Single-cell transcriptomics reveals that glial cells integrate homeostatic and circadian processes to drive sleep–wake cycles

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(2), P. 359 - 372

Published: Jan. 23, 2024

The sleep-wake cycle is determined by circadian and sleep homeostatic processes. However, the molecular impact of these processes their interaction in different brain cell populations are unknown. To fill this gap, we profiled single-cell transcriptome adult Drosophila brains across four times. We show type-specific transcriptomic changes, with glia displaying largest variation. Glia also among few types whose gene expression correlates both homeostat clock. drive level affect clock regulators glia, disrupting genes specifically impairs rebound after deprivation. These findings provide a comprehensive view effects on distinct an entire animal reveal as site two to determine dynamics.

Language: Английский

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Dietary L-Glu sensing by enteroendocrine cells adjusts food intake via modulating gut PYY/NPF secretion

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

Published: April 25, 2024

Abstract Amino acid availability is monitored by animals to adapt their nutritional environment. Beyond gustatory receptors and systemic amino sensors, enteroendocrine cells (EECs) are believed directly percept dietary acids secrete regulatory peptides. However, the cellular machinery underlying acid-sensing EECs how EEC-derived hormones modulate feeding behavior remain elusive. Here, developing tools specifically manipulate EECs, we find that Drosophila neuropeptide F (NPF) from mated female inhibits feeding, similar human PYY. Mechanistically, L-Glutamate acts through metabotropic glutamate receptor mGluR decelerate calcium oscillations in thereby causing reduced NPF secretion via dense-core vesicles. Furthermore, two dopaminergic enteric neurons expressing NPFR perceive relay an anorexigenic signal brain. Thus, our findings provide mechanistic insights into assess food quality identify a conserved mode of action explains gut NPF/PYY modulates intake.

Language: Английский

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Large-language models facilitate discovery of the molecular signatures regulating sleep and activity

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

Published: May 1, 2024

Abstract Sleep, locomotor and social activities are essential animal behaviors, but their reciprocal relationships underlying mechanisms remain poorly understood. Here, we elicit information from a cutting-edge large-language model (LLM), generative pre-trained transformer (GPT) 3.5, which interprets 10.2–13.8% of Drosophila genes known to regulate the 3 behaviors. We develop an instrument for simultaneous video tracking multiple moving objects, conduct genome-wide screen. have identified 758 fly that sleep activities, including mre11 regulates only in presence conspecifics, NELF-B regardless whether conspecifics present. Based on LLM-reasoning, educated signal web is modeled understanding potential between its components, presenting comprehensive molecular signatures control sleep, activities. This LLM-aided strategy may also be helpful addressing other complex scientific questions.

Language: Английский

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Whole-body connectome of a segmented annelid larva

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 17, 2024

Abstract Nervous systems coordinate effectors across the body during movements. We know little about cellular-level structure of synaptic circuits for such body-wide control. Here we describe whole-body connectome a segmented larva marine annelid Platynereis dumerilii . reconstructed and annotated over 9,000 neuronal non-neuronal cells in serial electron microscopy dataset. Differentiated were classified into 202 92 cell types. analyse modularity, multisensory integration, left-right intersegmental connectivity motor ciliated cells, glands, pigment muscles. identify several segment-specific types, demonstrating heteromery larval trunk. At same time, segmentally repeated types head, trunk segments pygidium suggest homology all segmental regions. also report descending ascending pathways, peptidergic multi-modal mechanosensory girdle. Our work provides basis understanding coordination an entire animal.

Language: Английский

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Sleep deprivation drives brain-wide changes in cholinergic presynapse abundance in Drosophila melanogaster

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(13)

Published: March 18, 2024

Sleep is an evolutionarily conserved state that supports brain functions, including synaptic plasticity, in species across the animal kingdom. Here, we examine neuroanatomical and cell-type distribution of presynaptic scaling fly after sleep loss. We previously found loss drives accumulation active zone scaffolding protein Bruchpilot (BRP) within cholinergic Kenyon cells Drosophila melanogaster mushroom body (MB), but not other classes MB neurons. To test whether similar cell type–specific trends plasticity occur broadly brain, used a flp-based genetic reporter to label BRP cholinergic, dopaminergic, GABAergic, or glutamatergic then collected whole-brain confocal image stacks intensity systematically quantify BRP, marker presynapse abundance, 37 neuropil regions central brain. Our results indicate loss, either by overnight (12-h) mechanical stimulation chronic disruption insomniac mutants, elevates synapse abundance while neurons produce neurotransmitters undergoes weaker, if any, changes. Extending deprivation 24 h brain-wide upscaling glutamatergic, other, synapses. Finally, male–male social pairings induce increased excitatory synapses despite male–female eliciting more waking activity, suggesting experience-specific plasticity. Within neurotransmitter class context, changes are domains, indicating rules may apply during acute need alter excitatory–inhibitory balance

Language: Английский

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