Deterministic Genetic Barcoding for Multiplexed Behavioral and Single-Cell Transcriptomic Studies DOI Creative Commons

Jorge Blanco Mendana,

Margaret Donovan, Lindsey Gengelbach O'Brien

et al.

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

Published: April 1, 2023

Abstract Advances in single-cell sequencing technologies have provided novel insights into the dynamics of gene expression throughout development, been used to characterize somatic variation and heterogeneity within tissues, are currently enabling construction transcriptomic cell atlases. However, despite these remarkable advances, linking anatomical information data positively identifying types that correspond clusters sets remains a challenge. We describe straightforward genetic barcoding approach takes advantage powerful tools available Drosophila allow vivo tagging defined populations. This method, called Ta rgeted G enetically- E ncoded M ultiplexing (TaG-EM), involves inserting DNA barcode just upstream polyadenylation site Gal4-inducible UAS-GFP construct so sequence can be read out during sequencing, labeling population interest. By creating many such independently barcoded fly strains, TaG-EM will enable number potential applications improve quality content including positive identification atlas projects, multiplet droplets, experimental timepoints, conditions, replicates. Furthermore, we demonstrate barcodes from lines using next-generation facilitate population-scale behavioral measurements. Thus, has large-scale screens addition improving ability reliably annotate data, expanding scope, robustness experiments.

Language: Английский

Brainstem neuropeptidergic neurons link a neurohumoral axis to satiation DOI
Srikanta Chowdhury,

Nachiket G. Kamatkar,

Wendy Xueyi Wang

et al.

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

3
Understanding the effects of serotonin in the brain through its role in the gastrointestinal tract DOI Open Access
James M. Shine, Claire O’Callaghan, Ishan C. Walpola

et al.

Brain, Journal Year: 2022, Volume and Issue: 145(9), P. 2967 - 2981

Published: July 23, 2022

Abstract The neuromodulatory arousal system imbues the nervous with flexibility and robustness required to facilitate adaptive behaviour. While there are well understood mechanisms linking dopamine, noradrenaline acetylcholine distinct behavioural states, similar conclusions have not been as readily available for serotonin. Fascinatingly, despite clear links between serotonergic function cognitive capacities diverse reward processing, exploration, psychedelic experience, over 95% of serotonin in body is released gastrointestinal tract, where it controls digestive muscle contractions (peristalsis). Here, we argue that framing neural a rostral extension dissolves much mystery associated central system. Specifically, outline activity mimics effects digestion/satiety circuit mediated by hypothalamic control descending nuclei brainstem. We review commonalities differences these two circuits, focus on heterogeneous expression different classes receptors brain. Much way serotonin-induced peristalsis facilitates work digestion, influences cognition can be reframed performing cognition. Extending this analogy, allows brain arbitrate modes tone: low automaticity, whereas higher helps identify flexible solutions problems, particularly if when initial responses fail. This perspective sheds light otherwise disparate serotonin, also understand why such pervasive pathology symptoms psychiatric disorders.

Language: Английский

Citations

44
Nutritional state-dependent modulation of insulin-producing cells in Drosophila DOI Creative Commons
Rituja S Bisen,

Fathima Mukthar Iqbal,

Federico Cascino-Milani

et al.

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

Published: Jan. 29, 2025

Insulin plays a key role in metabolic homeostasis. Drosophila insulin-producing cells (IPCs) are functional analogues of mammalian pancreatic beta and release insulin directly into circulation. To investigate the vivo dynamics IPC activity, we quantified effects nutritional internal state changes on IPCs using electrophysiological recordings. We found that strongly modulates activity. activity decreased with increasing periods starvation. Refeeding flies glucose or fructose, two nutritive sugars, significantly increased whereas non-nutritive sugars had no effect. In contrast to feeding, perfusion did not affect This was reminiscent incretin effect, where ingestion drives higher than intravenous application. Contrary IPCs, Diuretic hormone 44-expressing neurons pars intercerebralis (DH44 PI Ns) responded perfusion. Functional connectivity experiments demonstrated these DH44 Ns do while other DH44Ns inhibit them. Hence, populations autonomously systemically sugar-sensing work parallel maintain Accordingly, activating small, satiety-like effect food-searching behavior reduced starvation-induced hyperactivity, hyperactivity. Taken together, demonstrate an integral part modulatory network orchestrates homeostasis adaptive response shifts state.

Language: Английский

Citations

1
Selective integration of diverse taste inputs within a single taste modality DOI Creative Commons

Julia U. Deere,

Arvin A Sarkissian,

Meifeng Yang

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Jan. 24, 2023

A fundamental question in sensory processing is how different channels of input are processed to regulate behavior. Different may converge onto common downstream pathways drive the same behaviors, or they activate separate distinct behaviors. We investigated this Drosophila bitter taste system, which contains diverse bitter-sensing cells residing organs. First, we optogenetically activated subsets neurons within each organ. These elicited broad and highly overlapping behavioral effects, suggesting that pathways, but also observed differences argue for biased convergence. Consistent with these results, transsynaptic tracing revealed organs connect connectivity. one type neuron projects higher brain. integrate from multiple specific taste-related then traced circuits, providing first glimpse into Together, results reveal inputs selectively integrated early circuit, enabling pooling information, while circuit diverges have roles.

Language: Английский

Citations

17
Behavioral state-dependent modulation of insulin-producing cells in Drosophila DOI Creative Commons
Sander Liessem, Martina Held, Rituja S Bisen

et al.

Current Biology, Journal Year: 2022, Volume and Issue: 33(3), P. 449 - 463.e5

Published: Dec. 28, 2022

Language: Английский

Citations

28
Mating activates neuroendocrine pathways signaling hunger in Drosophila females DOI Creative Commons
Meghan Laturney, Gabriella R Sterne, Kristin Scott

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: May 15, 2023

Mated females reallocate resources to offspring production, causing changes nutritional requirements and challenges energy homeostasis. Although observed across species, the neural endocrine mechanisms that regulate needs of mated are not well understood. Here, we find

Language: Английский

Citations

15
Unraveling the serotonin saga: from discovery to weight regulation and beyond - a comprehensive scientific review DOI Creative Commons
Kristie Conde,

Shuzheng Fang,

Yong Xu

et al.

Cell & Bioscience, Journal Year: 2023, Volume and Issue: 13(1)

Published: Aug. 7, 2023

The prevalence of obesity is rapidly increasing worldwide, while the development effective therapies lags behind. Although new therapeutic targets to alleviate are identified every day, and drug efficacy improving, adverse side effects increased health risks remain serious issues facing weight-loss industry. Serotonin, also known as 5-HT, has been extensively studied in relation appetite reduction weight loss. As a result, dozens upstream downstream neural 5-HT have identified, revealing multitude circuits involved mediating anorexigenic effect 5-HT. Despite rise fall several therapeutics recent decades, future target for therapy looks promising. This review focuses on history serotonin, state current central serotonin research, previous serotonergic therapies, treating individuals with obesity.

Language: Английский

Citations

13
A nutrient responsive lipase mediates gut-brain communication to regulate insulin secretion in Drosophila DOI Creative Commons

Alka Singh,

Kandahalli Venkataranganayaka Abhilasha,

Kathya R. Acharya

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 23, 2024

Abstract Pancreatic β cells secrete insulin in response to glucose elevation maintain homeostasis. A complex network of inter-organ communication operates modulate secretion and regulate levels after a meal. Lipids obtained from diet or generated intracellularly are known amplify glucose-stimulated secretion, however, the underlying mechanisms not completely understood. Here, we show that Drosophila secretory lipase, Vaha (CG8093), is synthesized midgut moves brain where it concentrates insulin-producing process requiring Lipid Transfer Particle, lipoprotein originating fat body. In dietary fat, stimulates insulin-like peptide release (ILP), deficiency results reduced circulatory ILP diabetic features including hyperglycemia hyperlipidemia. Our findings suggest functions as diacylglycerol lipase physiologically, by being molecular link between lipid amplified gut-brain axis.

Language: Английский

Citations

4
Nutritional state-dependent modulation of Insulin-Producing Cells in Drosophila DOI Open Access
Rituja S Bisen,

Fathima Mukthar Iqbal,

Federico Cascino-Milani

et al.

Published: July 2, 2024

Insulin plays a key role in regulating metabolic homeostasis across vertebrate and invertebrate species. Drosophila Insulin-Producing Cells (IPCs) are functional analogues to mammalian pancreatic beta cells release insulin directly into circulation. IPC activity is modulated by nutrient availability, circadian time, the behavioral state of animals. To investigate vivo dynamics context homeostasis, we quantified effects nutritional internal changes on IPCs using electrophysiological recordings. We found that strongly modulates activity. were less active starved flies than fed flies. Refeeding with glucose significantly increased activity, suggesting regulated hemolymph sugar levels. In contrast feeding, perfusion had no effect This was reminiscent incretin effect, which ingestion drives higher intravenous application. Contrary IPCs, Diuretic hormone 44-expressing neurons pars intercerebralis (DH44 PI Ns), anatomically similar their during perfusion. Functional connectivity experiments based optogenetic activation demonstrated glucose-sensing DH44 Ns do not affect while other DH44Ns inhibit IPCs. suggests populations autonomously systemically working parallel maintain homeostasis. Ultimately, animal behavior. For example, hungry increase locomotor search food support this idea, activating small, satiety-like flies, resulting reduced walking whereas Taken together, show an integral part sophisticated modulatory network orchestrates adaptive behavior response shifts state.

Language: Английский

Citations

4
Serotonergic modulation of swallowing in a complete fly vagus nerve connectome DOI Creative Commons
Andreas Schoofs, Anton Miroschnikow, Philipp Schlegel

et al.

Current Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

Citations

4