Biology subjects

Yapici, N.

Publications and source records attributed to Yapici, N..

11 recordsLinked to original sources

bioRxiv2026

Cross-Kingdom Control: Yeast Prion Protein Modulates Host Physiology in Drosophila

Prions, once mainly studied for their pathogenic roles, are now gaining recognition as adaptive elements in microbial physiology. Over one-third of wild yeast isolates harbor prion proteins, yet their impact on host-microbe interactions remains poorly characterized. Given the ecological dominance of yeasts in the Drosophila mycobiome, we leveraged the Drosophila melanogaster-Saccharomyces cerevisiae system to investigate how the mycobiome-derived prion, [MRPL10+], modulates host physiology. We show that flies exposed to [MRPL10+] yeast exhibit significantly enhanced cold tolerance and increased locomotor activity. This effect persists with heat-killed yeast and diluted culture, suggesting a stable, potent bioactive factor. Using the genetically diverse Drosophila Global Diversity Lines (GDL), we identified natural variation in responsiveness to [MRPL10+] yeast. Genome-wide association and functional RNAi screening revealed a gut-brain signaling axis involving genes critical for digestion, intercellular communication, transcription regulation, and neural transmission. Notably, serotonin and octopamine pathways were essential for [MRPL10+]-induced changes in cold tolerance and locomotion, implicating neuromodulatory circuits in prion-mediated microbial signaling. Our findings establish a mechanistic link between a fungal prion and host metabolic and neural adaptation. This work provides the first genetic dissection of a prion-mediated host-microbe interaction, laying the groundwork for investigating beneficial prions in complex microbial communities and highlighting a new dimension of the mycobiomes influence on animal physiology.

evolutionary biology↗

bioRxiv2026

Hunger neurons track available food locations during foraging and spatial memory recall

Foraging requires animals to integrate metabolic needs with knowledge of where resources are located. Agouti-related peptide (AgRP) neurons in the hypothalamus are central regulators of appetitive behaviors, yet their role in foraging remains poorly understood. Here, we used fiber photometry to record AgRP neuron activity in freely foraging mice and found that it dynamically tracks spatial proximity to food. AgRP neuron activity decreases progressively as mice approach the food source and increases as they move away, forming a gradient that scales with distance. Notably, this proximity signal emerges only in fasted mice once food is discovered, is specific to the accessible rather than to inaccessible sources, and persists where a source was previously available. Together, our findings reveal that AgRP neuron activity reflects distance to food in a dynamic, experience-dependent manner, extending what these neurons convey beyond internal need and food-related cues to include learned spatial information. HighlightsO_LIAgRP neuron activity reflects spatial distance to food sources during foraging C_LIO_LIAgRP neuron activity gradually decreases on approach to food and increases during departure C_LIO_LIAgRP distance signal depends on metabolic state, and its recall requires visual cues C_LIO_LIAgRP neuron activity tracks food source availability and its location after source removal C_LI

neuroscience↗

bioRxiv2026

Molecular architecture of excitatory and inhibitory neurons in the first gustatory relay

Taste perception is a major determinant of food intake and is dynamically modulated by hunger and satiety signals across species. While the peripheral and cortical representations of taste sensory stimuli are well characterized, far less is known about how metabolic state shapes taste processing in subcortical structures such as the brainstem. The rostral nucleus of the solitary tract (rNTS) is the first central relay for gustatory input, yet how fasting remodels transcriptional programs in rNTS neurons remains poorly defined. To address this gap, we performed cell-type-specific bulk nuclear RNA sequencing of molecularly defined excitatory (Vglut2+) and inhibitory (Vgat+) rNTS neurons. We combined Cre-dependent Sun1-sfGFP nuclear tagging with fluorescence-activated nuclear sorting to profile each population in ad libitum-fed and 24-hour-fasted mice. The two populations were transcriptionally distinct and differed in their baseline complement of hunger- and metabolic-sensing genes. Fasting elicited a transcriptional response that was largely restricted to excitatory, Vglut2+, rNTS neurons, while the inhibitory population was minimally affected. In excitatory neurons, fasting reduced the expression of Gabrd, the {delta} subunit of the GABAA receptor that mediates extrasynaptic tonic inhibition, while leaving synaptic GABAA subunits and the glutamatergic or GABAergic neurotransmission machinery unchanged. RNAscope in situ hybridization confirmed Gabrd expression in Vglut2+ rNTS neurons and showed that Gabrd is also expressed in the non-Vglut2+ population; the cell-type specificity of the fasting response therefore reflects differential regulation of a shared gene rather than its restricted expression. Our results identify a cell-type-specific, state-dependent transcriptional signature in which fasting downregulates a mediator of tonic GABAergic inhibition in excitatory rNTS neurons, providing a candidate substrate for the metabolic modulation of taste processing within the brainstem. HighlightsO_LIExcitatory and inhibitory rNTS neurons are intermingled, not spatially segregated, in rNTS C_LIO_LIVglut2+ and Vgat+ rNTS nuclear transcriptomes are distinct at baseline C_LIO_LIFasting reshapes the Vglut2+ transcriptome but leaves Vgat+ neurons largely unchanged C_LIO_LIFasting downregulates Gabrd, a mediator of tonic inhibition, in Vglut2+ neurons C_LI

neuroscience↗

bioRxiv2025

Social experience alters behaviors by reprogramming the Fruitless pathway and circadian state in Drosophila

From flies to humans, social experience affects various cognitive and behavioral processes. Previous studies have shown that group housing suppresses many behaviors like courtship, aggression, and feeding in Drosophila melanogaster, in addition to resetting the circadian state. Here, we focus on group housing-induced courtship suppression. To determine the mechanisms by which social experience modulates courtship behaviors, we performed bulk tissue RNAseq and single-cell RNAseq from cells expressing FruitlessM (FruM) and DoublesexM (DsxM), two transcription factors that label interconnected neural circuits for socially driven behaviors, from grouped or isolated male brains. These revealed that social isolation alters fru and dsx levels throughout the brain. Knocking down fruM in different fruM-positive neuron subpopulations in the brains has diverse effects on social experience-dependent changes in courtship. Furthermore, group housing increases the expression of stripe (sr) and Hormone receptor-like in 38 (Hr38) genes encoding neural activity-induced transcription factors in most neurons within social circuits. We found that knocking down sr in fruM-positive neurons effectively eliminates the impact of social experience by increasing courtship in group-housed males. Importantly, social experience also alters the expression of FruM/DsxM putative target genes regulating circadian states throughout the brain. Disrupting the function of multiple circadian genes diminishes the effect of group housing on courtship. Our findings suggest that group housing/social enrichment suppresses courtship by reprogramming the circadian arousal state, whereas courtship-elevating effects of social experience rely on unique influences of FruM expression and function in different neurons within social and clock circuits. These results are significant as they point to modulation of circadian arousal state as a possible central strategy for mediating the pleiotropic effects of social experience on organismal responses.

neuroscience↗

bioRxiv2024

A gut-brain-gut interoceptive circuit loop gates sugar ingestion in Drosophila

The communication between the brain and digestive tract is critical for optimising nutrient preference and food intake, yet the underlying neural mechanisms remain poorly understood1-7. Here, we show that a gut-brain-gut circuit loop gates sugar ingestion in flies. We discovered that brain neurons regulating food ingestion, IN18, receive excitatory input from enteric sensory neurons, which innervate the oesophagus and express the sugar receptor Gr43a. These enteric sensory neurons monitor the sugar content of food within the oesophagus during ingestion and send positive feedback signals to IN1s, stimulating the consumption of high-sugar foods. Connectome analyses reveal that IN1s form a core ingestion circuit. This interoceptive circuit receives synaptic input from enteric afferents and provides synaptic output to enteric motor neurons, which modulate the activity of muscles at the entry segments of the crop, a stomach-like food storage organ. While IN1s are persistently activated upon ingestion of sugar-rich foods, enteric motor neurons are continuously inhibited, causing the crop muscles to relax and enabling flies to consume large volumes of sugar. Our findings reveal a key interoceptive mechanism that underlies the rapid sensory monitoring and motor control of sugar ingestion within the digestive tract, optimising the diet of flies across varying metabolic states.

neuroscience↗

bioRxiv2024

Exploration-exploitation trade-off is regulated by metabolic state and taste value in Drosophila

Similar to other animals, the fly, Drosophila melanogaster, changes its foraging strategy from exploration to exploitation upon encountering a nutrient-rich food source. However, the impact of metabolic state or taste/nutrient value on exploration vs. exploitation decisions in flies is poorly understood. Here, we developed a one-source foraging assay that uses automated video tracking coupled with high-resolution measurements of food ingestion to investigate the behavioral variables flies use when foraging for food with different taste/caloric values and when in different metabolic states. We found that flies alter their foraging and ingestive behaviors based on their hunger state and the concentration of the sucrose solution. Interestingly, sugar-blind flies did not transition from exploration to exploitation upon finding a high-concentration sucrose solution, suggesting that taste sensory input, as opposed to post-ingestive nutrient feedback, plays a crucial role in determining the foraging decisions of flies. Using a Generalized Linear Model (GLM), we showed that hunger state and sugar volume ingested, but not the nutrient or taste value of the food, influence flies radial distance to the food source, a strong indicator of exploitation. Our behavioral paradigm and theoretical framework offer a promising avenue for investigating the neural mechanisms underlying state and value-based foraging decisions in flies, setting the stage for systematically identifying the neuronal circuits that drive these behaviors.

animal behavior and cognition↗

bioRxiv2024

HisCl1 regulates gustatory habituation in sweet taste neurons and mediates sugar ingestion in Drosophila

Similar to other animals, the fly, Drosophila melanogaster, reduces its responsiveness to tastants with repeated exposure, a phenomenon called gustatory habituation. Previous studies have focused on the circuit basis of gustatory habituation in the fly chemosensory system 1,2. However, gustatory neurons reduce their firing rate during repeated stimulation 3, suggesting that cell-autonomous mechanisms also contribute to habituation. Here, we used deep learning-based pose estimation and optogenetic stimulation to demonstrate that continuous activation of sweet taste neurons causes gustatory habituation in flies. We conducted a transgenic RNAi screen to identify genes involved in this process and found that knocking down Histamine-gated chloride channel subunit 1 (HisCl1) in the sweet taste neurons significantly reduced gustatory habituation. Anatomical analysis showed that HisCl1 is expressed in the sweet taste neurons of various chemosensory organs. Using single sensilla electrophysiology, we showed that sweet taste neurons reduced their firing rate with prolonged exposure to sucrose. Knocking down HisCl1 in sweet taste neurons suppressed gustatory habituation by reducing the spike frequency adaptation observed in these neurons during high-concentration sucrose stimulation. Finally, we showed that flies lacking HisCl1 in sweet taste neurons increased their consumption of high-concentration sucrose solution at their first meal bout compared to control flies. Together, our results demonstrate that HisCl1 tunes spike frequency adaptation in sweet taste neurons and contributes to gustatory habituation and food intake regulation in flies. Since HisCl1 is highly conserved across many dipteran and hymenopteran species, our findings open a new direction in studying insect gustatory habituation.

neuroscience↗

bioRxiv2023

GABA-mediated inhibition in visual feedback neurons fine-tunes Drosophila male courtship

Vision is critical for the regulation of mating behaviors in many species. Here, we discovered that the Drosophila ortholog of human GABAA-receptor-associated protein (GABARAP) is required to fine-tune male courtship by modulating the activity of visual feedback neurons, lamina tangential cells (Lat). GABARAP is a ubiquitin-like protein that regulates cell-surface levels of GABAA receptors. Knocking down GABARAP or GABAA receptors in Lat neurons or hyperactivating them induces male courtship toward other males. Inhibiting Lat neurons, on the other hand, delays copulation by impairing the ability of males to follow females. Remarkably, the human ortholog of Drosophila GABARAP restores function in Lat neurons. Using in vivo two-photon imaging and optogenetics, we show that Lat neurons are functionally connected to neural circuits that mediate visually-guided courtship pursuits in males. Our work reveals a novel physiological role for GABARAP in fine-tuning the activity of a visual circuit that tracks a mating partner during courtship.

neuroscience↗

bioRxiv2022

Neuromuscular embodiment of feedback control elements in Drosophila flight

While insects like Drosophila are flying, aerodynamic instabilities require that they make millisecond-timescale adjustments to their wing motion to stay aloft and on course. These stabilization reflexes can be modeled as a proportional-integral (PI) controller; however, it is unclear how such control might be instantiated in insects at the level of muscles and neurons. Here, we show that the b1 and b2 motor units--prominent components of the flys steering muscles system--modulate specific elements of the PI controller: the angular displacement (integral, I) and angular velocity (proportional, P), respectively. Moreover, these effects are observed only during the stabilization of pitch. Our results provide evidence for an organizational principle in which each muscle contributes to a specific functional role in flight control, a finding that highlights the power of using top-down behavioral modeling to guide bottom-up cellular manipulation studies.

animal behavior and cognition↗

bioRxiv2019

Non-invasive multiphoton imaging of neural structure and activity in Drosophila

We developed a multiphoton imaging method to capture neural structure and activity in behaving flies through the intact cuticles. Our measurements show that the fly head cuticle has surprisingly high transmission at wavelengths > 900 nm, and the difficulty of through-cuticle imaging is due to the air sacs and/or fat tissue underneath the head cuticle. By compressing the air sacs, we performed deep multiphoton imaging of fly brains through the intact cuticle. Our anatomical and functional imaging results show that 2- and 3-photon imaging are comparable in superficial regions such as the mushroom body, but 3-photon imaging is superior in deeper regions such as the central complex and beyond. We further demonstrated 2-photon through-cuticle functional imaging of odor-evoked calcium responses from the mushroom body {gamma}-lobes in behaving flies short-term and long-term (12 consecutive hours). The through-cuticle imaging method developed here extends the time limits of in vivo imaging in flies, and opens up new ways to capture neural structure and activity from the intact fly brain.

neuroscience↗

bioRxiv2018

An expression atlas of chemosensory ionotropic glutamate receptors identifies a molecular basis of carbonation detection

Taste perception is thought to involve the encoding of appetitive and aversive chemical cues in food through a limited number of sensory pathways. Through expression analysis of the complete repertoire of Drosophila Ionotropic Receptors (IRs), a sensory subfamily of ionotropic glutamate receptors, we reveal that the majority of IRs is expressed in diverse peripheral neuron populations across gustatory organs in both larvae and adults, implying numerous roles in taste-evoked behaviours. We characterise Ir56d, which labels two anatomically-distinct classes of neurons in the proboscis: one represents a subset of sugar- and fatty acid-sensing neurons, while the other responds to carbonated solutions and fatty acids. Mutational analysis shows that IR56d, together with the broadly-expressed co-receptors IR25a and IR76b, is essential for physiological activation by carbonation and fatty acids, but not sucrose. We further demonstrate that carbonation is behaviourally attractive to flies (in an IR56d-dependent manner), but in a distinct way to other appetitive stimuli. Our work provides a valuable toolkit for investigating the taste functions of IRs, defines a molecular basis of carbonation sensing, and illustrates how the gustatory system uses combinatorial expression of sensory receptors in distinct neuron types to coordinate behaviour.

neuroscience↗