Biology subjects

Ribeiro, C.

Publications and source records attributed to Ribeiro, C..

At least 19 recordsLinked to original sources

bioRxiv2026

In Vitro Fertilization using Magnetotactic Sperm Cells

In vitro fertilization (IVF) is essential for many couples facing infertility, e.g. in cases of low sperm count (oligospermia), where natural fertilization is unlikely. Medical microrobotics, making use of microscopic devices designed to perform targeted tasks inside the body under imaging guidance and controlled actuation, represents a promising strategy to guide sperm cells toward the oocyte. This approach may significantly reduce the time, invasiveness, and patient burden of conventional IVF, with long-term potential for in vivo assisted reproduction. Here, we report the first successful in vitro fertilization (IVF) using magnetically functionalized spermatozoa, termed magnetotactic sperm cells (MSCs), as a step toward in vivo microrobotic guidance of sperm cells for targeted artificial insemination. We present a protocol for the preparation of MSCs for their use in IVF, resulting in samples largely free of non-functionalized sperm cells (99.69% purity). We systematically evaluate the effect of particle functionalization on sperm health, including acrosome integrity, DNA fragmentation, mitochondrial membrane potential, oxidative stress, and epithelial interactions, and observe no adverse effects. Notably, MSCs showed improved mitochondrial membrane integrity compared to the control samples after two hours of incubation. Using MSCs, we successfully performed complete IVF cycles that resulted in embryos developing to the blastocyst stage at a comparable rate as non-functionalized sperm cells of the same concentration. Lower concentrations of non-functionalized sperm cells (comparable to those remaining in the MSC sample after purification) did not result in any development of embryos to blastocysts. To facilitate manipulation and translation, we implemented automated image-based recognition, magnetic manipulation, and pre-clustering routines that increased guidance efficiency and are compatible with standard IVF workflows. Together, these results demonstrate that magnetic functionalization can be applied without compromising key sperm quality metrics and can enable directed sperm guidance for assisted oocyte fertilization. This work provides a practical framework for integrating microrobotic sperm manipulation into assisted-reproduction workflows and supports further development toward automated in vitro and eventual in vivo applications.

bioengineering↗

bioRxiv2026

Ovary-Derived Signals Align Protein Appetite with Oogenesis

Maintaining organismal homeostasis requires mechanisms that coordinate the metabolic needs of individual organs with whole animal nutrient intake. Although nutrient sensors and central pathways regulating hunger have been extensively characterized, how peripheral organ physiology influences nutrient specific appetites remains poorly understood. Here, we identify a previously unrecognized signalling axis, originated in the ovary, that modulates yeast appetite in Drosophila melanogaster. Through a targeted germline RNAi screen, we find that specific perturbations in oogenesis consistently and selectively increase yeast appetite. The manipulations increasing yeast appetite disrupt oogenesis progression, producing a shared signature of increased vitellogenic follicle accumulation and reduced number of mature (stage14) oocytes. This shift is accompanied by decreased expression of the relaxin-like hormone Dilp8, and loss of Dilp8 recapitulates the feeding phenotype. We show that this ovarian regulation of nutrient specific appetite is independent of amino acid state but requires mating, indicating integration with Sex Peptide-mediated reproductive activation. Together, our findings uncover a novel mechanism that couples oogenesis progression to nutrient selection, emphasizing the importance of the ovary as an active regulator of whole organism nutritional decisions. This work provides a conceptual framework for how reproductive tissues communicate their physiological demands to other organs and raises the possibility that analogous ovary-derived signals may shape nutrient specific appetite and metabolic states in other animals. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=163 SRC="FIGDIR/small/711327v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@153c136org.highwire.dtl.DTLVardef@1b1e6dcorg.highwire.dtl.DTLVardef@abaab3org.highwire.dtl.DTLVardef@53f725_HPS_FORMAT_FIGEXP M_FIG C_FIG Created in BioRender. Francisco, A. (2026) https://BioRender.com/pwalhtl

physiology↗

bioRxiv2025

Glutamine antagonism suppresses tumor growth in adrenocortical carcinoma through inhibition of de novo nucleotide biosynthesis

Dysregulation of cellular metabolism is a hallmark of cancer, which remains poorly understood in adrenocortical carcinoma (ACC). Here, we dissected ACC metabolism by integrating transcriptional profiling from human and mouse ACC, targeted tissue metabolomics from a mouse ACC model, and untargeted serum metabolomics from a large patient cohort, providing cross-species validation of metabolic rewiring in ACC. This study revealed global metabolic dysregulation, involving glutamine-dependent pathways such as non-essential amino-acid and hexosamine biosynthesis, nucleotide metabolism, and glutathione biosynthesis, suggesting glutamine catabolism is a critical metabolic vulnerability in ACC. Treatment with glutamine antagonists 6-Diazo-5-Oxo-L-Norleucine (DON) and JHU-083 elicited robust anti-tumor responses. Mechanistic studies revealed DONs anti-tumor effect was primarily driven by selective inhibition of glutamine-fueled de novo nucleotide biosynthesis. Additionally, DON led to DNA damage, which yielded potent synergism with inhibition of the DNA damage response pathway. Collectively, this work highlights glutamine metabolism as a central metabolic dependency and therapeutic target in ACC. HighlightsO_LIMouse and human ACC share conserved transcriptional-metabolic programs, revealing Gln metabolism as a central, targetable vulnerability. C_LIO_LITargeted tissue metabolomic analysis in a mouse model of ACC validates dysregulation in Gln-dependent metabolic pathways. C_LIO_LITargeting of Gln metabolism with JHU-083 (6-diazo-5-oxo-L-norleucine (DON) pro-drug) achieves marked inhibition of tumor growth in vivo. C_LIO_LIHigh expression of Gln-metabolizing genes mediating de novo nucleotide biosynthesis is associated with poor prognosis in ACC. C_LIO_LIDON drives nucleotide depletion and DNA damage, leading to potent synergy with inhibition of the DNA damage response. C_LIO_LIUntargeted serum metabolomic analysis in a large cohort of patients with adrenal tumors demonstrates dysregulation of Gln and nucleotide metabolism in ACC. C_LI

cancer biology↗

bioRxiv2025

Magnetically Controlled Microrobots for In Vivo Non-Invasive Embryo Transfer

Infertility affects millions worldwide and is often linked to factors such as poor sperm quality and female reproductive organ disorders. Despite significant advancements in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), implantation rates remain low, ranging from 17 to 21% after three days of incubation, mainly due to stress, lifestyle factors, and uterine conditions. Extended embryo culture techniques have shown promise in improving pregnancy rates. However, the availability of high-quality blastocysts remains a major challenge. Intrafallopian transfer techniques, such as gamete/zygote intrafallopian transfer (GIFT/ZIFT), were introduced to improve fertilization and early embryo development, particularly for patients with repeated embryo implantation failure (10-30% of assisted reproduction technology (ART) cases, particularly in women >35). However, these methods have declined due to advancements in IVF and the variability in laparoscopy procedures used for GIFT/ZIFT. To address these challenges, we propose a non-invasive microrobotic embryo transfer ({micro}ET) technique using remotely controlled microcarriers comparable in size to embryos. We demonstrate the capabilities of magnetically actuated spiral microrobots, fabricated using laser direct writing for capturing, transporting, and releasing embryos into murine uteri. Additionally, we characterize their motion performance and implement image-guided closed-loop control and dual ultrasound (US)/photoacoustic (PA) tracking for deep-tissue interventions. Recognizing the importance of clinical translation, we present preliminary studies on gelatin-based microrobots, a biodegradable alternative, and explore endometrial remodeling after the in vivo transfer of microrobots carrying embryo-like structures. Our findings show that these microrobots can effectively transport embryos, support their development, and enable minimally invasive delivery, providing a more natural, targeted, and non-invasive strategy for in vivo assisted reproduction. One-Sentence SummaryWe propose a non-invasive {micro}ET technique using magnetically actuated microcarriers to improve embryo cargo-delivery in assisted reproduction, addressing challenges in infertility treatments by enabling precise, image-guided embryo delivery with minimal invasiveness.

bioengineering↗

bioRxiv2025

The improved auxin signalling via entire mutation enhances aluminium tolerance in tomato

Acidic soils limit food production in many developing countries by promoting the solubilization of aluminium (Al) cations. Consequently, roots absorb this metal from soil solution, arresting their growth while reducing water and nutrient uptake. To mitigate the impacts of Al, plants rewire their metabolism and growth, with diverse mechanisms in this process shaped by changes in auxin signalling. Here, we present a comprehensive study on the significance of auxin signalling for Al tolerance. We used tomato mutants with reduced (diageotropica, dgt) and increased (entire) auxin sensitivity to assess the regulation of growth and metabolism in plants coping with Al toxicity. Our results indicated a reduced Al tolerance in the dgt mutant, whereas entire was able to tolerate toxic levels of Al. This contrast can be explained by a differential accumulation of reactive oxygen species (ROS) in the root transition zone, where dgt exhibited more differentiated cells, making the pericycle evident. In contrast, entire showed only slight alterations in the transition zone, with root meristematic cells maintaining a reduced level of cell differentiation, which can be associated with sustained growth under toxic Al levels. These differences were followed by alterations in metabolites related to Al sensitivity in the roots of dgt plants, whereas the entire mutant exhibited only slight metabolic changes. Collectively, our results suggest that genetic modifications to regulate auxin perception have the potential to increase Al tolerance in crops.

plant biology↗

bioRxiv2025

From Sensory Detection to Motor Action: The Comprehensive Drosophila Taste-Feeding Connectome

Gustatory systems drive critical survival behaviors such as feeding, foraging, and social interactions. However, gustation remains one of the least mapped sensory modalities at the connectome level. Here, we present the first complete wiring diagram of the male Drosophila adult gustatory system, comprehensively reconstructing gustatory receptor neurons (GRNs) from peripheral organs in a contiguous electron microscopy volume spanning brain, cervical connective, and ventral nerve cord. Integrating this with existing datasets, we generated a pan-CNS, cross-sex connectome that reveals GRN diversity through connectivity-based clustering, molecular identity mapping, and sexual dimorphism analysis. We mapped all feeding motor neurons and traced complete sensory-to-motor pathways to feeding, foraging, endocrine, and social behavior circuits. The emerging circuit architectures reveal distinct circuits for nutrient assessment, motor control, neuroendocrine regulation, and courtship. This work defines the gustatory systems organization at synaptic resolution and provides a framework for understanding how internal states modulate sensory-driven decisions across behavioral contexts.

neuroscience↗

bioRxiv2025

Connectomics Reveals a Feed-Forward Swallowing Circuit Driving Protein Appetite

Nutrient state shapes not only what animals eat, but how they eat it. We lack circuit-level mechanisms explaining how gustatory and internal state information regulates feeding at the motor control level. In Drosophila, protein deprivation prolongs protein-specific feeding bursts, yet the detailed motor mechanisms underlying this change remain unknown. Using EM connectomics, we identified a feed-forward pathway from proteinsensitive gustatory receptor neurons to swallowing motor neurons. At its core is the Sustain neuron, which coordinates multiple swallowing motor neurons to move food efficiently through the cibarium and pharynx. This nutrient-dependent facilitation of swallowing sustains long feeding bursts, directly linking internal state to the temporal structure of the feeding motor program. Our findings reveal how a dedicated sensorimotor circuit translates physiological need into precise motor control to drive nutrient-specific feeding appetite and highlights the power of combining EM connectomics with experimental circuit dissection.

neuroscience↗

bioRxiv2025

Mechanistic dissection of Candidatus Liberibacter Triggered Chronic Immune Disease

Immunity is generally considered critical for plant health against pathogen infection. Citrus Huanglongbing (HLB) caused by the phloem colonizing bacterial pathogen Candidatus Liberibacter asiaticus (CLas) was suggested to be a pathogen triggered chronic immune disease. However, the genetic evidence and mechanistic understanding for such a disease model is lacking. Here, we show CLas triggers phloem cell death, reactive oxygen species (ROS) production and callose deposition in photosynthesis tissues, but little or none in non-photosynthesis tissues of citrus. We further demonstrate that CLas triggers ROS production in chloroplasts. Overexpression of flavodoxin (Fld), an electron shuttle, in chloroplasts reduced ROS production, cell death and HLB symptoms, but not phloem callose deposition induced by CLas. Knockout, silencing, and overexpression of phloem callose synthase genes CsCalS7a, CsCalS7b, or CsCalS7c demonstrated that phloem callose deposition also caused phloem cell death. Trunk injection with 2-deoxy-d-glucose, a callose deposition inhibitor, reduced fruit drop and increased fruit yield of HLB symptomatic trees in field trials. Using tomato-Ca. L. psyllaurous (Lpsy) as a model, knockout of Eds1 and Pad4 but not RbohB, Bik1 and Sobir1 abolished ROS production, phloem callose deposition, cell death and disease damages caused by Lpsy. This study provides genetic evidence for Ca. Liberibacter-triggered immune disease and reveals that tuning plant immune responses converts Ca. Liberibacter into a benign endophyte, providing a promising strategy for precision breeding to enhance resistance/tolerance against HLB.

plant biology↗

bioRxiv2025

Oxytocin Receptor Expression and Activation in Parasympathetic Brainstem Cardiac Vagal Neurons

Autonomic imbalance, particularly reduced activity from brainstem parasympathetic cardiac vagal neurons (CVNs) is a major characteristic of many cardiorespiratory diseases. Therapeutic approaches to selectively increase CVN activity have been limited by lack of identified selective translational targets. Recent work has shown that there is an important excitatory synaptic pathway from oxytocin (OXT) neurons in the paraventricular nucleus of the hypothalamus (PVN) to brainstem CVNs, and that OXT could provide a key selective excitation of CVNs. In clinical studies, intranasal OXT increases parasympathetic cardiac activity, autonomic balance, and reduces obstructive event durations and oxygen desaturations in obstructive sleep apnea patients. However, the mechanisms by which activation of hypothalamic OXT neurons, or intranasal OXT, increases brainstem parasympathetic cardiac activity is poorly understood. CVNs are located in two cholinergic brainstem nuclei: the nucleus ambiguus (NA) and dorsal motor nucleus of the vagus (DMNX). In this study we characterize the co-localization of OXT receptors in CVNs (OXTR), as well as non-CVN cholinergic neurons, located in the NA and DMNX nuclei. Selective chemogenetic excitation of OXTR+ CVNs was performed by expressing DREADDs with a combination of Cre and flp dependent viruses. We found that OXT receptors are highly expressed in CVNs in the DMNX and OXT increases DMNX CVN activity, but the receptors and responses are absent in CVNs in the NA. Selective chemogenetic activation of OXTR+ CVNs in the DMNX evoked a rapid and sustained bradycardia.

neuroscience↗

bioRxiv2024

Plant recruitment six years after the Samarcos tailings-dam disaster: Impacts on species richness and plant growth

One of the greatest tragedies in Brazilian mining history occurred in November 2015 in Mariana, Minas Gerais state, when a dam from the mining company Samarco was breached. Millions of mine tailings from this upstream embankment were dumped over the Doce River basin, impacting an area of approximately 1469 ha of riparian vegetation. Our objective was to experimentally investigate whether plant recruitment and establishment are impaired in areas affected by tailings six years after the deposition. To achieve this goal, in 2021 we compared soil chemical properties between affected and unaffected areas, performed a soil seed bank experiment in controlled conditions, and conducted a greenhouse growth experiment using the two most abundant plant species. Affected soils presented lower fertility and organic matter content. At the same time, the mean abundance and richness of emerging plants did not differ between soils. Still, affected areas exhibited approximately 35% lower accumulated species richness (gamma diversity) than unaffected ones. The three most abundant species in both areas represented 34% of the individuals, being Marsypianthes chamaedrys (Vahl) Kuntze, Ludwigia octovalvis (Jacq.) P.H. Raven and Ageratum conyzoides L. In the growth experiment, plants growing in affected soils presented reduced height and stem diameter increment (L. octovalvis) or allocated fewer resources to root production than aerial parts (M. chamaedrys), potentially in response to soil infertility and density. Even after six years, our results showed that tailings- affected areas continue to experience negative impacts on plant recruitment, highlighting its adverse effects on ecosystem functions and services.

ecology↗

bioRxiv2024

Predicting Mouse Lifespan-Extending Chemical Compounds with Machine Learning

Pharmacological interventions targeting the biological processes of ageing hold significant potential to extend healthspan and promote longevity. This, to our knowledge, is the first study that uses Machine Learning models trained specifically on mouse lifespan data (from DrugAge) to predict lifespan-extending compounds. The use of mammalian data significantly elevates translational relevance compared to previously available models trained predominately on C. elegans data. Our most successful Random Forest classifiers were trained on direct drug-target annotations, including Gene Ontology, UniProt Keywords, pathways (KEGG, Reactome, Wiki) and protein domains (InterPro), whereas models trained on gene expression (LINCS) and chemical substructures (PubChem) underperformed. Models trained on male datasets performed better than those trained on mixed-sex and female datasets, with the latter suffering from severe class imbalance due to much fewer positive-class instances. Notably, features related to G-protein coupled receptors, especially receptors for neurotransmitters, metabolic hormones and sex hormones, were identified as strong predictors of lifespan extension. We used ensemble classifiers comprised of top models to screen compounds from DrugBank, highlighting novel candidates for longevity studies. Major clusters of compounds with the highest predicted longevity-promoting effects target IGF1 and insulin receptors, beta adrenergic receptors, carbonic anhydrases, dopamine and serotonin receptors, voltage-gated potassium and calcium channels, sodium-dependent dopamine, serotonin and noradrenalin transporters, muscarinic acetylcholine receptors and adenosine receptors. We tested 22 predicted compounds in C. elegans and found that 6 of them significantly extended median lifespan: dihydroergotamine, mianserin, bromocriptine, voxtalisib, bms-754807 and solifenacine. We have also created a public web server with our top performing classifier ensembles: https://www.cs.kent.ac.uk/projects/lodprime/ Our study not only provides an important contribution to the longevity pharmacology field but also informs research on the fundamental mechanisms of ageing.

bioinformatics↗

bioRxiv2024

Evolution of taste processing shifts dietary preference

Food choice is an important driver of speciation and invasion of novel ecological niches. However, we know little about the mechanisms leading to changes in dietary preference. Here, we use the three closely-related species Drosophila sechellia, D. simulans and D. melanogaster to study taste circuit and food choice evolution. D. sechellia, a host specialist, feeds exclusively on a single fruit (Morinda citrifolia, noni) - the latter two are generalists living on various substrates. Using quantitative feeding assays, we recapitulate the preference for noni in D. sechellia and detect conserved sweet but altered bitter sensitivity via calcium imaging in peripheral taste neurons. Noni surprisingly activates bitter sensing neurons more strongly in D. sechellia due to a small deletion in one single gustatory receptor. Using volumetric calcium imaging in the ventral brain, we show that instead of peripheral physiology, species-specific processing of noni and sugar signals in sensorimotor circuits recapitulates differences in dietary preference. Our data support that peripheral receptor changes alone cannot explain altered food choice but rather modifications in how sensory information is transformed into feeding motor commands.

neuroscience↗

bioRxiv2024

Non-canonical Wnt signaling triggered by WNT2B drives adrenal aldosterone production

The steroid hormone aldosterone, produced by the zona glomerulosa (zG) of the adrenal gland, is a master regulator of plasma electrolytes and blood pressure. While aldosterone control by the renin-angiotensin system is well understood, other key regulatory factors have remained elusive. Here, we replicated a prior association between a non-coding variant in WNT2B and an increased risk of primary aldosteronism, a prevalent and debilitating disease caused by excessive aldosterone production. We further show that in both mice and humans, WNT2B is expressed in the mesenchymal capsule surrounding the adrenal cortex, in close proximity to the zG. Global loss of Wnt2b in the mouse results in a dysmorphic and hypocellular zG, with impaired aldosterone production. Similarly, humans harboring WNT2B loss-of-function mutations develop a novel form of Familial Hyperreninemic Hypoaldosteronism, designated here as Type 4. Additionally, we demonstrate that WNT2B signals by activating the non-canonical Wnt/planar cell polarity pathway. Our findings identify WNT2B as a key regulator of zG function and aldosterone production with important clinical implications. HighlightsO_LIWNT2B variant is associated with increased risk for primary aldosteronism C_LIO_LIWnt2b knock-out mice show defects in adrenal morphology C_LIO_LIWnt2b knock-out mice have hyperreninemic hypoaldosteronism C_LIO_LIWNT2B activates non-canonical Wnt/planar cell polarity signaling C_LIO_LIWNT2B deficiency causes a new form of familial hyperreninemic hypoaldosteronism C_LI

genetics↗

bioRxiv2024

Dlk1 is a novel adrenocortical stem/progenitor cell marker that predicts malignancy in adrenocortical carcinoma

Disruption of processes involved in tissue development and homeostatic self-renewal is increasingly implicated in cancer initiation, progression, and recurrence. The adrenal cortex is a dynamic tissue that undergoes life-long turnover. Here, using genetic fate mapping and murine adrenocortical carcinoma (ACC) models, we have identified a population of adrenocortical stem cells that express delta-like non-canonical Notch ligand 1 (DLK1). These cells are active during development, near dormant postnatally but are re-expressed in ACC. In a study of over 200 human ACC samples, we have shown DLK1 expression is ubiquitous and is an independent prognostic marker of recurrence-free survival. Paradoxically, despite its progenitor role, spatial transcriptomic analysis has identified DLK1 expressing cell populations to have increased steroidogenic potential in human ACC, a finding also observed in four human and one murine ACC cell lines. Finally, the cleavable DLK1 ectodomain is measurable in patients serum and can discriminate between ACC and other adrenal pathologies with high sensitivity and specificity to aid in diagnosis and follow-up of ACC patients. These data demonstrate a prognostic role for DLK1 in ACC, detail its hierarchical expression in homeostasis and oncogenic transformation and propose a role for its use as a biomarker in this malignancy. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=160 SRC="FIGDIR/small/609117v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@12aba74org.highwire.dtl.DTLVardef@374daaorg.highwire.dtl.DTLVardef@cbdc37org.highwire.dtl.DTLVardef@1e6aeac_HPS_FORMAT_FIGEXP M_FIG C_FIG Statement of significanceThis study presents DLK1 as a novel biomarker in ACC with opportunities for use in the diagnosis, prognosis and longitudinal follow up of patients. DLK1, a marker of adrenocortical stem cells, is re-expressed in ACC, is measurable in patients serum and is associated with increased malignancy.

cancer biology↗

bioRxiv2024

Lack of Single Amino Acids Transcriptionally Remodels Sensory Systems to Enhance the Intake of Protein and Microbiota

Adequate intake of dietary essential amino acids (eAAs) is vital for protein synthesis and metabolism. Any single eAA deprivation is sufficient to increase protein intake in Drosophila melanogaster. How such nutritional "needs" are transformed into behavioral "wants" remains poorly understood. We derived transcriptomes from the heads of flies deprived of individual eAAs to identify mechanisms by which this is achieved. We found that, while specific eAA deprivations have unique effects on gene expression, a large set of changes are shared across deprivations. We show that Or92a upregulation upon eAA deprivation increases the exploitation of yeast, the main protein source of flies. Furthermore, Ir76a upregulation was crucial for feeding on Lactobacillus, a gut bacterium that ameliorates the fitness of eAA-deprived flies. Our work uncovers common and unique transcriptional changes induced by individual eAA deprivations in an animal and reveals novel mechanisms underlying the organisms behavioral and physiological response to eAA challenges.

neuroscience↗

bioRxiv2024

Exploration and exploitation are flexibly balanced during local search in flies

After finding food, a foraging animal must decide whether to continue feeding, or to explore the environment for potentially better options. One strategy to negotiate this tradeoff is to perform local searches around the food but repeatedly return to feed. We studied this behavior in flies and used genetic tools to uncover the underlying mechanisms. Over time, flies gradually expand their search, shifting from primarily exploiting food sources to exploring the environment, a change that is likely driven by increases in satiety. We found that flies search patterns preserve these dynamics even as the overall scale of the search is modulated by starvation-induced changes in metabolic state. In contrast, search induced by optogenetic activation of sugar sensing neurons does not show these dynamics. We asked what navigational strategies underlie local search. Using a generative model, we found that a change in locomotor pattern after food consumption could account for repeated returns to the food, but failed to capture relatively direct, long return trajectories. Alternative strategies, such as path integration or sensory taxis could allow flies to return from larger distances. We tested this by individually silencing the flys head direction system, olfaction and hygrosensation, and found that the only substantial effect was from perturbing hygrosensation, which reduced the number of long exploratory trips. Our study illustrates that local search is composed of multiple behavioral features that evolve over time based on both internal and external factors, providing a path towards uncovering the underlying neural mechanisms.

neuroscience↗

bioRxiv2023

A neuronal substrate for translating nutrient state and resource density estimations into foraging decisions

Foraging animals must balance the costs of exploring their surroundings with the potential benefits of finding nutritional resources. Each time an animal encounters a food source it must decide whether to initiate feeding or continue searching for potentially better options. Experimental evidence and patch foraging models predict that this decision depends on both nutritional state and the density of available resources in the environment. How the brain integrates such internal and external states to adapt the so-called exploration-exploitation trade-off remains poorly understood. We use video-based tracking to show that Drosophila regulates the decision to engage with food patches based on nutritional state and travel time between food patches, the latter being a measure of food patch density in the environment. To uncover the neuronal basis of this decision process, we performed a neurogenetic silencing screen of more than 400 genetic driver lines with sparse expression patterns in the fly brain. We identified a population of neurons in the central complex that acts as a key regulator of the decision to engage with a food patch. We show that manipulating the activity of these neurons alters the probability to engage, that their activity is modulated by the protein state of the animal, and that silencing these neurons perturbs the ability of the animal to adjust foraging decisions to the flys travel time between food patches. Taken together, our results reveal a neuronal substrate that integrates nutritional state and patch density information to control a specific foraging decision, and therefore provide an important step towards a mechanistic explanation of the cognitive computations that resolve complex cost-benefit trade-offs.

neuroscience↗

bioRxiv2022

marmite defines a novel conserved neuropeptide family mediating nutritional homeostasis

Neuropeptides play a key role in regulating physiology and behavior, including feeding. While animals modify their food choices to respond to the lack of specific nutrients, the mechanisms mediating nutrient-specific appetites remain unclear. Here, we identified marmite (mmt), a previously uncharacterized Drosophila melanogaster gene encoding a secreted peptide that controls feeding decisions. We show that both mmt mutants and neuronal knockdown of mmt specifically increased the intake of proteinaceous food, whereas neuronal mmt overexpression reduced protein appetite. mmt expression is also higher in animals maintained on amino acid rich food, suggesting that mmt encodes a protein-specific satiety signal. Mmt is expressed in a small number of neurons in the adult nervous system, with a single pair of neurons modulating protein appetite. Finally, sequence and phylogenetic analysis showed that mmt is part of an ancient and conserved family of neuropeptides, including the poorly understood vertebrate neuropeptides B and W genes. Functional experiments showed that mmt and vertebrate NPB and NPW modulate food intake in both flies and mice. Therefore, we discovered an ancient family of neuropeptides involved in controlling feeding across phyla.

neuroscience↗