The emergence and influence of internal states

Neuron, Journal Year: 2022, Volume and Issue: 110(16), P. 2545 - 2570

Published: May 27, 2022

Language: Английский

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A neuron–glia lipid metabolic cycle couples daily sleep to mitochondrial homeostasis

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(4), P. 666 - 678

Published: Feb. 15, 2024

Abstract Sleep is thought to be restorative brain energy homeostasis, but it not clear how this achieved. We show here that Drosophila glia exhibit a daily cycle of glial mitochondrial oxidation and lipid accumulation dependent on prior wake requires the APOE orthologs NLaz GLaz, which mediate neuron–glia transfer. In turn, full night sleep required for clearance, oxidative recovery maximal neuronal mitophagy. Knockdown causes stress accumulate in neurons, integrity protein, Drp1, accumulation. These data suggest neurons avoid damage during by using mitophagy passing form lipids. propose metabolic between reflects fundamental function relevant homeostasis.

Language: Английский

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Sleep and circadian rhythmicity as entangled processes serving homeostasis

Nature reviews. Neuroscience, Journal Year: 2023, Volume and Issue: 25(1), P. 43 - 59

Published: Dec. 1, 2023

Language: Английский

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Cell type-specific driver lines targeting the Drosophila central complex and their use to investigate neuropeptide expression and sleep regulation

Published: Jan. 21, 2025

The central complex (CX) plays a key role in many higher-order functions of the insect brain including navigation and activity regulation. Genetic tools for manipulating individual cell types, knowledge what neurotransmitters neuromodulators they express, will be required to gain mechanistic understanding how these are implemented. We generated characterized split-GAL4 driver lines that express or small subsets about half CX types. surveyed neuropeptide receptor expression using fluorescent situ hybridization. About neuropeptides we examined were expressed only few cells, while rest dozens hundreds cells. Neuropeptide receptors more broadly at lower levels. Using our GAL4 drivers mark found 51 85 types least one 21 multiple neuropeptides. Surprisingly, all co-expressed molecule neurotransmitter. Finally, used identify whose activation affects sleep, identified other link circadian clock CX. well-characterized genetic information on neurotransmitter provide should enhance studies

Language: Английский

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The dorsal fan-shaped body is a neurochemically heterogeneous sleep-regulating center in Drosophila

PLoS Biology, Journal Year: 2025, Volume and Issue: 23(3), P. e3003014 - e3003014

Published: March 26, 2025

Sleep is a behavior that conserved throughout the animal kingdom. Yet, despite extensive studies in humans and models, exact function or functions of sleep remain(s) unknown. A complicating factor trying to elucidate complexity multiplicity neuronal circuits are involved regulation. It conceivable distinct sleep-regulating only specific aspects may underlie different functions. Thus, it would be beneficial assess contribution individual sleep’s putative The intricacy mammalian brain makes this task extremely difficult. However, fruit fly Drosophila melanogaster, with its simpler organization, available connectomics, unparalleled genetics, offers opportunity interrogate centers. In , neurons projecting dorsal fan-shaped body (dFB) have been proposed key regulators sleep, particularly homeostasis. We recently demonstrated most widely used genetic tool manipulate dFB neurons, 23E10-GAL4 driver, expresses 2 (VNC-SP neurons) located ventral nerve cord (VNC), analog vertebrate spinal cord. Since data supporting role for regulation obtained using 23E10-GAL4, unclear whether phenotypes reported these caused by VNC-SP cells. recent publication replicated our finding contains sleep-promoting VNC. also not at all, but suggestion was made tools dFB-specific very mild deprivation protocol. study, newly created driver line, we demonstrate optogenetic activation majority promotes show require stronger stimulation than cells promote sleep. addition, dFB-induced can consolidate short-term memory (STM) into long-term (LTM), suggesting benefit on circuit-specific. Finally, neurochemically heterogeneous divided 3 populations. Most express both glutamate acetylcholine, while minority one neurotransmitters. Importantly, do GABA, as previously suggested. Using neurotransmitter-specific tools, points cholinergic potent regulating

Language: Английский

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Connectomic analysis of the Drosophila lateral neuron clock cells reveals the synaptic basis of functional pacemaker classes

eLife, Journal Year: 2022, Volume and Issue: 11

Published: June 29, 2022

The circadian clock orchestrates daily changes in physiology and behavior to ensure internal temporal order optimal timing across the day. In animals, a central brain coordinates rhythms throughout body is characterized by remarkable robustness that depends on synaptic connections between constituent neurons. neuron network of Drosophila, which shares motifs with networks mammalian yet built many fewer neurons, offers powerful model for understanding properties timekeeping. Here, we report an assessment connectivity within network, focusing critical lateral (LN) classes Janelia hemibrain dataset. Our results reveal previously identified anatomical functional subclasses LNs represent distinct connectomic types. Moreover, identify small number non-clock cell subtypes representing highly synaptically coupled nodes network. This suggests neurons lacking molecular timekeeping likely play integral roles To our knowledge, this represents first comprehensive analysis neuronal network.Most organisms Earth possess system ensures bodily processes such as sleep, wakefulness or digestion take place at right time. These precise are kept check master brain. There, thousands – some carrying ‘molecular clock’ connect each other through structures known synapses. Exactly how resulting organised support remains unclear. explore question, Shafer, Gutierrez et al. focused fruit flies, recent efforts have systematically mapped every connection organism. Analysing available data from connectome project revealed most important were fact forming fewest synapses addition, without clocks mediated strong those did, suggesting ‘clockless’ cells still role With research, provide unexpected insights into organisation clock. Better underpin will help grasp why these disrupted obesity, depression Alzheimer’s disease.

Language: Английский

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A gut-secreted peptide suppresses arousability from sleep

Cell, Journal Year: 2023, Volume and Issue: 186(7), P. 1382 - 1397.e21

Published: March 1, 2023

Language: Английский

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Variant-to-gene mapping followed by cross-species genetic screening identifies GPI-anchor biosynthesis as a regulator of sleep

Science Advances, Journal Year: 2023, Volume and Issue: 9(1)

Published: Jan. 6, 2023

Genome-wide association studies (GWAS) in humans have identified loci robustly associated with several heritable diseases or traits, yet little is known about the functional roles of underlying causal variants regulating sleep duration quality. We applied an ATAC-seq/promoter focused Capture C strategy human iPSC-derived neural progenitors to carry out a "variant-to-gene" mapping campaign that 88 candidate effector genes connected relevant GWAS signals. To functionally validate role implicated regulation, we performed neuron-specific RNA interference screen fruit fly,

Language: Английский

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Regulation of sleep by cholinergic neurons located outside the central brain in Drosophila

PLoS Biology, Journal Year: 2023, Volume and Issue: 21(3), P. e3002012 - e3002012

Published: March 2, 2023

Sleep is a complex and plastic behavior regulated by multiple brain regions influenced numerous internal external stimuli. Thus, to fully uncover the function(s) of sleep, cellular resolution sleep-regulating neurons needs be achieved. Doing so will help unequivocally assign role or function given neuron group in sleep behavior. In Drosophila brain, projecting dorsal fan-shaped body (dFB) have emerged as key area. To dissect contribution individual dFB we undertook an intersectional Split-GAL4 genetic screen focusing on cells contained within 23E10-GAL4 driver, most widely used tool manipulate neurons. this study, demonstrate that expresses outside fly equivalent spinal cord, ventral nerve cord (VNC). Furthermore, show 2 VNC cholinergic strongly contribute sleep-promoting capacity driver under baseline conditions. However, contrast other neurons, silencing these does not block homeostasis. our data contains at least different types controlling distinct aspects

Language: Английский

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Re-examining the role of the dorsal fan-shaped body in promoting sleep in Drosophila

Current Biology, Journal Year: 2023, Volume and Issue: 33(17), P. 3660 - 3668.e4

Published: Aug. 7, 2023

The needs fulfilled by sleep are unknown, though the effects of insufficient manifold. To better understand how need to is sensed and discharged, much effort has gone into identifying neural circuits involved in regulating arousal, especially those that promote sleep. In prevailing models, dorsal fan-shaped body (dFB) plays a central role this process fly brain. present study we manipulated various properties dFB including its electrical activity, synaptic output, endogenous gene expression. each these experimental contexts were unable identify any effect on could be unambiguously mapped dFB. Furthermore, found evidence phenotypes previously attributed caused genetic manipulations inadvertently targeted ventral nerve cord. We also examined expression two genes whose purported have been functions within specific subpopulation neurons. both cases little no expected cells. Collectively, our results cast doubt hypothesis promoting

Language: Английский

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