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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The CHD8/CHD7/Kismet family links blood-brain barrier glia and serotonin to ASD-associated sleep defects

Science Advances, Journal Year: 2021, Volume and Issue: 7(23)

Published: June 4, 2021

Autism-associated CHD8/CHD7/kismet deficiency in blood-brain barrier glia causes developmental hyperserotonemia and sleep defects.

Language: Английский

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Mutation of the Drosophila melanogaster serotonin transporter dSERT impacts sleep, courtship, and feeding behaviors

PLoS Genetics, Journal Year: 2022, Volume and Issue: 18(11), P. e1010289 - e1010289

Published: Nov. 21, 2022

The Serotonin Transporter (SERT) regulates extracellular serotonin levels and is the target of most current drugs used to treat depression. mechanisms by which inhibition SERT activity influences behavior are poorly understood. To address this question in model organism Drosophila melanogaster , we developed new loss function mutations ( dSERT) . Previous studies both flies mammals have implicated as an important neuromodulator sleep, our newly generated dSERT mutants show increase total sleep altered architecture that mimicked feeding SSRI citalopram. Differences daytime versus nighttime well genetic rescue experiments unexpectedly suggest distinct serotonergic circuits may modulate sleep. also defects copulation food intake, akin clinical side effects SSRIs consistent with pleomorphic influence on D Starvation did not overcome drive male mutants, mate failed drive. be further explore its interplay other complex behaviors.

Language: Английский

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Developmental emergence of sleep rhythms enables long-term memory in Drosophila

Science Advances, Journal Year: 2023, Volume and Issue: 9(36)

Published: Sept. 8, 2023

In adulthood, sleep-wake rhythms are one of the most prominent behaviors under circadian control. However, during early life, sleep is spread across 24-hour day. The mechanism through which emerge, and consequent advantage conferred to a juvenile animal, unknown. second-instar Drosophila larvae (L2), like in human infants, not We identify precise developmental time point when clock begins regulate Drosophila, leading emergence third-instars (L3). At this stage, cellular connection forms between DN1a neurons arousal-promoting Dh44 neurons, bringing arousal control drive sleep. Last, we demonstrate that L3 but L2 exhibit long-term memory (LTM) aversive cues LTM depends upon deep generated once begin. propose enables more complex cognitive processes, including onset enduring memories.

Language: Английский

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Divergent evolution of sleep functions

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

Published: May 28, 2023

Abstract Most living organisms have evolved to synchronize their biological activities with the earth’s rotation, a daily regulation of biology and behaviour controlled by an evolutionary conserved molecular machinery known as circadian clock. For most animals, mechanisms are meant maximize exposure positive ( e.g.: social interactions, mating, feeding – generally during day) minimize peril predation, weather, darkness night 1 ). On top regulation, some behaviours also feature second layer homeostatic control acting fail-safe ensure important not ignored. Sleep is one these behaviours: largely clock for its baseline appearance, it at same time modulated poorly understood regulator ensuring animals obey species-specific amount sleep 2 . An often considered main evidence core function beyond trivial (that is: keeping us out trouble limiting our energy expenditure danger 3,4 ) hypothesized that around this mysterious basic function. Here we characterize in group seven species Drosophila genus key distances representing variety ecological niche adaptations. We show spontaneous circadian-driven aspects among all but unexpectedly, not. uncover differences behavioural, cell-biological neuro-pharmacological suggest that, Drosophilids, primarily satisfy role, immobile dangerous hours day. The functions independently, fashion, conserved.

Language: Английский

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Experimentally induced active and quiet sleep engage non-overlapping transcriptional programs in Drosophila

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

Published: June 14, 2023

Sleep in mammals can be broadly classified into two different physiological categories: rapid eye movement (REM) sleep and slow-wave (SWS), accordingly REM SWS are thought to achieve a set of functions. The fruit fly Drosophila melanogaster is increasingly being used as model understand functions, although it remains unclear if the brain also engages kinds well. Here, we compare commonly approaches for studying experimentally : optogenetic activation sleep-promoting neurons provision drug, gaboxadol. We find that these sleep-induction methods have similar effects on increasing duration, but divergent activity. Transcriptomic analysis reveals drug-induced deep (‘quiet’ sleep) mostly downregulates metabolism genes, whereas ‘active’ upregulates wide range genes relevant normal waking This suggests optogenetics pharmacological induction promote features sleep, which engage sets their respective

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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The Roles of Discrete Populations of Neurons Expressing Short Neuropeptide F in Sleep Induction in Drosophila melanogaster

Genes Brain & Behavior, Journal Year: 2025, Volume and Issue: 24(1)

Published: Feb. 1, 2025

Sleep is of vital importance in our lives, yet we are far from understanding the neuronal networks that control amount and timing sleep. There substantial conservation known sleep-regulating transmitters, allowing for studies simpler organisms to lead way gaining insight into organization sleep circuits. In Drosophila melanogaster, recently showed optogenetic activation neurons produce neuropeptide Y (NPY)-related transmitter short F (sNPF) increases time spent asleep. However, sNPF expressed several populations, thus it unknown which those populations play roles sleep-promoting effect. this study, addressed issue using a genetic approach limit subsets sNPF-expressing neurons. We found promotion was shorter-lived when cryptochrome (CRY)-positive were excluded being activated. Pigment-dispersing factor (PDF) not required promotion, nor mushroom body (MB) Acute reactions short, 10-s period largely unchanged by excluding three mentioned above. Together, these results suggest clock CRY-positive PDF-negative important contributors long-lasting produced neuron activation. other targeted sNPF-GAL4 driver appear mediate more rapid behavioral responses. Future will seek identify additional determine how act concert with circuits promote

Language: Английский

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Brief disruption of activity in a subset of dopaminergic neurons during consolidation impairs long-term memory by fragmenting sleep

Published: March 12, 2025

Sleep disturbances are associated with poor long-term memory (LTM) formation, yet the underlying cell types and neural circuits involved have not been fully decoded. Dopamine neurons (DANs) in processing at multiple stages. Here, using both male female flies, Drosophila melanogaster , we show that, during first few hours of consolidation, disruption basal activity a small subset protocerebral anterior medial DANs (PAM-DANs), by either brief activation or inhibition two dorsal posterior (DPM) neurons, impairs 24 h LTM. Interestingly, these changes flies result sleep loss fragmentation, especially night. Pharmacological rescue after manipulation restores A specific PAM-DANs (PAM-α1) that synapse onto DPM specify microcircuit links memory. PAM-DANs, including PAM-α1, form functional synapses mainly via dopamine receptor subtypes. This PAM-α1 to exhibits synchronized, transient, post-training increase critical consolidation window, suggesting an effect this on maintaining necessary for LTM consolidation. Our results provide new cellular circuit basis complex relationship between

Language: Английский

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