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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Endocrine cybernetics: neuropeptides as molecular switches in behavioural decisions

Open Biology, Journal Year: 2022, Volume and Issue: 12(7)

Published: July 1, 2022

Plasticity in animal behaviour relies on the ability to integrate external and internal cues from changing environment hence modulate activity synaptic circuits of brain. This context-dependent neuromodulation is largely based non-synaptic signalling with neuropeptides. Here, we describe select peptidergic systems Drosophila brain that act at different levels a hierarchy associated physiology. These regions, such as central complex mushroom bodies, which supervise specific behaviours. At top level there are small numbers large neurons arborize widely multiple areas orchestrate or global state manner. bottom local provide executive sensory gain intrinsically restricted parts neuronal circuits. The orchestrating receive interoceptive signals mediate energy sleep homeostasis, metabolic circadian timing, well affect food search, aggression mating. Some these can be triggers conflicting behaviours mating versus aggression, feeding, participate circuits, enabling choices switches.

Language: Английский

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Seasonal cues act through the circadian clock and pigment-dispersing factor to control EYES ABSENT and downstream physiological changes

Current Biology, Journal Year: 2023, Volume and Issue: 33(4), P. 675 - 687.e5

Published: Jan. 27, 2023

Language: Английский

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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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Synaptic connectome of the Drosophila circadian clock

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

Published: Dec. 5, 2024

Abstract The circadian clock and its output pathways play a pivotal role in optimizing daily processes. To obtain insights into how diverse rhythmic physiology behaviors are orchestrated, we have generated comprehensive connectivity map of an animal using the Drosophila FlyWire brain connectome. Intriguingly, identified additional dorsal neurons, thus showing that network contains ~240 instead 150 neurons. We revealed extensive contralateral synaptic within discovered novel indirect light input to also elucidated via which modulates descending neurons known regulate feeding reproductive behaviors. Interestingly, observed sparse monosynaptic between downstream higher-order centers neurosecretory cells behavior physiology. Therefore, integrated single-cell transcriptomics receptor mapping decipher putative paracrine peptidergic signaling by Our analyses neuropeptides expressed suggest significantly enriches interconnectivity network.

Language: Английский

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Mutual coupling of neurons in the circadian master clock: what we can learn from fruit flies

Neurobiology of Sleep and Circadian Rhythms, Journal Year: 2025, Volume and Issue: 18, P. 100112 - 100112

Published: Jan. 18, 2025

Circadian master clocks in the brain consist of multiple neurons that are organized into populations with different morphology, physiology, and neuromessenger content presumably functions. In most animals, these distributed bilaterally, located close proximity to visual system, synchronized by eyes light-dark cycles environment. mammals cockroaches, each two consists a core region receives information from shell which output projections originate, whereas flies several other insects, lateral dorsal regions. all cases, morning evening clock seem exist, communication between them neurons, as well connection across hemispheres, is prerequisite for normal rhythmic function. Phenomena such rhythm splitting, internal desynchronization caused "decoupling" hemispheres or decoupling certain within one hemisphere. Since contain relatively few characterized at individual level, fly particularly suited study neurons. Here, we review organization bilateral brain, focus on synaptic paracrine connections comparison insects mammals.

Language: Английский

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Neural mechanisms of parasite-induced summiting behavior in ‘zombie’ Drosophila

eLife, Journal Year: 2023, Volume and Issue: 12

Published: May 15, 2023

For at least two centuries, scientists have been enthralled by the "zombie" behaviors induced mind-controlling parasites. Despite this interest, mechanistic bases of these uncanny processes remained mostly a mystery. Here, we leverage

Language: Английский

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Synaptic connectome of theDrosophilacircadian clock

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 13, 2023

The circadian clock and its output pathways play a pivotal role in optimizing daily processes. To obtain novel insights into how diverse rhythmic physiology behaviors are orchestrated, we have generated the first comprehensive connectivity map of an animal using Drosophila FlyWire brain connectome. Intriguingly, identified additional dorsal neurons, thus showing that network contains ∼240 instead 150 neurons. We also revealed extensive contralateral synaptic within discovered indirect light input to Interestingly, observed sparse monosynaptic between neurons down-stream higher-order centers neurosecretory cells known regulate behavior physiology. Therefore, integrated single-cell transcriptomics receptor mapping decipher putative paracrine peptidergic signaling by Our analyses neuropeptides expressed suggest significantly enriches interconnectivity network.

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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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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