A Rare Mutation of β1-Adrenergic Receptor Affects Sleep/Wake Behaviors

Neuron, Journal Year: 2019, Volume and Issue: 103(6), P. 1044 - 1055.e7

Published: Aug. 28, 2019

Language: Английский

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D-Serine made by serine racemase in Drosophila intestine plays a physiological role in sleep

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: May 7, 2019

Abstract Natural D-serine (D-Ser) has been detected in animals more than two decades ago, but little is known about the physiological functions of D-Ser. Here we reveal sleep regulation by endogenous Sleep was decreased mutants defective D-Ser synthesis or its receptor N-methyl-D-aspartic 1 (NMDAR1), increased degradation. not L-Ser rescued phenotype lacking serine racemase (SR), key enzyme for synthesis. Pharmacological and triple gene knockout experiments indicate that upstream NMDAR1. Expression SR both nervous system intestines. Strikingly, reintroduction into specific intestinal epithelial cells sr mutants. Our results have established a novel function surprising role cells.

Language: Английский

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Sleep-Active Neurons: Conserved Motors of Sleep

Genetics, Journal Year: 2018, Volume and Issue: 208(4), P. 1279 - 1289

Published: April 1, 2018

Sleep is crucial for survival and well-being. This behavioral physiological state has been studied in all major genetically accessible model animals, including rodents, fish, flies, worms. Genetic optogenetic studies have identified several neurons that control sleep, making it now possible to compare circuit mechanisms across species. The "motor" of sleep animal species formed by depolarize at the onset actively induce this directly inhibiting wakefulness. These sleep-inducing are themselves controlled inhibitory or activating upstream pathways, which act as "drivers" motor: arousal inhibits "sleep-active" whereas various sleep-promoting "tiredness" pathways converge onto sleep-active them. review provides first overview animals. occurrence their regulation both vertebrate invertebrate suggests these general ancient components evolved early history nervous systems.

Language: Английский

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Drosophila insulin-like peptide 2 mediates dietary regulation of sleep intensity

PLoS Genetics, Journal Year: 2020, Volume and Issue: 16(3), P. e1008270 - e1008270

Published: March 11, 2020

Sleep is a nearly universal behavior that regulated by diverse environmental stimuli and physiological states. A defining feature of sleep homeostatic rebound following deprivation, where animals compensate for lost increasing duration and/or depth. The fruit fly, Drosophila melanogaster, exhibits robust recovery deprivation represents powerful model to study neural circuits regulating homeostasis. Numerous neuronal populations have been identified in modulating homeostasis as well depth, raising the possibility quality dependent on or processes induce deprivation. Here, we find unlike most pharmacological manipulations commonly used restrict sleep, starvation potently induces loss without subsequent Both sucrose-only diet result increased suggesting dietary protein essential normal depth Finally, insulin like peptide 2 (Dilp2) acutely required starvation-induced changes sleep. Flies lacking Dilp2 exhibit compensatory promotes resiliency loss. Together, these findings reveal innate resilience identify distinct mechanisms underlie

Language: Английский

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A neural circuit for flexible control of persistent behavioral states

eLife, Journal Year: 2021, Volume and Issue: 10

Published: Nov. 18, 2021

To adapt to their environments, animals must generate behaviors that are closely aligned a rapidly changing sensory world. However, behavioral states such as foraging or courtship typically persist over long time scales ensure proper execution. It remains unclear how neural circuits persistent while maintaining the flexibility select among alternative when context changes. Here, we elucidate functional architecture of circuit controlling choice between roaming and dwelling states, which underlie exploration exploitation during in C. elegans. By imaging ensemble-level activity freely moving animals, identify stereotyped changes corresponding each state. Combining circuit-wide with genetic analysis, find mutual inhibition two antagonistic neuromodulatory systems underlies persistence exclusivity patterns observed Through machine learning analysis perturbations, processing neuron can transmit information about food odors both bias animal towards different contexts, giving rise context-appropriate state transitions. Our findings reveal potentially general enables flexible, sensory-driven control states.

Language: Английский

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A connectome of theDrosophilacentral complex reveals network motifs suitable for flexible navigation and context-dependent action selection

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2020, Volume and Issue: unknown

Published: Dec. 9, 2020

ABSTRACT Flexible behaviors over long timescales are thought to engage recurrent neural networks in deep brain regions, which experimentally challenging study. In insects, circuit dynamics a region called the central complex (CX) enable directed locomotion, sleep, and context- experience-dependent spatial navigation. We describe first complete electron-microscopy-based connectome of Drosophila CX, including all its neurons circuits at synaptic resolution. identified new CX neuron types, novel sensory motor pathways, network motifs that likely extract fly’s head-direction, maintain it with attractor dynamics, combine other sensorimotor information perform vector-based navigational computations. also numerous pathways may facilitate selection CX-driven behavioral patterns by context internal state. The provides comprehensive blueprint necessary for detailed understanding underlying flexible navigation, state-dependent action selection.

Language: Английский

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Widespread posttranscriptional regulation of cotransmission

Science Advances, Journal Year: 2023, Volume and Issue: 9(22)

Published: June 2, 2023

While neurotransmitter identity was once considered singular and immutable for mature neurons, it is now appreciated that one neuron can release multiple neuroactive substances (cotransmission) whose identities even change over time. To explore the mechanisms tune suite of transmitters a releases, we developed transcriptional translational reporters cholinergic, glutamatergic, GABAergic signaling in Drosophila. We show many glutamatergic cells also transcribe cholinergic genes, but fail to accumulate effector proteins. Suppression involves posttranscriptional regulation transcripts by microRNA miR-190; chronic loss miR-190 function allows expression machinery, reducing fragmenting sleep. Using "translation-trap" strategy, neurons these populations have episodes transient translation proteins, demonstrating suppression cotransmission actively modulated. Posttranscriptional restriction fast transmitter provides mechanism allowing reversible tuning neuronal output.

Language: Английский

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Activity Monitoring for Analysis of Sleep inDrosophila melanogaster

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

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Neuroparasitology of Parasite–Insect Associations

Annual Review of Entomology, Journal Year: 2018, Volume and Issue: 63(1), P. 471 - 487

Published: Jan. 7, 2018

Insect behavior can be manipulated by parasites, and in many cases, such manipulation involves the central peripheral nervous system. Neuroparasitology is an emerging branch of biology that deals with parasites control system their host. The diversity manipulate insect ranges from viruses to macroscopic worms also includes other insects have evolved become (notably, parasitic wasps). It remarkable precise observed does not require direct entry into brain even occur when parasite outside body. We suggest a spatial view provides holistic approach examining interactions. Integration across approaches natural history advanced imaging techniques, omics, experiments will provide new vistas neuroparasitology. for researchers interested proximate mechanisms behaviors, studies significant value.

Language: Английский

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A Conserved Circadian Function for the Neurofibromatosis 1 Gene

Cell Reports, Journal Year: 2018, Volume and Issue: 22(13), P. 3416 - 3426

Published: March 1, 2018

Loss of the Neurofibromatosis 1 (Nf1) protein, neurofibromin, in Drosophila disrupts circadian rhythms locomotor activity without impairing central clock function, suggesting effects downstream clock. However, relevant cellular mechanisms are not known. Leveraging discovery output circuits for rhythms, we dissected actions neurofibromin recently identified substrates. Herein, show that affects levels and cycling calcium multiple peptidergic neurons. A prominent site action is pars intercerebralis (PI), fly equivalent hypothalamus, with cell-autonomous Nf1 PI cells secrete DH44. interacts genetically peptide signaling to affect behavior. We extended these studies mammals demonstrate mouse astrocytes exhibit a 24-hr rhythm levels, which also attenuated by lack neurofibromin. These findings establish conserved role intracellular within nervous system.

Language: Английский

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