Neural connectivity molecules best identify the heterogeneous clock and dopaminergic cell types in the Drosophila adult brain

Science Advances, Journal Year: 2023, Volume and Issue: 9(8)

Published: Feb. 22, 2023

Our recent single-cell sequencing of most adult

Language: Английский

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The neuropeptide pigment‐dispersing factor signals independently of Bruchpilot‐labelled active zones in daily remodelled terminals of Drosophila clock neurons

European Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 59(10), P. 2665 - 2685

Published: Feb. 27, 2024

Abstract The small ventrolateral neurons (sLNvs) are key components of the central clock in Drosophila brain. They signal via neuropeptide pigment‐dispersing factor (PDF) to align molecular clockwork different and modulate downstream circuits. dorsal terminals sLNvs undergo daily morphological changes that affect presynaptic sites organised by active zone protein Bruchpilot (BRP), a homolog mammalian ELKS proteins. However, role these for PDF release is ill‐defined. Here, we combined expansion microscopy with labelling zones endogenously tagged BRP examine spatial correlation between PDF‐containing dense‐core vesicles BRP‐labelled zones. We found number puncta sLNv was similar while their density differed Zeitgeber time (ZT) 2 14. relative distance BRP‐ PDF‐labelled increased morning, around reported release. Spontaneous vesicle profiles publicly available ssTEM dataset (FAFB) consistently lacked BRP‐organised RNAi‐mediated downregulation brp other proteins expressed did not PDF‐dependent locomotor rhythmicity. In contrast, down‐regulation genes encoding canonical machinery, vesicle‐related CADPS, as well impaired Taken together, our study suggests from independent zones, may be redistributed time‐dependent manner.

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

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

Published: Oct. 22, 2024

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

Language: Английский

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Circadian clock disruption promotes the degeneration of dopaminergic neurons in male Drosophila

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 22, 2023

Abstract Sleep and circadian rhythm disruptions are frequent comorbidities of Parkinson’s disease (PD), a disorder characterized by the progressive loss dopaminergic (DA) neurons in substantia nigra. However, causal role clocks degenerative process remains uncertain. We demonstrated here that regulate rhythmicity magnitude vulnerability DA to oxidative stress male Drosophila . Circadian pacemaker presynaptic subset rhythmically modulate their susceptibility degeneration. The arrhythmic period ( per ) gene null mutation exacerbates age-dependent and, combination with brief stress, causes premature animal death. These findings suggest clock disruption promotes neurodegeneration.

Language: Английский

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A subclass of evening cells promotes the switch from arousal to sleep at dusk

Current Biology, Journal Year: 2024, Volume and Issue: 34(10), P. 2186 - 2199.e3

Published: May 1, 2024

Language: Английский

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The Circadian Neuropeptide PDF has Sexually Dimorphic Effects on Activity Rhythms

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

Published: Feb. 1, 2024

The circadian system regulates the timing of multiple molecular, physiological, metabolic, and behavioral phenomena. In Drosophila as in other species, most research on how timekeeping brain controls outputs has been conducted males, or sex was not included a biological variable. main pacemaker neurons release neuropeptide Pigment Dispersing Factor (PDF), which functions key synchronizing factor network with complex effects clock neurons. Lack Pdf its receptor, PdfR, results flies displaying arrhythmicity activity-rest cycles under constant conditions. However, our show that female rhythms are less affected by mutations both PdfR. Crispr-Cas9 mutagenesis specifically ventral lateral (LNvs) also greater effect male rhythms. We tested influence M-cells over speeding up molecular leads to sexually dimorphic phenotypes, more pronounced rhythmic behavior. Our suggest is resilient manipulations PDF pathway distributed across neuron females.

Language: Английский

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Tango-seq: overlaying transcriptomics on connectomics to identify neurons downstream of Drosophila clock neurons

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

Published: May 22, 2024

Summary Knowing how neural circuits change with neuronal plasticity and differ between individuals is important to fully understand behavior. Connectomes are typically assembled using electron microscopy, but this low throughput impractical for analyzing or mutations. Here, we modified the trans -Tango genetic circuit-tracing technique identify neurons synaptically downstream of Drosophila s-LNv clock neurons, which show 24hr rhythms. target were labeled specifically in adult flies a nuclear reporter gene, facilitated their purification then single cell sequencing. We call Tango-seq, it allows transcriptomic data – thus identity be overlayed on top anatomical data. found that s-LNvs preferentially make synaptic connections subset CNMa+ DN1p these likely plastic connections. also identified mushroom body Kenyon cells. Tango-seq should useful addition connectomics toolkit.

Language: Английский

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Photoperiodic plasticity of pigment-dispersing factor immunoreactive fibers projecting toward prothoracicotropic hormone neurons in flesh fly Sarcophaga similis larvae

Journal of Comparative Physiology A, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Larvae of the flesh fly, Sarcophaga similis exhibit photoperiodic responses to control pupal diapause. Although external coincidence model is applicable S. photoperiodism, it remains unknown how circadian clock system integrates day-length information. To explore mechanisms, we examined neural circuitry involving lateral neurons (LNs) and prothoracicotropic hormone (PTTH) neurons. We also effects on LN-fiber patterns in third-instar larvae. Immunohistochemistry showed that protein PERIOD neuropeptide pigment-dispersing factor (PDF) were co-localized four cells per brain hemisphere, named these PDF-LNs similis. Single-cell polymerase chain reaction backfilled from ring gland two pairs pars lateralis with contralateral axons (PL-c neurons) expressed ptth. Double labeling immunohistochemistry backfills revealed PDF-immunoreactive varicose fibers projected close PL-c short f (snpf) receptor glutamate-gated chloride channel but not pdf sNPF L-glutamate PDF acutely inhibited spontaneous firing activity The number varicosities dorsal protocerebrum was significantly higher under short-day than long-day conditions a time-dependent manner. These results suggest and/or glutamate signaling PTTH form potential circuity for diapause photoperiod modifies connectivity strength between their post- or pre-neurons circuitry.

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 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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Synaptic Targets of Circadian Clock Neurons Influence Core Clock Parameters

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Neuronal connectivity in the circadian clock network is essential for robust endogenous timekeeping. In Drosophila network, four pairs of small ventral lateral neurons (sLNvs) serve as main pacemakers. Peptidergic communication via sLNv, which release key output neuropeptide, Pigment Dispersing Factor (PDF), has been well characterized. absence PDF, flies become largely arrhythmic, similar to phenotype associated with loss mammalian peptide, VIP. contrast, little known about role synaptic connections that sLNvs form downstream neurons. Connectomic analyses revealed despite their pacemaker within very few monosynaptic other However, they strong a group previously uncharacterized neurons, SLP316, turn synapse onto dorsal Here, we show silencing SLP316 tetanus toxin (TNT) expression shortens free-running period, whereas hyper-exciting them by expressing constitutively open Na[+] channel, NaChBac, results period lengthening. Under light-dark cycles, also causes lower daytime activity and higher sleep, likely due increased sleep pressure. Our postsynaptic partners are non-clock neuronal cell type regulates timing activity.

Language: Английский

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