well-established, characterization an anti-diuretic signaling system is conserved across most insects still lacking. To address this, here we characterized ion transport peptide (ITP) in Drosophila . The ITP gene encodes five transcript variants which generate three different isoforms: amidated (ITPa) two ITP-like (ITPL1 ITPL2) isoforms. Using combination anatomical mapping single-cell transcriptome analyses, comprehensively expression all isoforms nervous peripheral tissues. Our analyses reveal widespread Moreover, show ITPa released during dehydration recombinant inhibits peptide-induced renal tubule secretion ex vivo , thus confirming its role as hormone. phylogenetic-driven approach assay, identified functionally Gyc76C, membrane guanylate cyclase, elusive receptor. Thus, knockdown Gyc76C tubules abolishes inhibitory effect on hormone secretion. Extensive reveals it highly expressed larval adult tissues associated with osmoregulation (renal rectum) homeostasis (fat body). Consistent this expression, impacts tolerance ionic stresses, whereas specifically fat body feeding, behaviors. We also complement receptor experiments overexpression neurons. Interestingly, ITPa-Gyc76C pathways deciphered are reminiscent atrial natriuretic mammals. Lastly, utilized connectomics transcriptomics identify synaptic paracrine upstream downstream ITP-expressing Taken together, our systematic establishes tractable decipher how small set neurons integrates diverse inputs orchestrate systemic

Language: Английский

Citations

6

Aminergic and peptidergic modulation of Insulin-Producing Cells in Drosophila DOI Open Access
Martina Held, Rituja S Bisen, Meet Zandawala

et al.

Published: Sept. 10, 2024

Insulin plays a critical role in maintaining metabolic homeostasis. Since demands are highly dynamic, insulin release needs to be constantly adjusted. These adjustments mediated by different pathways, most prominently the blood glucose level, but also feedforward signals from motor circuits and neuromodulatory systems. Here, we analyze how inputs control activity of main source Drosophila – population Insulin-Producing Cells (IPCs) located brain. IPCs functionally analogous mammalian pancreatic beta cells, their location makes them accessible for vivo recordings intact animals. We characterized functional using single-nucleus RNA sequencing analysis, anatomical receptor expression mapping, connectomics, an optogenetics-based ‘in-trinsic pharmacology’ approach. Our results show that IPC expresses variety receptors neuromodulators classical neurotransmitters. Interestingly, exhibit heterogeneous profiles, suggesting can modulated differentially. This is supported electrophysiological IPCs, which performed while activating populations modulatory neurons. analysis revealed some have effects on activity, such they inhibit one subset exciting another. Monitoring calcium across uncovered these responses occur simultaneously. Certain shifted towards excited state, others it inhibition. Taken together, provide comprehensive, multi-level neuromodulation insulinergic system .

Language: Английский

Citations

6