Fruit Fly Research Articles

Simultaneous Silencing of Gut Nucleases and a Vital Target Gene by Adult dsRNA Feeding Enhances RNAi Efficiency and Mortality in Ceratitis capitata.

Ceratitis capitata, known as the Mediterranean fruit fly (Medfly), is a major dipteran pest significantly impacting fruit and vegetable farming. Currently, its control heavily relies mainly on chemical insecticides, which pose health risks and have effects on pollinators. A more sustainable and species-specific alternative strategy may be based on double-stranded RNA (dsRNA) delivery through feeding to disrupt essential functions in pest insects, which is poorly reported in dipteran species. Previous reports in Orthoptera and Coleoptera species suggested that dsRNA degradation by specific nucleases in the intestinal lumen is among the major obstacles to feeding-mediated RNAi in insects. In our study, we experimented with three-day adult feeding using a combination of dsRNA molecules that target the expression of the ATPase vital gene and two intestinal dsRNA nucleases. These dsRNA molecules were recently tested separately in two Tephritidae species, showing limited effectiveness. In contrast, by simultaneously feeding dsRNA against the CcVha68-1, CcdsRNase1, and CcdsRNase2 genes, we observed 79% mortality over seven days, which was associated with a decrease in mRNA levels of the three targeted genes. As expected, we also observed a reduction in dsRNA degradation following RNAi against nucleases. This research illustrates the potential of utilizing molecules as pesticides to achieve mortality rates in Medfly adults by targeting crucial genes and intestinal nucleases. Furthermore, it underscores the importance of exploring RNAi-based approaches for pest management.

A Transgenerational Effects of Oil Supplemented Diets on Fruit Flies (Drosophila melanogaster) Progenies

AbstractThe causes of obesity are multifactorial, one of which is the parental diet. Fruit fly (Drosophila melanogaster) has homologous genes with humans and is a potential model organism for research on human diseases. This study aims to examine the transgenerational effects of a modified high-fat diet on the number of progenies, sex ratio, and body weight in eight generations of fruit flies. Four types of diets consisted of different fat compositions were used banana, cornmeal, cornmeal + 3% virgin coconut oil (VCO), and cornmeal + 3% palm oil. Data were analyzed using SPSS with ANOVA and DMRT post hoc analysis. Results showed significant differences (P <0.05) in the number of progenies between the diet without oil and with added oil. A higher number of progenies were found in the diet without oil with an average of 85 flies (banana diet) and 85.04 flies (cornmeal diet) compared to the results in the oil diet with 19 flies (cornmeal + 3% VCO) and 76.67 flies (cornmeal + 3% palm oil)The sex ratio and the body weight were not significantly different between each diet, suggesting that there are other factors involved. There were significant differences between the early and late generations for number of progenies and body weight, but not for sex ratio. The VCO was difficult to mix in the media so palm oil has the potential to be used for further investigations to find a better formula for high-fat diet food sources in an obesity study using fruit flies.AbstrakPenyebab terjadinya obesitas bersifat multifaktorial, salah satunya adalah pola makan orang tua. Lalat buah (Drosophila melanogaster) memiliki gen yang homolog dengan manusia dan merupakan organisme model yang potensial untuk penelitian penyakit manusia. Penelitian ini bertujuan untuk menguji pengaruh transgenerasi pola makan tinggi lemak yang dimodifikasi terhadap jumlah keturunan, rasio jenis kelamin, dan berat badan pada delapan generasi lalat buah. Empat jenis pakan dengan komposisi lemak berbeda digunakan yaitu pisang, tepung jagung, tepung jagung + 3% Virgin coconut oil(VCO) dan tepung jagung + 3% minyak sawit. Data dianalisis menggunakan SPSS dengan analisis post hoc ANOVA dan DMRT. Hasil penelitian menunjukkan perbedaan yang signifikan (P <0,05) pada jumlah keturunan, khususnya antara diet tanpa minyak dengan diet dengan minyak. Jumlah progeni yang lebih banyak terdapat pada diet tanpa minyak dengan rata-rata 85 lalat (diet pisang) dan 85,04 lalat (diet tepung jagung) dibandingkan dengan hasil pada diet minyak dengan 19 lalat (tepung jagung + 3% VCO) dan 76,67 lalat (tepung jagung + 3% minyak sawit). Rasio jenis kelamin dan berat badan tidak berbeda secara signifikan antara masing-masing pola makan, hal ini menunjukkan bahwa ada faktor lain yang terlibat. Terdapat perbedaan yang signifikan antara generasi awal dan akhir dalam hal jumlah keturunan dan berat badan, namun tidak untuk rasio jenis kelamin. VCO sulit untuk dicampurkan dalam media sehingga minyak sawit berpotensi digunakan untuk penelitian lebih lanjut untuk menemukan formula sumber makanan diet tinggi lemak yang lebih baik dalam studi obesitas menggunakan lalat buah.

Modelling time-temperature-dependent mortality of pest flies in cold storage to support the management of trade-related biosecurity risks

AbstractCold treatment with rigorous regulatory oversight is often mandated to manage horticultural trade-related biosecurity threats, such as invasive, cold-sensitive fruit flies (Diptera: Tephritidae). Cold treatment schedules, developed through rigorous laboratory experiments, require a set temperature and duration to ensure at least a probit 8.7 (99.99%) mortality rate, regardless of infestation likelihood. This threshold is costly to demonstrate for each pest and commodity combination and the resultant treatment may be harmful to fruit quality. Moreover, these stringent schedules do not account for cold-induced mortality already occurring in commercial supply chains. We developed a predictive temperature-dependent mortality function using 28 published cold treatment studies of pest fly species to support more flexible and proportionate use of cold treatment. The daily mortality rate was unaffected by the duration of cold exposure (0–20 days). The mortality rate varied primarily by pest species (10 species) and developmental stage (eggs and larval stages), and to a lesser extent by temperature (0–7 °C) and host (13 fruit types). Our model mostly predicted fewer days to meet probit 9.0 mortality compared to empirical results from large-scale studies, suggesting these studies can be overly conservative. By leveraging previous empirical studies, our model enables estimation of temperature-dependent daily mortality for unstudied pest developmental stage host–temperature combinations, which can then be empirically validated through targeted studies. It is hoped these results will shift cold treatment usage from highly regulated, fixed temperature treatments with a target mortality rate requirement to a more flexible approach that accounts for existing commercial supply chain practices and infestation likelihood in produce.

Tissue-specific metabolomic signatures for a doublesex model of reduced sexual dimorphism.

Sex has a major effect on the metabolome. However, we do not yet understand the degree to which these quantitative sex differences in metabolism are associated with anatomical dimorphism and modulated by sex-specific tissues. In the fruit fly, Drosophila melanogaster, knocking out the doublesex (dsx) gene gives rise to adults with intermediate sex characteristics. Here we sought to determine the degree to which this key node in sexual development leads to sex differences in the fly metabolome. We measured 91 metabolites across head, thorax and abdomen in Drosophila, comparing the differences between distinctly sex-dimorphic flies with those of reduced sexual dimorphism: dsx null flies. Notably, in the reduced dimorphism flies, we observed a sex difference in only 1 of 91 metabolites, kynurenate, whereas 51% of metabolites (46/91) were significantly different between wildtype XX and XY flies in at least one tissue, suggesting that dsx plays a major role in sex differences in fly metabolism. Kynurenate was consistently higher in XX flies in both the presence and absence of functioning dsx. We observed tissue-specific consequences of knocking out dsx. Metabolites affected by sex were significantly enriched in branched chain amino acid metabolism and the mTOR pathway. This highlights the importance of considering variation in genes that cause anatomical sexual dimorphism when analyzing sex differences in metabolic profiles and interpreting their biological significance.

Studying Drosophila Larval Behavior in Agarose Channels.

Larvae of the fruit fly Drosophila melanogaster are a popular and tractable model system for studying the development and function of sensorimotor circuits, thanks to the relative numerical simplicity of their nervous system and the wealth of available genetic tools to manipulate the anatomy, activity, and function of specific cell types. Researchers studying the role of a particular gene or cell type in sensorimotor circuit activity or function may wish to observe the effects of an experimental manipulation during behavior in the intact animal. Observing these effects, which may include changes in the intracellular calcium concentration or movement of small numbers of neurons, muscles, etc., typically requires high-spatial-resolution imaging, which poses several difficulties in the freely crawling larva. Freely crawling larvae can move quickly and with changeable heading, making manual or automatic tracking challenging; additionally, they may make three-dimensional movements, such as rearing, that can degrade imaging focus. These challenges are potentially solvable using advanced imaging and algorithmic tracking setups, but cost, space, or development time may be prohibitive. This protocol describes a simple and cost-effective method for placing larvae inside agarose channels, thereby restricting larval crawling to a single dimension and enabling higher-magnification time-series imaging of fluorescently labeled structures during many cycles of locomotion. By using larvae that express fluorescent calcium indicators in cells of interest, researchers can apply this method to study the effects of experimental manipulations on neural or muscular activity during behavior in the intact animal.

Positional Effects of a Fly’s Wing Vein in the Asymmetric Distribution of Hydraulic Resistances

Insect wing vein networks facilitate blood transport with unknown haemodynamic effects on their structures. Fruit flies have the posterior cross vein (PCV) that disrupts the symmetry of the network topology and reduces the total pressure loss during blood transport; however, the impact of its various positions among species has not been examined. This study investigated the haemodynamic effects of this vein with various connecting positions. By analogising venous networks to hydraulic circuits, the flow rates and pressure losses within the veins were derived using Poiseuille’s and Kirchhoff’s laws. The results showed that the total pressure loss decreased for both PCV connections near the wing’s base. In an idealised circuit imitating the network topology, applied high hydraulic resistances as one-sided as those along the edge of the wing, the same pressure loss response as that in the actual network was demonstrated, but not within a symmetric resistance distribution. Therefore, the most proximal PCV minimises the pressure loss within the asymmetric resistance distribution, indicating an evolutionary adaptation to reducing the pressure loss in certain species with this vein near the base. Our findings highlight the possible optimisation of the flies’ wing morphology to maintain the functions of the liquid transport networks and flight devices simultaneously.

Projection of the Potential Global Geographic Distribution of the Solanum Fruit Fly Bactrocera latifrons (Hendel, 1912) (Diptera: Tephritidae) Based on CLIMEX Models

The solanum fruit fly Bactrocera latifrons (Diptera: Tephritidae) is an invasive alien insect that causes huge economic losses to pepper and other solanaceous plant industries. It is mainly distributed in South and Southeast Asia, SW Europe, Western USA, and in some African countries. However, the potential global geographical distribution of B. latifrons is unknown. Therefore, in this study, based on the current (1981–2010) and future (2040–2059) climatic scenarios determined using the CNRM-CM5, Access1.0, GFDL-ESM-2M, and NorESM1-M models, we used a species distribution model (CLIMEX 4.0) to project the potential global geographic distribution of B. latifrons to prevent further invasion and harm. In the current climate scenario, South America (1286.06 × 104 km2), Africa (1435.47 × 104 km2), and Oceania (410.66 × 104 km2) have the largest proportions of suitable land areas for B. latifrons colonization. Under all four future climate models, the global potential suitable area for Bactrocera latifrons is projected to decrease and shift towards higher latitudes. This study provides an important baseline upon which researchers, quarantine personnel, and governments can develop the appropriate control strategies against B. latifrons.

Pharmacology of Aging: Drosophila as a Tool to Validate Drug Targets for Healthy Lifespan.

Finding effective therapies to manage age-related conditions is an emerging public health challenge. Although disease-targeted treatments are important, a preventive approach focused on aging can be more efficient. Pharmacological targeting of aging-related processes can extend lifespan and improve health in animal models. However, drug development and translation are particularly challenging in geroscience. Preclinical studies have survival as a major endpoint for drug screening, which requires years of research in mammalian models. Shorter-lived invertebrates can be exploited to accelerate this process. In particular, the fruit fly Drosophila melanogaster allows the validation of new drug targets using precise genetic tools and proof-of-concept experiments on drugs impacting conserved aging processes. Screening for clinically approved drugs that act on aging-related targets may further accelerate translation and create new tools for aging research. To date, 31 drugs used in clinical practice have been shown to extend the lifespan of flies. Here, we describe recent advances in the pharmacology of aging, focusing on Drosophila as a tool to repurpose these drugs and study age-related processes.

Hierarchical communities in the larval Drosophila connectome: Links to cellular annotations and network topology

One of the longstanding aims of network neuroscience is to link a connectome's topological properties-i.e., features defined from connectivity alone-with an organism's neurobiology. One approach for doing so is to compare connectome properties with annotational maps. This type of analysis is popular at the meso-/macroscale, but is less common at the nano-scale, owing to a paucity of neuron-level connectome data. However, recent methodological advances have made possible the reconstruction of whole-brain connectomes at single-neuron resolution for a select set of organisms. These include the fruit fly, Drosophila melanogaster, and its developing larvae. In addition to fine-scale descriptions of connectivity, these datasets are accompanied by rich annotations. Here, we use a variant of the stochastic blockmodel to detect multilevel communities in the larval Drosophila connectome. We find that communities partition neurons based on function and cell type and that most interact assortatively, reflecting the principle of functional segregation. However, a small number of communities interact nonassortatively, forming form a "rich-club" of interneurons that receive sensory/ascending inputs and deliver outputs along descending pathways. Next, we investigate the role of community structure in shaping communication patterns. We find that polysynaptic signaling follows specific trajectories across modular hierarchies, with interneurons playing a key role in mediating communication routes between modules and hierarchical scales. Our work suggests a relationship between system-level architecture and the biological function and classification of individual neurons. We envision our study as an important step toward bridging the gap between complex systems and neurobiological lines of investigation in brain sciences.

Moringa Reduces Glucose Levels and Alters Wolbachia Abundance in Drosophila melanogaster

Moringa oleifera Lam. (moringa) is a plant native to India, used as a nutritional and medicinal supplement in many cultures around the world. Moringa has been linked to maintaining metabolic homeostasis and is often marketed as a weight loss supplement and a potential remedy for diseases such as diabetes. Here, we investigate how moringa, a ‘superfood’ with predicted protective effects against chronic diseases such as diabetes, influences the nutritional physiology and microbiome composition of the fruit fly Drosophila melanogaster. We administered moringa as a dietary supplement to Drosophila, and quantified key nutritional indices: glucose, triacylglyceride, and protein levels, and fly weight. We showed that dietary moringa supplementation significantly reduced fly glucose levels by up to ~30% and resulted in substantial restructuring of Drosophila microbiota composition, altering both gut and intracellular bacterial populations. The effect of moringa on fly glucose levels is specific because other nutritional indices, namely, triacylglyceride and protein levels and fly weight, were not significantly affected by dietary moringa supplementation. This study highlights the importance of moringa as a modulator of host glucose metabolism.

From computational prediction to experimental validation: Hesperidin's anti-Urolithiatic activity in sodium oxalate-induced urolithiasis models in fruit flies and mice

Kidney stones have been a long-standing health issue, contributing to renal failure, especially in co-morbid patients. There is an increasing interest in exploring natural compounds with anti-urolithiatic properties. Our study utilized in-silico techniques followed by in vivo experiments to evaluate the anti-urolithiatic potential of selected phytoconstituents. Molecular docking studies were conducted on 11 different targets, including inhibitors of kidney stone formation, antioxidant enzymes, and biomarkers of kidney injury, to explore the potential of anti-urolithiatic effects of 38 phytoconstituents from medicinal plants possessing diuretic activity. Further, the anti-urolithiatic activity of the phytoconstituent was evaluated using a sodium oxalate-induced urolithiatic fruit fly and mouse model. Hesperidin emerged as a promising candidate, exhibiting binding interactions with a specific set of 11 target proteins involved in crystal formation with minimal free energy. Hesperidin demonstrated promising anti-urolithiatic potential in mitigating urolithiasis as evidenced by reduced crystal covered area of Malpighian tubules of fruit fly and reduced blood urea nitrogen (BUN), serum creatinine and serum sodium, potassium levels in mice. Moreover, it increased urine volume, preventing crystal deposition, and reduced urine urea nitrogen, creatinine, sodium, and potassium levels, enhancing urine flow and preventing crystal accumulation. Histopathological analysis further supported its efficacy by showing minimal crystal deposition and reduced kidney damage. Hesperidin exhibited superior effectiveness in reducing various serum and urine parameters, making it promising alternatives for urolithiasis management warranting further investigation to determine its safety and optimal dosages in human.

In-vivo toxicological study of cysteamine modified carbon dots derived from Ruellia simplex on fruit fly for potential bioimaging

Modern medicine must shift its paradigm from conventional treatment strategies to theranostics to meet individuals' needs. Carbon dots, as a class of fluorescent materials, provide biocompatible and multifunctional solutions for a wide range of applications including clinical sensing, imaging, and drug delivery. Various studies have focused on their synthesis, photophysical properties, and innoxious nature but their potential biomedical applications for the in-vivo toxicity are yet limited. In this work, previously synthesized C-Dots (CDs) were utilized to determine their effect on the development of Drosophila melanogaster. Simultaneously, the genotoxic potential of CDs was evaluated on specific larval cell types that play important roles in immunological defence as well as growth and development. The gut organ toxicity of both CDs was studied using DAPI and DCFH-DA dyes wherein RS-CDs didn't show significant toxicity to the concentration 500 μg/mL whereas RS-Cys-CDs showed nuclear fragmentation and modest ROS (reactive oxygen species) production. Subsequently, trypan-blue assay, larvae crawling assay, touch sensitivity, adult phenotype, and survivability assay were performed. The trypan-blue assay shows the non-toxic nature of both CDs even at the concentration of 500 μg/mL. The high concentrations of RS-Cys-CD (500 μg/mL) were further associated with the alteration in touch behaviour and decrease in pupa hatching. In-vivo and ex-vivo fluorescence assessment of both the CDs exhibit bright fluorescence in green and red channels upon excitation at 485 and 577 nm respectively. The prominent imaging results from RS-Cys-CDs highlight the positive impact of surface modification.

Biological Management of Bactrocera dorsalis (Oriental fruit fly) through Enzymatic Activity of Beauveria bassiana

Beauveria bassiana is a viable option for the biocontrol of numerous significant pest insects. Fungal spores adhere to the cuticle after invading the host body. One of the groups of enzymes that entomopathogenic fungi have that guarantees good penetration is cuticle destroying enzyme. A recent study found that it is possible to extract the crude cuticle-degrading enzymes from B. bassiana and combine them with mycelium to make the organism more harmful for its host. With a pH of 8.6, the molecular weights of the samples (enzymes) were calculated in kDa for both the resolving gel (12%), and the stacking gel (4%). The result showed that, unlike the traditional key, discrete bands with different sizes appeared after the gel was stained and distaining. The proteases, lipases, and chitinase were confirmed by the bands detected at 19, 50, 25, 32, and 34.25 kDa, respectively. The raw enzymes that were isolated were applied in quantities of 5, 10, 15, 20, and 25µL to larvae, pupae, and adults. At 25µL/mL, the death rates for larvae and adults were found to be 78.50±2.10% and 80±2.15%, respectively. The mortality was 13.33±1.92% at lower dosages (5µL/mL), with control coming in second. The treated insects showed a low proportion of adult emergence (10±2.63%) from pupae, while the untreated group of insects showed a greater percentage (65.0±5.77%) of adult emergence. The outcome demonstrated that concentration affected both adult emergence from pupae and mortality. Consequently, the addition of CDE to B. bassiana mycelium increased its pathogenicity against various phases of Bactrocera dorsalis life cycle.

Characterization of increased mortality of Drosophila melanogaster exposed to sucrose-fermenting yeast

Adult fruit flies are strongly attracted to odors emitted by the microbial fermentation of sugars in fruits. Such microbes, particularly yeasts, also serve as an essential nutritional source for fruit flies and influence their reproduction and fecundity. Despite being known as natural symbionts, it was previously observed that sucrose-fermenting Saccharomyces cerevisiae can be lethal to Drosophila melanogaster. This study characterizes the conditions that affect the lethality of S. cerevisiae in fruit flies. We showed that the insecticidal activity of yeast was equal in five tested S. cerevisiae strains. Another yeast, Pichia anomala, killed fruit flies, although to a lesser degree than S. cerevisiae. Higher concentrations of yeast resulted in faster killing of fruit flies, although the killing rate was capped at two days of continuous exposure. Both sexes were similarly sensitive to yeast at 30, whereas males were less sensitive to yeast at 25 degrees Celsius. Higher sucrose amounts in food slightly decreased the sensitivity of male but not female flies to yeast. This study characterizes a relatively uncharted side of the intricate interaction between fruit flies and yeast and highlights the possibility for manipulation aimed at mitigating the agricultural impact of these pests.

Local and landscape constraints of adult population of Anastrepha obliqua (Diptera: Tephritidae) in mango orchards

Introduction: The West Indian fruit fly, Anastrepha obliqua (Macquart), is one of the most economically important pests of mangoes in Mexico and the Neotropics. Objective: To analyze adult population patterns of A. obliqua and their relation to local and landscape factors. Methods: We selected 11 “Manila” mango orchards along the middle part of La Antigua River, which were characterized to determine their biophysical structure and landscape configuration considering their distance to six different land uses/land covers. Anastrepha obliqua population was estimated by collecting adult flies in colorless polyethylene plastic bottle traps baited with a protein for three weeks in June 2022. Results: A total of 1 869 adults of A. obliqua were trapped, of which 75 % were females and 25 % were males. Abundance varied from 68 to 490 adult flies per orchard, while capture frequency from 0.36 to 1.8 flies/trap/day. Abundance increased in highly shaded orchards, and capture frequency decreased in orchards with highly soil compaction. Abundance and the frequency of capture increased in orchards near isolated trees of Spondias spp. and decreased in orchards near sugarcane plantations. Shade management in mango orchards may be used as an effective strategy to promote biotic interactions to naturally regulate A. obliqua populations, meanwhile, soil compaction represents a limiting ecological condition, which might severely impact fruit fly larvae survival. Conclusions: Adult population of A. obliqua depends on several local and landscape factors because they indicate resource availability and ecological conditions. These findings could be considered for control strategies in the integrated management of this pest to promote protection and improve the fruit quality of mango crop.

Larvae of Zeugodacus cucurbitae (Melon fruit fly) grown on varying natural food contents experience significant effect on their weight and biochemical parameters

Larvae of Zeugodacus cucurbitae (Melon fruit fly) grown on varying natural food contents experience significant effect on their weight and biochemical parameters

Drosophila are hosts to the first described parasitoid wasp of adult flies

Parasitoid wasps are exceptionally diverse and use specialized adaptations capable of manipulating the physiology and behaviour of host organisms1. In more than two centuries since the first records of Drosophila-parasitizing wasps, nearly 200 described and provisional parasitoid species of drosophilids have been identified2. These include endoparasitoids and ectoparasitoids, as well as species attacking larval and pupal hosts3. Despite a deep history of research attention and remarkable biodiversity, a wasp species that attacks and develops inside the adult stage of a fly host has not been described previously. Here we report the discovery of a wasp species that infects the adult stage of fruit flies in the genus Drosophila, including one of the most deeply studied model organisms in biology, Drosophila melanogaster. Notably, this wasp can be easily collected from backyard fly baits and has a broad geographic distribution throughout the eastern USA. We document its life history and unique host interactions, including egg-laying into and larval emergence from adult flies, and provide protocols to raise wasps from wild-caught host flies. Our results emphasize the need for ongoing research investment in insect biodiversity and systematics. As parasitoid research continues to uncover unusual biology and supports fundamental mechanistic insights into immunity4, metabolism5, ecology6, evolution7–9 and behaviour10–12, we anticipate that this wasp’s association with the laboratory model organism, D. melanogaster, will provide new research opportunities across the life sciences.

Chitosan-coated probiotic nanoparticles mitigate acrylamide-induced toxicity in the Drosophila model

Acrylamide (ACR) with its extensive industrial applications is a classified occupational hazard toxin and carcinogenic compound. Its formation in fried potatoes, red meat and coffee during high-temperature cooking is a cause for consideration. The fabrication of chitosan-coated probiotic nanoparticles (CSP NPs) aims to enhance the bioavailability of probiotics in the gut, thereby improving their efficacy against ACR-induced toxicity in Drosophila melanogaster. Nanoencapsulation, a vital domain of the medical nanotechnology field plays a key role in targeted drug delivery, bioavailability, multi-drug load delivery systems and synergistic treatment options. Our study exploited the nanoencapsulation technology to coat Lactobacillus fermentum (probiotic) with chitosan (prebiotic), both with substantial immunomodulatory effects, to ensure the stability and sustained release of microbial load and its secondary metabolites in the gut. The combination of pre-and probiotic components, called synbiotic formulations establishes the correlation between the gut microbiota and the overall well-being of an organism. Our study aimed to develop a potent synbiotic to alleviate the impacts of heat-processed dietary toxins that significantly influence behaviour, development, and survival. Our synbiotic co-treatment with ACR in fruit flies normalised neuro-behavioural, survival, redox status, and restored ovarian mitochondrial activity, contrasting with several physiological deficits observed in the ACR-treated model.

Connectome-constrained networks predict neural activity across the fly visual system

We can now measure the connectivity of every neuron in a neural circuit1–9, but we cannot measure other biological details, including the dynamical characteristics of each neuron. The degree to which measurements of connectivity alone can inform the understanding of neural computation is an open question10. Here we show that with experimental measurements of only the connectivity of a biological neural network, we can predict the neural activity underlying a specified neural computation. We constructed a model neural network with the experimentally determined connectivity for 64 cell types in the motion pathways of the fruit fly optic lobe1–5 but with unknown parameters for the single-neuron and single-synapse properties. We then optimized the values of these unknown parameters using techniques from deep learning11, to allow the model network to detect visual motion12. Our mechanistic model makes detailed, experimentally testable predictions for each neuron in the connectome. We found that model predictions agreed with experimental measurements of neural activity across 26 studies. Our work demonstrates a strategy for generating detailed hypotheses about the mechanisms of neural circuit function from connectivity measurements. We show that this strategy is more likely to be successful when neurons are sparsely connected—a universally observed feature of biological neural networks across species and brain regions.

The primacy model and the structure of olfactory space.

Understanding sensory processing relies on the establishment of a consistent relationship between the stimulus space, its neural representation, and perceptual quality. In olfaction, the difficulty in establishing these links lies partly in the complexity of the underlying odor input space and perceptual responses. Based on the recently proposed primacy model for concentration invariant odor identity representation and a few assumptions, we have developed a theoretical framework for mapping the odor input space to the response properties of olfactory receptors. We analyze a geometrical structure containing odor representations in a multidimensional space of receptor affinities and describe its low-dimensional implementation, the primacy hull. We propose the implications of the primacy hull for the structure of feedforward connectivity in early olfactory networks. We test the predictions of our theory by comparing the existing receptor-ligand affinity and connectivity data obtained in the fruit fly olfactory system. We find that the Kenyon cells of the insect mushroom body integrate inputs from the high-affinity (primacy) sets of olfactory receptors in agreement with the primacy theory.