Biology subjects

Kondo, S.

Publications and source records attributed to Kondo, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Epstein-Barr Virus in HIV-Associated Conjunctival Squamous Cell Carcinoma and Transcriptional Reprogramming of Conjunctival Epithelial Cells

The involvement of Epstein-Barr virus (EBV) in conjunctival squamous cell carcinoma (cSCC) remains incompletely defined. This study integrated analyses of primary tumors with an experimental model of the conjunctival epithelium. Five Nigerian tumors from patients with HIV and three Japanese tumors from patients without HIV were examined by EBV-encoded RNA in situ hybridization (EBER-ISH), EBV DNA PCR, and virome analysis of RNA sequencing data. EBER localized to epithelial tumor cells in four Nigerian specimens and none of the Japanese specimens. EBV DNA and RNA were each detected in three Nigerian tumors, with every EBER-positive tumor supported by at least one additional assay. Human telomerase reverse transcriptase-immortalized conjunctival epithelial cells infected with Akata-GFP-EBV expressed latency-associated and lytic viral genes. Comparison of three infected and three control cultures identified 96 differentially expressed host genes and 23 enriched Hallmark gene sets at a false discovery rate below 0.05. RT-qPCR confirmed increased HES1, CXCL8, CXCL2, and LOX and decreased FGFBP1, CSTA, SAPCD2, and TMEM40 expression. Prominent responses involved inflammatory signaling, epithelial remodeling, metabolism, and cell-cycle regulation. These findings identify tumor-cell-associated EBV in a subset of HIV-associated cSCC and establish an epithelial model for investigating infection-associated host responses.

microbiology↗

bioRxiv2026

Dual role of the RIG-I 2CARD as a signaling module and a brake on dsRNA translocation

RIG-I is an innate immune receptor for viral double-stranded RNA (dsRNA). Upon binding dsRNA, RIG-I nucleates MAVS filaments through its two caspase activation and recruitment domains (2CARD). However, how the 2CARD behaves during activation has remained unclear. Using high-speed atomic force microscopy, we visualized the 2CARD in full-length RIG-I across its apo, dsRNA-bound, translocating, multimeric, and polyubiquitin-bound states. Protrusions consistent with the 2CARD appeared only transiently in the apo state, whereas a mobile 2CARD emerged upon RNA binding. During ATP-driven translocation, wild-type RIG-I moved approximately twofold slower and showed more frequent pauses and multimers than RIG-I {Delta}2CARD. Within multimers, 2CARDs formed a complex that polyubiquitin stabilized into larger, dsRNA-deforming assemblies. These findings reveal the 2CARD as a brake on the RIG-I motor, beyond signaling.

biophysics↗

bioRxiv2026

ABC transporters support Drosophila intestinal stem and progenitor cells during cytotoxic challenge

Adult stem cells can survive diverse insults, from ionizing radiation to toxic chemicals. In vertebrates, ABC transporter expression and dye-efflux capacity have been associated with stem-cell protection and multidrug resistance. How compound accumulation differs between adult stem cells and their differentiated daughters within an intact tissue remains poorly understood. Here, we show that adult Drosophila intestinal stem/progenitor cells maintain a distinct low-accumulation state for membrane-permeable compounds and that ABC transporters contribute to this phenotype and to the response to cytotoxic stress. Across nine membrane-permeable probes, stem/progenitor cells accumulated eight at lower levels than differentiated enterocytes. We selected tetramethylrhodamine methyl ester (TMRM), a membrane-permeable fluorescent probe that showed a strong difference in accumulation between stem/progenitor cells and enterocytes, as a quantitative readout for an RNAi screen of all 56 Drosophila ABC-family genes. The screen identified seven candidate transporters whose depletion increased the stem/progenitor-to-enterocyte TMRM fluorescence ratio. Further characterization of one of them, ABCB7, showed that ABCB7-depleted guts contained fewer mitotic cells during cytotoxic drug exposure. These results implicate ABC transporters in lower compound accumulation in Drosophila intestinal stem/progenitor cells and support a role for ABC transporters in their response to cytotoxic challenge.

genetics↗

bioRxiv2026

Neuropeptide T2A-GAL4 knock-ins illustrate practical considerations for interpreting GAL4 reporter patterns in Drosophila

Transgenic GAL4 lines are widely used in Drosophila to label and manipulate specific cell types, but the resulting reporter expression patterns do not always represent ongoing driver activity. We generated a collection of neuropeptide T2A-GAL4 knock-ins and characterized their expression by native-fluorescence imaging using UAS-CD8::GFP and a Brp-miRFP680 knock-in, eliminating the need for immunostaining. During characterization of these lines, we observed cases in which adult GFP patterns did not match the on-going GAL4 activity, as well as cases in which GAL4 produced adverse cellular effects. Using temperature-sensitive GAL80, we found that adult GFP expression in certain neurons driven by CCHa2-T2A-GAL4 and Dsk-T2A-GAL4 depended on GAL4 activity before eclosion and was not reproduced by adult-only induction. Several GAL4 lines also showed dominant developmental phenotypes. Heterozygous Burs-T2A-GAL4 animals, for example, displayed wing-expansion defects that were fully suppressed by GAL80. Severe wing defects were not accompanied by a reduction in the number of reporter-labeled neurons before eclosion, but the morphology of these neurons were affected. These observations illustrate how developmental driver history and GAL4-associated cellular effects can influence reporter patterns in the adult nervous system.

genetics↗

bioRxiv2026

Generation of lachrymatory factor synthase-suppressed onion (Allium cepa L.) by Agrobacterium-mediated gene transfer for CRISPR/Cas9 genome editing

Lachrymatory factor, an irritating volatile with tear-inducing property, is produced when onion bulbs are cut or chopped. We aimed to generate onion plants with reduced lachrymatory factor synthase (LFS) activity via clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (CRISPR/Cas9) genome editing. Calli induced from primary roots were transformed with Agrobacterium tumefaciens carrying expression cassettes for CRISPR/Cas9, guide RNA, green fluorescent protein (GFP), and hygromycin resistance; callus lines that showed a high-frequency stable GFP expression were selected as "elite callus lines" that were suitable for transformation. Cleaved amplified polymorphic sequence (CAPS), heteroduplex mobility assay (HMA), and Sanger sequencing confirmed mutations introduced into the LFS gene, and plants were regenerated from the confirmed LFS-edited callus lines. The LFS enzyme activity in the leaves and bulbs of the LFS-edited plants was lower than that in control plants, while the LFS-edited plants exhibited severe growth abnormalities and failed to set seed, possibly due to long-term culture to maintain the elite callus line. The present study first demonstrated that onion genome editing, which modified a specific trait of onion, the reduction of LFS activity, was achieved. The results obtained opened the feasible way toward the final goal: the production of tear-free, higher health-functional onions.

plant biology↗

bioRxiv2026

RPL38 controls 60S ribosomal subunit homeostasis to regulate start-codon stringency and frame selection during C9ORF72 RAN translation

Translation initiation depends on stringent start-codon recognition, yet how ribosomal states modulate initiation stringency remains incompletely defined. Repeat-associated non-AUG (RAN) translation is a non-canonical initiation pathway that generates toxic dipeptide repeat proteins in C9ORF72-associated frontotemporal dementia and amyotrophic lateral sclerosis (FTD/ALS). Here, we performed a dual-luciferase reporter-based siRNA screen to identify factors that differentially regulate canonical AUG-initiated and C9ORF72 RAN translation. We identified the 60S ribosomal protein RPL38 as a key determinant of translational output. RPL38 depletion selectively suppressed AUG-dependent translation while relatively preserving near-cognate-initiated RAN translation, resulting in a dose-dependent increase in the RAN-to-AUG translation ratio. Polysome profiling showed a selective reduction in large ribosomal subunit abundance without impaired subunit joining, consistent with defective 60S subunit homeostasis. Substitution of a near-cognate CUG start codon with AUG rendered translation sensitive to RPL38 depletion, supporting a role for ribosomal subunit availability in modulating initiation stringency. Graded RPL38 depletion altered frame usage within C9ORF72 repeat RNA. Consistent with these findings, RPL38 knockdown in the Drosophila eye enhanced GR-frame RAN translation while suppressing canonical AUG-dependent translation. Collectively, these findings identify 60S ribosomal subunit availability as a key determinant of start-codon stringency and frame selection in pathological C9ORF72 RAN translation.

molecular biology↗

bioRxiv2026

The mechanosensitive protein Zyxin influences Hippo signalling and tissue growth via adherens junctions and basal spot junctions in Drosophila

Physical forces like tension and compression have a central role in the growth and morphogenesis of tissues. Cell-cell junctions and the actin cytoskeleton are key mediators of physical forces and influence activity of signalling networks like the Hippo pathway. Here, we show that the mechanosensitive proteins Zyxin and Ajuba work in concert to limit Hippo signalling and promote Drosophila epithelial tissue growth. Zyxin recruits both Ajuba and the central Hippo pathway kinase Warts to adherens junctions and basal spot junctions, and limit Warts activity by segregating it from Hippo pathway activator proteins. Zyxin also promotes the transmission of actomyosin tension to adherens junctions in growing epithelial tissues, indicating conservation of this function. Thus, we provide new insights into how Zyxin couples mechanical cues and Hippo pathway-dependent tissue growth and highlight the importance of basal spot junctions and their associated actomyosin network in epithelial tissue development.

developmental biology↗

bioRxiv2026

A collagen orientation switch reshapes fin architecture

The orientation and distribution of fibrillar collagen are critical determinants of the shape and mechanical properties of bones and organs.1-3 However, how they are spatially organized within tissues is still poorly understood,4-7 as visualizing these collagen architectures remains challenging. Actinotrichia (AT), the spear-shaped fibrillar collagen structures located at the distal tips of fish fins, are easily observable due to their large size and distinctive morphology8-14 and have recently emerged as a model system for studying collagen fiber organization.15-19 In this study, we generated knockout lines for the fish-specific extracellular matrix (ECM) genes actinodin1 and actinodin2 (and1/2), which are lost in tetrapods.12 Loss of these genes dramatically altered the orientation of collagen fibers, thereby inducing changes in fin morphology. In the wild-type fins, AT are orderly arranged beneath the epidermis, forming layers parallel to the fin surface, and their individual fibers radiate distally toward the fin tip. In contrast, double knockout (dKO) of and1/2 results in overall fin reduction accompanied by increased thickness. Examination of the collagen structure distribution revealed the presence of aberrant collagen fibers oriented perpendicular to the fin epidermis. Moreover, the vertically oriented fibers contributed to thickening of the mesenchymal region in which they were distributed. The number of abnormal fibers increased with the severity of and1/2 deficiency, suggesting that collagen fibers in fins inherently tend to align perpendicular to the epidermis when these genes are absent. Furthermore, in tetrapods lacking the and gene family--specifically amphibians, the tetrapod group most closely related to fish20--examination of the developing limb, the organ homologous to paired fins in fish,21 revealed collagen fibers oriented perpendicular to the epidermis. The distribution pattern also resembled that observed in the fin buds of and1/2 dKO fish. Together, these findings highlight collagen patterning alterations as a previously unrecognized factor contributing to the evolutionary divergence between thinned fins and thickened limbs. Moreover, the identification of mutants that dramatically alter collagen fiber orientation is unprecedented, suggesting that analysis of Actinodin (And) function unveil the mechanisms underlying collagen matrix formation.22-28

developmental biology↗

bioRxiv2025

Morphogenesis of the Carapace from Phyllosoma to Puerulus in Spiny Lobsters

Molting in exoskeleton-bearing organisms can result in dramatic body shape transformations. While this phenomenon has been well-studied in insects, limited knowledge exists for other taxa, including crustaceans. Among crustaceans, achelatan lobsters, such as Palinuridae and Scyllaridae, exhibit a unique metamorphic transition from a flattened phyllosoma larva to a three-dimensional puerulus or nisto larva in a single molt. This study investigates the mechanisms underlying this transformation, focusing on carapace deformation through histological analysis, live imaging, and computational modeling. Three-dimensional micro-computed tomography revealed a significant reduction in body length during metamorphosis. Live imaging captured dynamic morphological changes, including epithelial contraction and subsequent reshaping. Scanning electron microscopy identified a distinctive furrow structure on the carapace surface, absent in post-molt puerulus larvae, suggesting a role in the transformation process. To explore the formation of this furrow pattern, a computational model was developed based on differential shrinkage rates in vertical and horizontal directions. The model successfully reproduced similar patterns observed in natural specimens, implying that controlled anisotropic contraction could contribute to morphogenesis. Furthermore, three-dimensional shrinkage simulations demonstrated that local contraction with constrained out-of-plane deformation can generate folds, which later expand to form curved structures. This study provides novel insights into the biomechanics of arthropod molting, highlighting a previously unrecognized mechanism of two-dimensional-to-three-dimensional transformation. The findings enhance our understanding of achelatan lobster development and offer broader implications for exoskeletal morphogenesis across arthropods.

developmental biology↗

bioRxiv2025

Cellular fitness is determined by ribosomal protein S12-mediated release of a truncated Xrp1

Multicellular tissues require continuous optimization to maintain their structure and function by actively eliminating viable, yet unfit cells via a mechanism known as cell competition. During this process, unfit loser cells commonly upregulate the C/EBP family transcription factor Xrp1, which causes their elimination, indicating that intracellular Xrp1 levels determine cellular fitness. However, despite its central role, the mechanism by which Xrp1 is upregulated in unfit cells remains unknown. Here, we show that Xrp1 is upregulated through a previously unrecognized post-transcriptional regulatory mechanism mediated by the ribosomal protein S12 (RpS12). Surprisingly, Xrp1 mRNA is abundantly expressed even in wild-type cells, yet it is not translated. This is due to an upstream open reading frame (uORF) located in the 5UTR of the initial coding exon of Xrp1 mRNA, which inhibits the translation of the main Xrp1 ORF. Intriguingly, in unfit cells, RpS12 causes splicing-mediated skipping of this initial exon, leading to the use of an alternate start codon that generates a short isoform of Xrp1 protein, causing cell death. Notably, protein structural analysis reveals that RpS12 is highly homologous to that of a spliceosomal component SNU13, suggesting the role of RpS12 in directly regulating alternative splicing of Xrp1 mRNA. Our findings thus provide not only a mechanistic insights into how cellular fitness is determined but also how tissue optimization is achieved.

cell biology↗

bioRxiv2025

Ion transport peptide regulates body water balance via a receptor guanylyl cyclase in the Drosophila hindgut

Maintaining internal water balance, including ionic and osmotic balance, is critical for animal development and survival. In insects, internal water balance is regulated through the Malpighian tubules and the hindgut, which transport water and ions across their epithelia under the regulation of multiple peptide hormones. One of these, ion transport peptide (ITP), a member of the highly conserved crustacean hyperglycemic hormone superfamily among ecdysozoans, is an anti-diuretic hormone in insects, but its mechanism of action remains largely unclear. Here, we show that the short amidated isoform of ITP (saITP), secreted from brain neurosecretory cells, regulates water absorption via the receptor guanylyl cyclase (rGC) Gyc76C in the hindgut of the fruit fly Drosophila melanogaster. Both ITP and Gyc76C are evolutionarily conserved and are essential for larval survival in D. melanogaster, as mutation or knockdown of either gene results in early larval lethality. In Drosophila S2 cells, synthetic saITP increases intracellular cyclic GMP (cGMP) in a Gyc76C-dependent manner, an effect abolished by deletion of its putative ligand-binding domain. Using the fluorescent cGMP biosensor RedcGull in ex vivo-cultured hindguts, we found that saITP increases epithelial cGMP levels, and this response requires Gyc76C. Consistently, saITP promotes hindgut water reabsorption via Gyc76C. Thus, saITP acts via Gyc76C in a brain-hindgut neuroendocrine axis that regulates internal water balance during development. Our study provides new insight into the neuroendocrine control of osmoregulation in ecdysozoans and supports a broader role for rGCs in peptide-hormone signaling.

physiology↗

bioRxiv2025

Reproducibility of Scientific Claims in Drosophila Immunity: A Retrospective Analysis of 400 Publications

Drosophila immunity has been the focus of intense study and has impacted other research fields including innate immunity and agriculturally or epidemiologically relevant investigations of insect pests and vectors. Unsurprisingly for such a large body of work, some published results were later found to be irreplicable. Although some results have been contradicted in the literature, many have no published follow-up, either due to a lack of research or low motivation to publish negative or contradictory results. We have addressed this by performing a reproducibility project that analyses the conceptual replicability of claims from articles published on Drosophila immunity before 2011. To assess replicability, we extracted claims from 400 articles on the Drosophila immune response to bacteria and fungi and performed preliminary verification by comparing these claims to other published literature in the field. Using alternative approaches, we also experimentally tested some unchallenged claims, with no published follow-up. The intent of this analysis was to centralize evidence on insights and findings to improve clarity for scientists that may base research programs on these data. Although the aim of the ReproSci project is to assess the replicability of claims made in articles published in the field of Drosophila immunity, it is in no way an assessment of the scientific value of the research. All our data are published on a publicly available website associated with this article (https://ReproSci.epfl.ch/) that encourages community participation. This article provides a short summary of claims that were found to have contradictory evidence, which may help the community to assess past findings on Drosophila immunity and improve clarity going forward. Statistical analysis of this reproducibility study and metascience insights obtained from this approach are discussed in a companion article.

genetics↗

bioRxiv2024

Stress-induced organismal death is genetically regulated by the mTOR-Zeste-Phae1 axis

All organisms are exposed to various stressors, which can sometimes lead to organismal death, depending on their intensity. While stress-induced organismal death has been observed in many species, the underlying mechanisms remain unclear. In this study, we investigated the molecular mechanisms of stress-induced organismal death in the fruit fly Drosophila melanogaster. We identified a chymotrypsin-like serine protease Phaedra1 (Phae1) as a death mediator in D. melanogaster larvae. Phae1 expression was upregulated by lethal heat stress (40 {degrees}C) but not non-lethal heat stress (38 {degrees}C or lower). The most prominent induction of Phae1 occurred in the central nervous system (CNS). We found neuro-specific knockdown of Phae1 increased survival and reduced neuronal caspase activity following exposure to lethal heat stress, suggesting that the transcriptional upregulation of Phae1 in the CNS is essential for stress-induced organismal death. We next found via bioinformatic and biochemical analyses that the transcription factor Zeste (Z) bound the Phae1 enhancer region and that z loss-of-function impaired Phae1 induction in the CNS, increasing survival following lethal heat stress. In addition, we found via chemical screening that rapamycin, a chemical inhibitor of mechanistic target of rapamycin (mTOR), suppressed Phae1 expression. Neuro-specific knockdown of mTor reduced the protein levels of both Phae1 and Z, leading to an increase in survival following lethal heat stress. Together, these results indicate that heat stress-induced organismal death in D. melanogaster larvae is regulated by a genetically encoded transcriptional signaling pathway involving the mTOR-Z-Phae1 axis.

physiology↗

bioRxiv2024

Synapse profiling of identified neurons in the Drosophila brain

Characterization of intracellular synapse heterogeneity aides to understand the intricate computational logic of neuronal circuits. Despite recent advances in connectomics, the spatial patterns of synapses and their inter-individual variability remain largely unknown. Using directed split-GFP reconstitution, we achieved visualization of endogenous Bruchpilot (Brp), a presynaptic active zone (AZ) scaffold protein, in a cell-type-specific manner. By developing a high-throughput quantification pipeline, we profiled AZ structures in identified neurons of the mushroom body circuit, where intracellular synaptic patterns are crucial due to compartmentalized connectivity. Quantitative characterization of the pattern of Brp clusters across multiple individuals revealed cell-type-dependent synapse heterogeneity and stereotypy. Furthermore, we discovered previously unidentified sub-compartmental synapse configuration and its transient structural plasticity triggered by associative learning. These profiles thus uncovered multi-layered spatial configurations of AZs, from stereotyped overall AZ distribution patterns, to local arrangements of neighboring synapses.

neuroscience↗

bioRxiv2024

Octopamine signals coordinate the spatial pattern of presynaptic machineries in the Drosophila mushroom bodies

Neurons need to adjust synaptic output according to the targets. However, the target-specific synaptic structures within individual neurons in the central nervous system remains unresolved. Applying the CRISPR/Cas9-mediated split-GFP tagging, we visualized the endogenous active zone scaffold protein, Bruchpilot (Brp), in specific cells. This technology enabled the spatial characterization of presynaptic machineries only within the Kenyon cells (KCs) of the Drosophila mushroom bodies. We found the patterned accumulation of Brp among the compartments of axon terminals, where a KC synapses onto different postsynaptic neurons. Mechanistically, the localized octopaminergic modulation along {gamma} KC terminals regulate this compartmental Brp heterogeneity via Oct{beta}2R and cAMP signaling. We further found that acute food deprivation reorganizes this spatial pattern in an octopamine-dependent manner. Such coordinated regulation of local synaptic machineries thus explains how the mushroom bodies integrate changing physiological states. This subcellular information processing represents an elegant solution to expand computational capacity of the circuit.

neuroscience↗

bioRxiv2024

Synaptic input architecture of visual cortical neurons revealed by large-scale synapse imaging without backpropagating action potentials

How neurons integrate thousands of synaptic inputs to compute sharply tuned outputs is a critical question in sensory information processing. To answer this question, it is essential to record the location and activity of synaptic inputs in vivo. However, back-propagating action potential (BAP) calcium signals invade dendrites and spines, making accurate recording of spine responses difficult. In this study, we first developed a new method to record spine calcium responses without BAP signals. Using this method, we performed large-scale imaging of visually evoked spine activity from layer 2/3 pyramidal neurons and revealed three patterns of dendritic functional architectures of synaptic inputs: dendrites with clusters of spines of similar responses, dendrites with spines of diverse responses, and dendrites with spines where the majority of them show no visual response. Our model suggests that only a small fraction of spines on dendrites of clustered architectures are sufficient to generate sharply tuned output.

neuroscience↗

bioRxiv2024

Genetic analysis of the X-linked Adrenoleukodystrophy ABCD1 gene in Drosophila uncovers a role in Peroxisomal dynamics

X-linked adrenoleukodystrophy (X-ALD) is a progressive neurodegenerative disorder caused by a loss-of-function (LOF) mutation in the ATP-binding cassette subfamily D member 1 (ABCD1) gene, leading to the accumulation of very long-chain fatty acids (VLCFAs). This disorder exhibits striking heterogeneity; some male patients develop an early childhood neuroinflammatory demyelination disorder, while other patients, including adult males and most affected female carriers, experience a chronic progressive myelopathy. Adrenocortical failure is observed in almost all male patients, with age of onset varying sometimes being the first diagnostic finding. The gene underlying this spectrum of disease encodes an ATP-binding cassette (ABC) transporter that localizes to peroxisomes and facilitates VLCFA transport. X-ALD is considered a single peroxisomal component defect and does not play a direct role in peroxisome assembly. Drosophila models of other peroxisomal genes have provided mechanistic insight into some of the neurodegenerative mechanisms with reduced lifespan, retinal degeneration, and VLCFA accumulation. Here, we perform a genetic analysis of the fly ABCD1 ortholog Abcd1 (CG2316). Knockdown or deficiency of Abcd1 leads to VLCFA accumulation, salivary gland defects, locomotor impairment and retinal lipid abnormalities. Interestingly, there is also evidence of reduced peroxisomal numbers. Flies overexpressing the human cDNA for ABCD1 display a wing crumpling phenotype characteristic of the pex2 loss-of-function. Surprisingly, overexpression of human ABCD1 appears to inhibit or overwhelm peroxisomal biogenesis to levels similar to null mutations in fly pex2, pex16 and pex3. Drosophila Abcd1 is therefore implicated in peroxisomal number, and overexpression of the human ABCD1 gene acts a potent inhibitor of peroxisomal biogenesis in flies.

genetics↗

bioRxiv2024

Cell-type-specific fluorescent tagging of endogenous target proteins reveals synaptic enrichment and dynamic regulations of dopamine receptors

Dopamine can play opposing physiological roles depending on the receptor subtype. In the fruit fly Drosophila melanogaster, Dop1R1 and Dop2R encode the D1- and D2-like receptors, respectively, and are reported to oppositely regulate intracellular cAMP levels. Here, we profiled the expression and subcellular localization of endogenous Dop1R1 and Dop2R in specific cell types in the mushroom body circuit. For cell-type-specific visualization of endogenous proteins, we employed reconstitution of split-GFP tagged to the receptor proteins. We detected dopamine receptors at both presynaptic and postsynaptic sites in multiple cell types. Quantitative analysis revealed enrichment of both receptors at the presynaptic sites, with Dop2R showing a greater degree of localization than Dop1R1. The presynaptic localization of Dop1R1 and Dop2R in dopamine neurons suggests dual feedback regulation as autoreceptors. Furthermore, we discovered a starvation-dependent, bidirectional modulation of the presynaptic receptor expression in the PAM and PPL1 clusters, two distinct subsets of dopamine neurons, suggesting regulation of appetitive behaviors. Our results highlight the significance of the co-expression of the two opposing dopamine receptors in the spatial and conditional regulation of dopamine responses in neurons.

neuroscience↗