A circadian output circuit controls sleep-wake arousal threshold in <i>Drosophila</i>

Guo, Fei; Holla, Meghana; Mm, Díaz; Rosbash, Michael

doi:10.1101/298067

Cited by 6 publications

(3 citation statements)

References 51 publications

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“…S2) using conventional water immersion objectives. ProExM has been applied to a range of model animals, including mouse (19), zebrafish (23), and Drosophila (24–28). While up to 20× expansion has been reported (29), at 8× expansion using a novel iterated form of the DMAA-gel expansion protocol, we observed regions where the expansion superficially appears accurate (fig.…”

Section: Combining Expansion and Lattice Light-sheet Microscopy (Exllsm)mentioning

confidence: 99%

Cortical column and whole-brain imaging with molecular contrast and nanoscale resolution

Gao

Asano

Upadhyayula

et al. 2019

Science

308

304

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Optical and electron microscopy have made tremendous inroads in understanding the complexity of the brain. However, optical microscopy offer insufficient resolution to reveal subcellular details and electron microscopy lacks the throughput and molecular contrast to visualize specific molecular constituents over mm-scale or larger dimensions. We combined expansion microscopy and lattice light-sheet microscopy to image the nanoscale spatial relationships between proteins across the thickness of the mouse cortex or the entire Drosophila brain. These included synaptic proteins at dendritic spines, myelination along axons, and presynaptic densities at dopaminergic neurons in every fly brain region. The technology should enable statistically rich, large scale studies of neural development, sexual dimorphism, degree of stereotypy, and structural correlations to behavior or neural activity, all with molecular contrast.

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Section: Combining Expansion and Lattice Light-sheet Microscopy (Exllsm)mentioning

confidence: 99%

Cortical column and whole-brain imaging with molecular contrast and nanoscale resolution

Gao

Asano

Upadhyayula

et al. 2019

Science

308

304

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“…As described above, hTau V337M /CS flies show increased wakefulness during the late evening and in the morning. Morning activity is largely determined by the small ventrolateral neurons (sLNvs) that express the Pigment dispersing factor (PDF) (Tataroglu and Emery, 2014;Guo et al, 2018). The sLNvs form a small group of neurons, with four neurons in each hemisphere, that send their axons in a well described pattern to the dorsomedial protocerebrum (arrows, Figure 3A) (Helfrich-Forster et al, 2007;Tomioka and Matsumoto, 2009).…”

Section: Axonal Terminals Of Central Pacemaker Neurons Are Altered Inmentioning

confidence: 99%

“…The PDF neurons regulate sleep as part of a network (Guo et al, 2018) and the changes in the termination pattern of the PDF neurons could therefore interfere with their connectivity with other neurons. PDF neurons show daily fluctuations in their connectivity, whereby synapses are potentiated during the day and altered or downscaled during sleep, a process generally referred to as "synaptic homeostasis" Cirelli, 2003, 2014).…”

Section: Tau V337m Interferes With Circadian Changes In the Morphologmentioning

confidence: 99%

Disease-Associated Mutant Tau Prevents Circadian Changes in the Cytoskeleton of Central Pacemaker Neurons

et al. 2020

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A hallmark feature of Alzheimer's disease (AD) and other Tauopathies, like Frontotemporal Dementia with Parkinsonism linked to chromosome 17 (FTDP-17), is the accumulation of neurofibrillary tangles composed of the microtubule-associated protein Tau. As in AD, symptoms of FTDP-17 include cognitive decline, neuronal degeneration, and disruptions of sleep patterns. However, mechanisms by which Tau may lead to these disturbances in sleep and activity patterns are unknown. To identify such mechanisms, we have generated novel Drosophila Tauopathy models by replacing endogenous fly dTau with normal human Tau (hTau) or the FTDP-17 causing hTau V337M mutation. This mutation is localized in one of the microtubule-binding domains of hTau and has a dominant effect. Analyzing heterozygous flies, we found that aged hTau V337M flies show neuronal degeneration and locomotion deficits when compared to wild type or hTau WT flies. Furthermore, hTau V337M flies are hyperactive and they show a fragmented sleep pattern. These changes in the sleep/activity pattern are accompanied by morphological changes in the projection pattern of the central pacemaker neurons. These neurons show daily fluctuations in their connectivity, whereby synapses are increased during the day and reduced during sleep. Synapse formation requires cytoskeletal changes that can be detected by the accumulation of the end-binding protein 1 (EB1) at the site of synapse formation. Whereas, hTau WT flies show the normal day/night changes in EB1 accumulation, hTau V337M flies do not show this fluctuation. This suggests that hTau V337M disrupts sleep patterns by interfering with the cytoskeletal changes that are required for the synaptic homeostasis of central pacemaker neurons.

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Opposing subclasses of Drosophila ellipsoid body neurons promote and suppress sleep

Aleman

Omoto

Singh

et al. 2021

Preprint

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SummaryRecent work in Drosophila has uncovered several neighboring classes of sleep-regulatory neurons within the central complex. However, the logic of connectivity and network motifs remains limited by the incomplete examination of relevant cell types. Using a recent genetic-anatomical classification of ellipsoid body ring neurons, we conducted a thermogenetic screen to assess sleep/wake behavior and discovered two opposing populations: sleep-promoting R3m and wake-promoting R3d neurons. Activation of these neurons influences sleep duration and architecture by prolonging or shortening sleep bouts, suggesting a key role in sleep maintenance. R3m and R3d neurons are GABAergic and require GABA synthesis for their effects on sleep. Finally, we use a fluorescent reporter for putative synaptic partners to embed these neurons within the known sleep-regulatory network; R3m and R3d neurons lay downstream of wake-active Helicon cells, and R3m neurons likely inhibit R3d neurons. Together, the data presented herein suggest a neural mechanism by which previously uncharacterized circuit elements operate within the sleep homeostat to stabilize sleep-wake states.

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A circadian output circuit controls sleep-wake arousal threshold in Drosophila

Cited by 6 publications

References 51 publications

Cortical column and whole-brain imaging with molecular contrast and nanoscale resolution

Cortical column and whole-brain imaging with molecular contrast and nanoscale resolution

Disease-Associated Mutant Tau Prevents Circadian Changes in the Cytoskeleton of Central Pacemaker Neurons

Opposing subclasses of Drosophila ellipsoid body neurons promote and suppress sleep

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