Lessons from lonely flies: Molecular and neuronal mechanisms underlying social isolation

Neuroscience & Biobehavioral Reviews, Journal Year: 2023, Volume and Issue: 156, P. 105504 - 105504

Published: Dec. 6, 2023

Animals respond to changes in the environment which affect their internal state by adapting behaviors. Social isolation is a form of passive environmental stressor that alters animal behaviors across kingdom, including humans, rodents, and fruit flies. known increase violence, disrupt sleep depression leading poor mental physical health. Recent evidence from several model organisms suggests social leads remodeling transcriptional epigenetic landscape behavioral outcomes. In this review, we explore how manipulating experience fly Drosophila melanogaster can shed light on molecular neuronal mechanisms underlying driven We discuss recent advances made using powerful genetic toolkit assays uncover role neuromodulators, sensory modalities, pheromones, circuits mediating isolation. The insights gained these studies could be crucial for developing effective therapeutic interventions future.

Language: Английский

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Constitutive and conditional epitope-tagging of endogenous G protein coupled receptors inDrosophila

Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 44(33), P. e2377232024 - e2377232024

Published: June 27, 2024

To visualize the cellular and subcellular localization of neuromodulatory G-protein–coupled receptors in Drosophila , we implement a molecular strategy recently used to add epitope tags ionotropic at their endogenous loci. Leveraging evolutionary conservation identify sites more likely permit insertion tag, generated constitutive conditional tagged alleles for 5-HT1A 5-HT2A 5-HT2B Oct β 1R 2R two isoforms OAMB mGluR . The allow restricted expression receptor specific cell types, an option not available any previous reagents label these proteins. We show patterns female brains that localize mushroom bodies (MBs) central complex, respectively, as predicted by roles sleep. By contrast, unexpected enrichment Octβ1R complex nerve terminals lobular columnar cells visual system suggest new hypotheses about functions sites. Using additional allele serotonin transporter, marker serotonergic tracts, demonstrate diverse spatial relationships between postsynaptic 5-HT presynaptic neurons, consistent with importance both synaptic volume transmission. Finally, use it localizes distinct within MBs Kenyon autoreceptor.

Language: Английский

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Sex- and age-dependent associations of EPA and DHA with very short sleep duration in adults: a cross-sectional analysis

Nutritional Neuroscience, Journal Year: 2024, Volume and Issue: 27(10), P. 1113 - 1122

Published: Feb. 9, 2024

Objectives This study aimed to compare the efficacy of dietary intake eicosapentaenoic acid (EPA; 20:5 ω-3) and docosahexaenoic (DHA; 22:6 on very short sleep duration (<5 h/night) in adults.

Language: Английский

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Biogenic amines and their receptors in insects

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Homeostatic Control of Deep Sleep and Molecular Correlates of Sleep Pressure in Drosophila

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

Published: Oct. 31, 2023

Homeostatic control of sleep is typically addressed through mechanical stimulation-induced forced wakefulness and the measurement subsequent increases in sleep. A major confound attends this approach: biological responses to deprivation may reflect a direct response insult rather than loss Similar confounds accompany all forms represent challenge field. Here, we describe new paradigm for Drosophila that fully accounts sleep-independent effects. Our results reveal deep states are primary target homeostatic establish presence multi-cycle rebound following deprivation. Furthermore, specific state-specific rebound. Finally, by accounting molecular effects stimulation during experiments, show serotonin levels track pressure fly's central brain. illustrate critical need when examining correlates call reassessment work has not accounted such non-specific

Language: Английский

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Transcriptional changes in specific subsets of Drosophila neurons following inhibition of the serotonin transporter

Translational Psychiatry, Journal Year: 2023, Volume and Issue: 13(1)

Published: June 24, 2023

The transcriptional effects of SSRIs and other serotonergic drugs remain unclear, in part due to the heterogeneity postsynaptic cells, which may respond differently changes signaling. Relatively simple model systems such as Drosophila afford more tractable microcircuits investigate these specific cell types. Here, we focus on mushroom body, an insect brain structure heavily innervated by serotonin comprised multiple different but related subtypes Kenyon cells. We use fluorescence-activated sorting followed either bulk or single-cell RNA sequencing explore transcriptomic response cells SERT inhibition. compared two Serotonin Transporter (dSERT) mutant alleles well feeding SSRI citalopram adult flies. find that genetic architecture associated with one mutants contributed significant artefactual expression. Comparison differential expression caused loss during development versus aged, flies, suggests signaling have relatively stronger development, consistent behavioral studies mice. Overall, our experiments revealed limited suggest loss-of-function. Further work exploring loss-of-function circuits be used help elucidate how differentially affect a variety neuronal both adults.

Language: Английский

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Microdosing ketamine in Drosophila does not block serotonin reuptake, but causes complex behavioral changes mediated by glutamate and serotonin receptors

Journal of Neurochemistry, Journal Year: 2024, Volume and Issue: 168(6), P. 1097 - 1112

Published: Feb. 7, 2024

Abstract Microdosing ketamine is a novel antidepressant for treatment‐resistant depression. Traditional antidepressants, like selective serotonin reuptake inhibitors (SSRIs), inhibit reuptake, but it not clear if shows similar mechanism. Here, we tested the effects of feeding and SSRIs to Drosophila melanogaster larvae, which has system mammals good model track depressive behaviors, such as locomotion feeding. Fast‐scan cyclic voltammetry (FSCV) was used measure optogenetically stimulated changes, tracking software blue dye monitor behavior. We fed larvae various doses (1–100 mM) antidepressants 24 h found that 1 mM did affect serotonin, increased Low (≤10 escitalopram fluoxetine inhibited dSERT also behaviors. At 100 mM, concentrations, decreased because its anesthetic properties. Since microdosing causes behavioral effects, further investigated changes with SERT16 mutant low other NMDA receptor antagonists 5‐HT 1A 2 agonists. Feeding were in mutant, antagonism feeding, while agonism locomotion, could explain these ketamine. Ultimately, this work discern mechanisms, does on SSRIs, behavior mechanisms should be further. image

Language: Английский

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Elevated sleep quota in a stress-resilient Drosophila species

Current Biology, Journal Year: 2024, Volume and Issue: 34(11), P. 2487 - 2501.e3

Published: May 20, 2024

Sleep is broadly conserved across the animal kingdom but can vary widely between species. It currently unclear which selective pressures and regulatory mechanisms influence differences in sleep The fruit fly Drosophila melanogaster has become a successful model system for examining regulation function, little known about patterns many related Here, we find that species with adaptations to extreme desert environments, including D. mojavensis, exhibit strong increases baseline compared melanogaster. Long-sleeping mojavensis show intact homeostasis, indicating flies carry an elevated drive sleep. In addition, altered abundance or distribution of several sleep/wake-related neuromodulators neuropeptides are consistent their reduced locomotor activity increased Finally, nutrient-deprived environment, individual strongly correlated survival time disrupting via constant light stimulation renders more sensitive starvation. Our results demonstrate novel studying organisms high exploring strategies provide resilience environments.

Language: Английский

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Behavioral Dysfunctions Caused by Pyridoxamine Deficiency in <i>Drosophila melanogaster</i>

Journal of Nutritional Science and Vitaminology, Journal Year: 2024, Volume and Issue: 70(3), P. 252 - 261

Published: June 29, 2024

Pyridoxamine (PM) is one of the natural vitamins B6 (VB6) and functions as an endogenous inhibitor for formation AGEs (advanced glycation end products). The are implicated in aging, diabetes, various neuropsychiatric disease, including schizophrenia, Alzheimer's Parkinson's disease. However, it unclear whether absence PM per se accumulates vivo causes behavioral dysfunctions. To address these points, we raised PM-deficient fruit flies, Drosophila melanogaster, with sterilized defined medium. Flies reared a medium accumulated reduced lifespan, impaired gustatory response, sleep, courtship behavior, olfactory learning. These results suggest that suppresses AGE accumulation required regulating innate empirical behaviors.

Language: Английский

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Neural circuit plasticity underlying learning and memory in Drosophila melanogaster: from synaptic connections to behavior

Published: Jan. 1, 2023

Understanding the principles behind olfactory higher-order associative chains formation in Drosophila is one step further into unraveling essence of learning and memory. However, rationale such mechanisms sprouts since development young brain to its full potential ability form complex intermingled connections governing this type learning. First, we took a developmental approach assess activity neuronal center fruit fly, mushroom body (MB). We could demonstrate that pruning remodelling MB, are necessary for healthy development, occur by hyperpolarisation cell-autonomous external factors. The interruption processes leads poor MB along with synaptic partners, thus translating deficit memory adult stage. Then, worked towards scrutinizing plasticity underlying context classical aversive conditioning paradigm second manuscript. show association conditioned stimulus (i.e. odor) punishment electric shocks) localized changes between odor encoding cells (Kenyon KCs) behavioral mediating output neurons (MB MBONs) distinct compartment γ1. In third last manuscript, designated second-order (SOC) as unravel get closer understanding SOC can be achieved when previously (CS1) paired second-conditioned (CS2), eliciting response CS2. This offers opportunity examine how internal transfer information from CS1 CS2 occurs on cellular molecular levels. Therefore, investigating yet unclear microcircuit underlies behavior importance. By thermo-genetically manipulating populations, microcircuits implicated during different phases training test SOC. functional imaging connectomics analysis procured better dynamics candidate neurons, which emerges proposed model suggest two parallel compartments work synergy allowing through bidirectional feedback loops hijack punishment-mediating dopaminergic associations.

Language: Английский

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