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

et al.

eLife, Journal Year: 2024, Volume and Issue: unknown

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 'intrinsic 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 Drosophila.

Language: Английский

Activity Monitoring for Analysis of Sleep inDrosophila melanogaster DOI
Divya Sitaraman, Christopher G. Vecsey,

Casey Koochagian

et al.

Cold Spring Harbor Protocols, Journal Year: 2024, Volume and Issue: 2024(11), P. pdb.top108095 - pdb.top108095

Published: Feb. 9, 2024

Sleep is important for survival, and the need sleep conserved across species. In past two decades, fruit fly

Language: Английский

Citations

7
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
Nutrients and pheromones promote insulin release to inhibit courtship drive DOI Creative Commons
Liwei Zhang, Xuan Guo,

Wei Zhang

et al.

Science Advances, Journal Year: 2022, Volume and Issue: 8(10)

Published: March 9, 2022

Food and reproduction are the fundamental needs for all animals. However, neural mechanisms that orchestrate nutrient intake sexual behaviors not well understood. Here, we find sugar feeding immediately suppresses drive of male Drosophila , a regulation mediated by insulin acts on receptors courtship-promoting P1 neurons. The same pathway was co-opted anaphrodisiac pheromones to suppress hyperactivity suboptimal mates. Activated repulsive pheromones, male-specific PPK23 neurons leg tarsus release crustacean cardioactive peptide (CCAP) CCAP receptor insulin-producing cells in brain trigger release, which then inhibits Our results reveal how flies avoid promiscuity balancing weight between aphrodisiac inputs from multiple peripheral sensory pathways nutritional states. Such enables animals make an appropriate mating decision under fluctuating conditions.

Language: Английский

Citations

26
Chronic sleep loss sensitizes Drosophila melanogaster to nitrogen stress DOI Creative Commons
Joseph L. Bedont,

Anna Kolesnik,

Pavel Pivarshev

et al.

Current Biology, Journal Year: 2023, Volume and Issue: 33(8), P. 1613 - 1623.e5

Published: March 24, 2023

Chronic sleep loss profoundly impacts metabolic health and shortens lifespan, but studies of the mechanisms involved have focused largely on acute deprivation.

Language: Английский

Citations

16
Polyphasic circadian neural circuits drive differential activities in multiple downstream rhythmic centers DOI Creative Commons
Xitong Liang, Timothy E. Holy, Paul H. Taghert

et al.

Current Biology, Journal Year: 2023, Volume and Issue: 33(2), P. 351 - 363.e3

Published: Jan. 1, 2023

Language: Английский

Citations

12
Dietary restriction fails to extend lifespan of Drosophila model of Werner syndrome DOI Creative Commons

Eileen Sember,

Ranga Chennakesavula,

Breanna Beard

et al.

G3 Genes Genomes Genetics, Journal Year: 2024, Volume and Issue: 14(5)

Published: March 16, 2024

Werner syndrome (WS) is a rare genetic disease in humans, caused by mutations the WRN gene that encodes protein containing helicase and exonuclease domains. WS characterized symptoms of accelerated aging multiple tissues organs, involving increased risk cancer, heart failure, metabolic dysfunction. These conditions ultimately lead to premature mortality patients with WS. In this study, using null mutant flies (WRNexoΔ) for WRNexo (CG7670), homologous domain we examined how diets affect lifespan, stress resistance, sleep/wake patterns Drosophila model We observed dietary restriction (DR), one most robust nongenetic interventions extend lifespan animal models, failed WRNexoΔ even had detrimental effect females. Interestingly, mean was not reduced on protein-rich diet compared wild-type (WT) flies. Compared WT control flies, also exhibited altered responses DR their resistance starvation oxidative stress, as well changes patterns. findings show necessary mediating effects suggest plays an important role metabolism addition its primary DNA-repair genome stability.

Language: Английский

Citations

4
Aminergic and peptidergic modulation of insulin-producing cells in Drosophila DOI Creative Commons
Martina Held, Rituja S Bisen, Meet Zandawala

et al.

eLife, Journal Year: 2025, Volume and Issue: 13

Published: March 10, 2025

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 ‘intrinsic 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

0
Measuring metabolic rate in single flies during sleep and waking states via indirect calorimetry DOI Creative Commons
Elizabeth Brown,

Jaco Klok,

Alex C. Keene

et al.

Journal of Neuroscience Methods, Journal Year: 2022, Volume and Issue: 376, P. 109606 - 109606

Published: April 26, 2022

Drosophila melanogaster is a leading genetic model for studying the neural regulation of sleep. Sleep associated with changes in behavior and physiological state that are largely conserved across species. The investigation sleep flies has predominantly focused on behavioral readouts because measurements, including brain activity metabolic rate, less accessible. We have previously used stop-flow indirect calorimetry to measure whole body rate single shown flies, like mammals, reduced during sleep.Here, we describe modified version this system allows efficient highly sensitive acquisition CO2 output from flies.In system, show sleep-dependent diminished aging supporting notion quality as age. also modification simultaneous O2 levels, providing respiratory quotient quantifies how stores utilized. find identified an all-sugar diet suggestive lipogenesis, where dietary sugar provided being converted fat.Taken together, measurement via not only provides readout depth, but insight nutrient utilization, broad applications studies flies.

Language: Английский

Citations

16
Aminergic and peptidergic modulation of Insulin-Producing Cells inDrosophila DOI Open Access
Martina Held, Rituja S Bisen, Meet Zandawala

et al.

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

Published: Sept. 14, 2023

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 ‘intrinsic 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

8
Metabolic control of daily locomotor activity mediated by tachykinin in Drosophila DOI Creative Commons
Sang Hyuk Lee, Eunjoo Cho, Sung‐Eun Yoon

et al.

Communications Biology, Journal Year: 2021, Volume and Issue: 4(1)

Published: June 7, 2021

Metabolism influences locomotor behaviors, but the understanding of neural curcuit control for that is limited. Under standard light-dark cycles, Drosophila exhibits bimodal morning (M) and evening (E) activities are controlled by clock neurons. Here, we showed a high-nutrient diet progressively extended M activity not E activity. tachykinin (DTk) Tachykinin-like receptor at 86C (TkR86C)-mediated signaling was required extension DTk neurons were anatomically functionally connected to posterior dorsal neuron 1s (DN1ps) in neuronal network. The activation reduced intracellular Ca2+ levels DN1ps suggesting an inhibitory connection. contacts between increased gradually over time flies fed high-sucrose diet, consistent with behavior. have been implicated integrating environmental sensory inputs (e.g., light temperature) daily This study revealed also coordinated nutrient information through shape

Language: Английский

Citations

19