Biology subjects

Luo, J.

Publications and source records attributed to Luo, J..

At least 181 records · Page 10Linked to original sources

bioRxiv2023

The 14-3-3/spastin pathway coordinates neurite regeneration and recovery of spinal cord injury by targeting microtubule dynamics

Axon regeneration is abortive in the central nervous system following injury. Orchestrating microtubule dynamics has emerged as a promising approach to improve axonal regeneration. The microtubule severing enzyme spastin is essential for axonal development and regeneration through remodeling of microtubule arrangement. To date, however, little is known regarding the mechanisms underlying spastin action in neural regeneration after spinal cord injury. Here, we use glutathione transferase pulldown and immunoprecipitation assays to demonstrate that 14-3-3 interacts with spastin, both in vivo and in vitro, via spastin Ser233 phosphorylation. Moreover, we show that 14-3-3 protects spastin from degradation by inhibiting the ubiquitination pathway and upregulates the spastin-dependent severing ability. Furthermore, the 14-3-3 agonist Fusicoccin (FC-A) promotes neurite outgrowth and regeneration in vitro which needs spastin activation. Western blot and immunofluorescence results revealed that 14-3-3 protein is upregulated in the neuronal compartment after spinal cord injury in vivo. In addition, administration of FC-A not only promotes locomotor recovery, but also nerve regeneration following spinal cord injury in both contusion and lateral hemisection models; however, application of spastin inhibitor spastazoline successfully reverses these phenomena. Taken together, these results indicate that 14-3-3 is a molecular switch that regulates spastin protein levels, and the small molecule 14-3-3 agonist FC-A effectively mediates the recovery of spinal cord injury in mice which requires spastin participation. HighlightsO_LIThe formation of the 14-3-3 and spastin protein complex requires phosphorylation of spastin at the S233 site. C_LIO_LI14-3-3 is involved in the phosphorylation-ubiquitination crosstalk of spastin, thus impacting the protein stability. C_LIO_LI14-3-3 agonists Fusicoccin-A can facilitate the repair of spinal cord injury in mice. C_LIO_LIActivation of spastin function is a prerequisite for nerve regeneration and recovery of spinal cord injury in mice. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=129 SRC="FIGDIR/small/550600v3_ufig1.gif" ALT="Figure 1"> View larger version (66K): org.highwire.dtl.DTLVardef@ebabb6org.highwire.dtl.DTLVardef@5651caorg.highwire.dtl.DTLVardef@113df6borg.highwire.dtl.DTLVardef@1b0ea5a_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

A microfluidic strategy to capture antigen-specific high affinity B cells

Assessing B cell affinity to pathogen-specific antigens prior to or following exposure could facilitate the assessment of immune status. Current standard tools to assess antigen-specific B cell responses focus on equilibrium binding of the secreted antibody in serum. These methods are costly, time-consuming, and assess antibody affinity under zero-force. Recent findings indicate that force may influence BCR-antigen binding interactions and thus immune status. Here, we designed a simple laminar flow microfluidic chamber in which the antigen (hemagglutinin of influenza A) is bound to the chamber surface to assess antigen-specific BCR binding affinity of five hemagglutinin-specific hybridomas under 65- to 650-pN force range. Our results demonstrate that both increasing shear force and bound lifetime can be used to enrich antigen-specific high affinity B cells. The affinity of the membrane-bound BCR in the flow chamber correlates well with the affinity of the matched antibodies measured in solution. These findings demonstrate that a microfluidic strategy can rapidly assess BCR-antigen binding properties and identify antigen-specific high affinity B cells. This strategy has the potential to both assess functional immune status from peripheral B cells and be a cost-effective way of identifying individual B cells as antibody sources for a range of clinical applications.

bioengineering↗

bioRxiv2023

Pan-cancer analysis reveals embryonic and hematopoietic stem cell signatures to distinguish different cancer subtypes

PurposeStem cells-like properties in cancer cells may confer cancer development and therapy resistance. With the advancement of multi-omics technology, the multi-omics-based exploration of cancer stemness has attracted certain interests. However, subtyping of cancer based on the combination of different types of stem cell signatures remains scarce. MethodsIn this study, 10,323 cancer specimens from 33 TCGA cancer types were clustered based on the enrichment scores of six stemness gene sets, representing two types of stem cell backgrounds: embryonic stem cells (ESCs) and hematopoietic stem cells (HSCs). ResultsWe identified four subtypes of pan-cancer, termed StC1, StC2, StC3 and StC4, which displayed distinct molecular and clinical features, including stemness, genome integrity, intratumor heterogeneity, methylation levels, tumor microenvironment, tumor progression, chemotherapy and immunotherapy responses, and survival prognosis. This subtyping method for pan-cancer is reproducible at the protein level. ConclusionOur findings indicate that the ESC signature is an adverse prognostic factor, while the HSC signature and ratio of HSC/ESC signatures are positive prognostic factors in cancer. The ESC and HSC signatures-based subtyping of cancer may provide insights into cancer biology and clinical implications of cancer.

bioinformatics↗

bioRxiv2023

Visualizing alpha-synuclein and iron deposition in M83 mouse model of Parkinson's disease in vivo

BackgroundAbnormal alpha-synuclein and iron accumulation in the brain play an important role in Parkinsons disease (PD). Herein, we aim at visualizing alpha-synuclein inclusions and iron deposition in the brains of M83 (A53T) mouse models of PD in vivo. MethodsFluorescently labelled pyrimidoindole-derivative THK-565 was characterized by using recombinant fibrils and brains from 10-11 months old M83 mice, which subsequently underwent in vivo concurrent wide-field fluorescence and volumetric multispectral optoacoustic tomography (vMSOT) imaging. The in vivo results were verified against structural and susceptibility weighted imaging (SWI) magnetic resonance imaging (MRI) at 9.4 Tesla and scanning transmission X-ray microscopy (STXM) of perfused brains. Brain slice immunofluorescence and Prussian blue staining were further performed to validate the detection of alpha-synuclein inclusions and iron deposition in the brain, respectively. ResultsTHK-565 showed increased fluorescence upon binding to recombinant alpha-synuclein fibrils and alpha-synuclein inclusions in post-mortem brain slices from patients with Parkinsons disease and M83 mice. i.v. administration of THK-565 in M83 mice showed higher cerebral retention at 20 and 40 minutes post-injection by wide-field fluorescence compared to non-transgenic littermate mice, in congruence with the vMSOT findings. SWI/phase images and Prussian blue indicated the accumulation of iron deposits in the brains of M83 mice, presumably in the Fe3+ form, as evinced by the STXM results. ConclusionWe demonstrated in vivo mapping of alpha-synuclein by means of non-invasive epifluorescence and vMSOT imaging assisted with a targeted THK-565 label and SWI/STXM identification of iron deposits in M83 mouse brains ex vivo.

neuroscience↗

bioRxiv2023

Leucine alleviates cytokine storm syndrome by regulating macrophage polarization via the mTORC1/LXRα signaling pathway

Cytokine storms are associated with severe pathological damage and death in some diseases. Excessive activation of M1 macrophages and the subsequent secretion of pro-inflammatory cytokines are a major cause of cytokine storms. Therefore, promoting the polarization of M2 macrophages to restore immune balance is a promising therapeutic strategy for treating cytokine storm syndrome (CSS). This study was aimed at investigating the potential protective effects of leucine on lipopolysaccharide (LPS)-induced CSS in mice and exploring the underlying mechanisms. CSS was induced by LPS administration in mice, which were concurrently administered leucine orally. In vitro, BMDMs were polarized to M1 and M2 phenotypes with LPS and IL-4, respectively, and treated with leucine. Leucine decreased mortality in mice treated with lethal doses of LPS. Specifically, leucine decreased M1 polarization and promoted M2 polarization, thus diminishing pro-inflammatory cytokine levels and ameliorating CSS in mice. Further studies revealed that leucine induced macrophage polarization through the mechanistic target of rapamycin complex 1 (mTORC1)/liver X receptor (LXR) pathway, which synergistically enhanced the expression of the IL-4-induced M2 marker Arg1 and subsequent M2 polarization. In summary, this study revealed that leucine ameliorates CSS in LPS mice by promoting M2 polarization through the mTORC1/LXR/Arg1 signaling pathway. Our findings indicate that a fundamental link between metabolism and immunity contributes to the resolution of inflammation and the repair of damaged tissues.

immunology↗

bioRxiv2023

Genome-wide identification of silencers in human cells

Transcriptional regulation is a complex process that is controlled by a variety of factors, including enhancers and silencers. Silencers, also known as repressor elements, play a crucial role in the fine-tuning of gene expression by inhibiting or suppressing transcription in the human genome. Although significant progresses have been made, genome-wide silencer research is still in its early stages. Here, we used a genome-wide method called massively parallel reporter assays (MPRAs) to identify silencers in three human cell lines: K562, LNCap, and HEK293T. We identified 739,434, 643,484, and 491,952 silencer regions in these cell lines, respectively. We found that most of the silencers we identified had inhibitory activity and significantly enriched inhibitory motifs. These results confirm that silencers are ubiquitous in the human genome and play an important role in regulating gene expression. Therefore, our study provides a general strategy for genome-wide functional identification of silencer elements. This information could be used to better understand the mechanisms of gene regulation and to develop new therapeutic strategies for diseases that are caused by dysregulation of gene expression.

genomics↗

bioRxiv2023

Co-occurrence of ST412 Klebsiella pneumoniae isolates with hypermucoviscous and no-mucoviscous phenotypes in a short-term hospitalized patient

Hypermucoviscosity(HMV) is a phenotype that is commonly associated with hypervirulence in Klebsiella pneumoniae. The factors that contribute to the emergence of HMV subpopulations remain unclear. In this study, eight K. pneumoniae strains were recovered from an inpatient who were hospitalized for 20 days. Three of the isolates exhibited a non-HMV phenotype, which was concomitant with increased biofilm formation and higher siderophore secretion than the other five HMV isolates. All eight isolates were highly susceptible to serum killing, albeit HMV strains were remarkably more infective than non-HMV counterparts in a mouse model of infection. Whole genome sequencing(WGS) showed that the eight isolates belonged to the K57-ST412 lineage. Average nucleotide identity(ANI) analysis indicated that eight isolates share 99.96% to 99.99% similarity and were confirmed to be the same clone. Through comparative genomics analysis, 12 non-synonymous mutations were found among these isolates, seven of which in the non-HMV variants, including rmpA(R96G) and wbap (S435R), which are assumed to be associated with the non-HMV phenotype. The mutations manB(G440L), dmsB(R193W) and tkt(A643N) occurred in HMV isolates only. RNA-Seq and RT-qPCR revealed transcripts of genes involved in transporter activity, carbohydrate metabolism and energy metabolism, including cysK, paaF, vasD, celC and fruA, to be significantly dysregulated in the non-HMV strain K201060 compared to the HMV strain K201059, suggesting a participation in HMV phenotype development. This study suggests that co-occurrence of HMV and non-HMV phenotypes in the same clonal population may be mediated by mutational mechanisms as well as by certain genes involved in transport and central metabolism. ImportanceK. pneumoniae with a hypermucoviscosity(HMV) phenotype is a community-acquired pathogen that associated with increased invasiveness and pathogenicity, and underlying diseases are the most common comorbid risk factors inducing metastatic complications. HMV was earlier attributed to the overproduction of capsular polysaccharide, and more data point to the possibility of several causes contribute to this bacterial phenotype. Here, we describe a unique event in which the same clonal population showed both HMV and non-HMV characteristics. Studies have demonstrated that this process is influenced by mutational processes and genes related to transport and central metabolism. These finding provide fresh insight into the mechanisms between behind co-occurrence of HMV and non-HMV phenotypes in monoclonal populations as well as potentially being critical in developing strategies to control the further spread of HMV K. pneumoniae.

microbiology↗

bioRxiv2023

cProSite: A web based interactive platform for online proteomics, phosphoproteomics, and genomics data analysis

We developed cProSite, a website that provides online genomics, proteomics, and phosphoproteomics analysis for the data of The National Cancer Institutes Clinical Proteomic Tumor Analysis Consortium (CPTAC). This tool focuses on comparisons and correlations between different proteins and mRNAs of tumors and normal tissues. Our website is designed with biologists and clinicians in mind, with a user-friendly environment and fast search engine. The search results of cProSite can be used for clinical data validation and provide useful strategic information to identify drug targets at proteomic, phosphoproteomic, or genomic levels. The site is available at http://cprosite.ccr.cancer.gov. SignificanceAn interactive database for the expression and correlation for proteins, proteomic phosphorylations, and mRNA levels has been developed for analyzing the molecular alterations between tumors and normal tissues of various tumor types.

bioinformatics↗

bioRxiv2023

High-resolution structure of mouse radial spoke and its in-situ structure in ependymal cilia revealed by cryo-EM and cryo-ET

Radial spokes (RS) transmit mechanochemical signals between the central pair (CP) and axonemal dynein arms to coordinate ciliary motility. However, the high-resolution structure of mammalian RS remains missing. Here, we present the high-resolution cryo-EM structure of mouse RS head-neck complex in both monomer and dimer forms and reveal the intrinsic dynamics of the dimer. We also map the genetic mutations related to primary ciliary dyskinesia and asthenospermia on the head-neck complex. Moreover, we present the unprecedented cryo-ET and sub-tomogram averaging map of mouse ependymal cilia, whose beating creates unidirectional cerebrospinal fluid flow, and build the models for RS1-3, IDAs, and N-DRC. Strikingly, our cryo-ET map reveals the lack of IDA-b/c/e and the absence of tektin filaments within the A-tubule of doublet microtubules in ependymal cilia compared with mammalian respiratory cilia and sperm flagella. This tissue-specific feature may represent an evolutionary choice driven by the functional requirements on ependymal cilia. Our findings reveal the RS head-neck assembly mechanism, shed light on the coordinated rigid and elastic RS-CP interaction modes beneficial for the regulation of asymmetric ciliary beating, and also facilitate understandings on the etiology of ciliary dyskinesia-related ciliopathies.

biophysics↗

bioRxiv2023

Neural assemblies coordinated by cortical waves are associated with waking and hallucinatory brain states

The relationship between sensory stimuli and perceptions is brain-state dependent: in wakefulness stimuli evoke perceptions; under anesthesia perceptions are abolished; during dreaming and in dissociated states, percepts are internally generated. Here, we exploit this state dependence to identify brain activity associated with internally generated or stimulus-evoked perception. In awake mice, visual stimuli phase reset spontaneous cortical waves to elicit 3-6 Hz feedback traveling waves. These stimulus-evoked waves traverse the cortex and entrain visual and parietal neurons. Under anesthesia and during ketamine-induced dissociation, visual stimuli do not disrupt spontaneous waves. Uniquely in the dissociated state, spontaneous waves traverse the cortex caudally and entrain visual and parietal neurons, akin to stimulus-evoked waves in wakefulness. Thus, coordinated neuronal assemblies orchestrated by traveling cortical waves emerge in states in which perception can manifest. The awake state is privileged in that this coordination is elicited by specifically by external visual stimuli.

neuroscience↗

bioRxiv2023

Exercise improved P2Y12-regulated microglial dynamics during stroke via endocannabinoid signaling

Microglia are vigilant housekeepers in the adult brain, they continually extend and retract their processes to survey their microenvironment. In a dependent manner involving P2Y12 receptors, microglia undergo morphological and functional changes to form microglia-neuron contacts to protect neurons from damage. By using in vivo two-photon imaging, we found that physical exercise (PE) upregulated microglial P2Y12 expression, increased microglial dynamics, and promoted the microglia contacting with neurons in a mouse model of transit middle cerebral artery occlusion (tMCAO). As a result, microglial processes inhibited neuronal calcium overloads, protected against damage of the neuronal mitochondria and synaptic structure. Inhibition of P2Y12 by PSB0739 abolished the protection induced by PE. Mechanistically, we found PE increased the cannabinoid receptor 2 (CBR2) in microglia, and administration of AM630, a CBR2 antagonist, decreased P2Y12R expression and abolished PE-mediated effects. These findings identified endocannabinoid signaling may as the critical regulator of the PE-induced P2Y12-mediated effect whereby PE increased the endocannabinoid system to regulate purinergic signaling, further inducing microglial processes at microglia-neuron contacts to monitor and protect neuronal functioning.

neuroscience↗

bioRxiv2023

Weakly supervised contrastive learning infers molecular subtypes and recurrence risk of breast cancer from pathology images

The deep learning-powered computational pathology has led to sig-nificant improvements in the speed and precise of tumor diagnosis,, while also exhibiting substantial potential to infer genetic mutations and gene expression levels. However,current studies remain limited in predicting molecular subtypes and recurrence risk in breast cancer. In this paper, we proposed a weakly supervised contrastive learning framework to address this challenge. Our framework first performed contrastive learning pretraining on large-scale unlabeled patches tiled from whole slide images (WSIs) to extract patch-level features. The gated attention mechanism was leveraged to aggregate patch-level features to produce slide feature that was then applied to various downstream tasks. To confirm the effectiveness of the proposed method, we have conducted extensive experiments on four independent cohorts of breast cancer. For gene expression prediction task, rather than one model per gene, we adopted multitask learning to infer the expression levels of 21 recurrence-related genes, and achieved remarkable performance and generalizability that were validated on an external cohort. Particularly, the predictive power to infer molecular subtypes and recurrence events was strongly validated by cross-cohort experiments. In addition, the learned patch-level attention scores enabled us to generate heatmaps that were highly consistent with pathologist annotations and spatial transcriptomic data. These findings demonstrated that our model effectively established the high-order genotype-phenotype associations, thereby enhances the potential of digital pathology in clinical applications.

bioinformatics↗

bioRxiv2023

Discovery of novel multi-functional peptides by using protein language models and graph-based deep learning

Functional peptides are one kind of short protein fragments that have a wide range of beneficial functions for living organisms. The majority of previous research focused on mono-functional peptides, but a growing number of multi-functional peptides have been discovered. Although enormous experimental efforts endeavor to assay multi-functional peptides, only a small fraction of millions of known peptides have been explored. Effective and precise techniques for identifying multi-functional peptides can facilitate their discovery and mechanistic understanding. In this article, we presented a novel method, called iMFP-LG, for identifying multi-functional peptides based on protein language models (pLMs) and graph attention networks (GATs). Comparison results showed iMFP-LG significantly outperforms state-of-the-art methods on both multifunctional bioactive peptides and multi-functional therapeutic peptides datasets. The interpretability of iMFP-LG was also illustrated by visualizing attention patterns in pLMs and GATs. Regarding to the outstanding performance of iMFP-LG on the identification of multi-functional peptides, we employed iMFP-LG to screen novel candidate peptides with both ACP and AMP functions from millions of known peptides in the UniRef90. As a result, 8 candidate peptides were identified, and 1 candidate that exhibits significant antibacterial and anticancer effect was confirmed through molecular structure alignment and biological experiments. We anticipate iMFP-LG can assist in the discovery of multi-functional peptides and contribute to the advancement of peptide drug design. Availability and implementationThe models and associated code are available at: https://github.com/chen-bioinfo/iMFP-LG. Supplementary informationSupplementary data are available online.

bioinformatics↗

bioRxiv2023

Origin and early divergence of tandem duplicated sorbitol transporter genes in Rosaceae

Sorbitol is a critical photosynthate and storage substance in the Rosaceae family. Sorbitol transporters (SOTs) play a vital role in facilitating sorbitol allocation from source to sink organs and sugar accumulation in sink organs. Despite observing gene duplications in the SOT gene family, the origin and evolutionary process of these duplications are unclear, due to the complicated interplay of whole genome duplications and tandem duplications. Here, we investigated the synteny relationships of all detected Polyol/Monosaccharide Transporter (PLT) genes in 61 angiosperm genomes and SOT genes in major representative Rosaceae genomes. Combining phylogenetic analysis, we elucidated the lineage-specific expansion and syntenic conservation of PLTs and SOTs across different plant lineages. We found that Rosaceae SOTs, as PLT family members, originated from a pair of PLT tandem duplicating genes belonging to Class III-A. Additionally, lineage-specific and synergistic duplications in Amygdaloideae had contributed to the expansion of SOTs in Rosaceae plants. Overall, our findings provide insights into the genomic origins, duplication, and divergence of SOT gene family members, which are fundamental for further functional characterizations of each member.

genomics↗

bioRxiv2023

A shared pathogenic mechanism for valproic acid and SHROOM3 knockout in a brain organoid model of neural tube defects

Neural tube defects (NTDs) including anencephaly and spina bifida are common major malformations of fetal development resulting from incomplete closure of the neural tube. These conditions lead to either universal death (anencephaly) or life-long severe complications (spina bifida). Despite hundreds of genetic mouse models having neural tube defect phenotypes, the genetics of human NTDs are poorly understood. Furthermore, pharmaceuticals such as antiseizure medications have been found clinically to increase the risk of NTDs when administered during pregnancy. Therefore, a model that recapitulates human neurodevelopment would be of immense benefit to understand the genetics underlying NTDs and identify teratogenic mechanisms. Using our self-organizing single rosette spheroid (SOSRS) brain organoid system, we have developed a high-throughput image analysis pipeline for evaluating SOSRS structure for NTD-like phenotypes. Similar to small molecule inhibition of apical constriction, the antiseizure medication valproic acid (VPA), a known cause of NTDs, increases the apical lumen size and apical cell surface area in a dose-responsive manner. This expansion was mimicked by GSK3{beta} and HDAC inhibitors; however, RNA sequencing suggests VPA does not inhibit GSK3{beta} at these concentrations. Knockout of SHROOM3, a well-known NTD-related gene, also caused expansion of the lumen as well as reduced f-actin polarization. The increased lumen sizes were caused by reduced cell apical constriction suggesting that impingement of this process is a shared mechanism for VPA treatment and SHROOM3-KO, two well-known causes of NTDs. Our system allows the rapid identification of NTD-like phenotypes for both compounds and genetic variants and should prove useful for understanding specific NTD mechanisms and predicting drug teratogenicity.

neuroscience↗

bioRxiv2023

C. elegans males optimize mate-choice decisions via sex-specific responses to multimodal sensory cues

For sexually reproducing animals, selecting optimal mates is essential for maximizing reproductive fitness. Because the nematode C. elegans reproduces mostly by self-fertilization, little is known about its mate-choice behaviors. While several sensory cues have been implicated in males ability to recognize hermaphrodites, achieving an integrated understanding of the ways males use these cues to assess relevant characteristics of potential mates has proven challenging. Here, we use a choice-based social-interaction assay to explore the ability of C. elegans males to make and optimize mate choices. We find that males use a combination of volatile sex pheromones (VSPs), ascaroside pheromones, surface-bound chemical cues, and other signals to robustly assess a variety of features of potential mates. Specific aspects of mate choice are communicated by distinct signals: the presence of a sperm-depleted, receptive hermaphrodite is likely signaled by VSPs, while developmental stage and sex are redundantly specified by ascaroside pheromones and surface-associated cues. Ascarosides also signal nutritional information, allowing males to choose well-fed over starved mates, while both ascarosides and surface-associated cues cause males to prefer virgin over previously mated hermaphrodites. The male-specificity of these behavioral responses is determined by both male-specific neurons and the male state of sex-shared circuits, and we reveal an unexpected role for the sex-shared ASH sensory neurons in male attraction to endogenously produced hermaphrodite ascarosides. Together, our findings lead to an integrated view of the signaling and behavioral mechanisms by which males use diverse sensory cues to assess multiple features of potential mates and optimize mate choice.

neuroscience↗

bioRxiv2023

The BTB-ZF gene Bm-mamo regulate pigmentation in caterpillars

The color pattern of insects is one of the most diverse adaptive evolutionary phenotypes. However, the molecular regulation of this color pattern is not fully understood. In this study, we found that the transcription factor Bm-mamo is responsible for black dilute (bd) allele mutations in the silkworm. Bm-mamo belongs to the BTB zinc finger family and is orthologous to mamo in Drosophila melanogaster. This gene has a conserved function in gamete production in Drosophila and silkworms and has evolved a pleiotropic function in the regulation of color patterns in caterpillars. Using RNAi and clustered regularly interspaced short palindromic repeats (CRISPR) technology, we showed that Bm-mamo is a repressor or has dark melanin patterns in the larval epidermis. Using in vitro binding assays and gene expression profiling in wild-type and mutant larvae, we also showed that Bm-mamo likely regulates the expression of related pigment synthesis and cuticular protein genes in a coordinated manner to mediate its role in color pattern formation. This mechanism is consistent with the dual role of this transcription factor in regulating both the structure and shape of the cuticle and the pigments that are embedded within it. This study provides new insight into the regulation of color patterns as well as into the construction of more complex epidermis features in some insects.

genetics↗

bioRxiv2023

A single neuron in C. elegans orchestrates multiple motor outputs through parallel modes of transmission

Animals generate a wide range of highly coordinated motor outputs, which allows them to execute purposeful behaviors. Individual neuron classes in the circuits that generate behavior have a remarkable capacity for flexibility, as they exhibit multiple axonal projections, transmitter systems, and modes of neural activity. How these multi-functional properties of neurons enable the generation of highly coordinated behaviors remains unknown. Here we show that the HSN neuron in C. elegans evokes multiple motor programs over different timescales to enable a suite of behavioral changes during egg-laying. Using HSN activity perturbations and in vivo calcium imaging, we show that HSN acutely increases egg-laying and locomotion while also biasing the animals towards low-speed dwelling behavior over longer timescales. The acute effects of HSN on egg-laying and high-speed locomotion are mediated by separate sets of HSN transmitters and different HSN axonal projections. The long-lasting effects on dwelling are mediated by HSN release of serotonin that is taken up and re-released by NSM, another serotonergic neuron class that directly evokes dwelling. Our results show how the multi-functional properties of a single neuron allow it to induce a coordinated suite of behaviors and also reveal for the first time that neurons can borrow serotonin from one another to control behavior.

neuroscience↗