Biology subjects

Yang, E.

Publications and source records attributed to Yang, E..

At least 55 records · Page 3Linked to original sources

bioRxiv2024

Anatomical and functional analysis of the corticospinal tract in an FRDA mouse model

Friedreichs ataxia (FRDA) is one of the most common hereditary ataxias. It is caused by a GAA repeat in the first intron of the FXN gene, which encodes an essential mitochondrial protein. Patients suffer from progressive motor dysfunction due to the degeneration of mechanoreceptive and proprioceptive neurons in dorsal root ganglia (DRG) and cerebellar dentate nucleus neurons, especially at early disease stages. Postmortem analyses of FRDA patients also indicate pathological changes in motor cortex including in the projection neurons that give rise to the cortical spinal tract (CST). Yet, it remains poorly understood how early in the disease cortical spinal neurons (CSNs) show these alterations, or whether CSN/CST pathology resembles the abnormalities observed in other tissues affected by FXN loss. To address these questions, we examined CSN driven motor behaviors and pathology in the YG8JR FRDA mouse model. We find that FRDA mice show impaired motor skills, exhibit significant reductions in CSN functional output, and, among other pathological changes, show abnormal mitochondrial distributions in CSN neurons and CST axonal tracts. Moreover, some of these alterations were observed as early as two months of age, suggesting that CSN/CST pathology may be an earlier event in FRDA disease than previously appreciated. These studies warrant a detailed mechanistic understanding of how FXN loss impacts CSN health and functionality.

neuroscience↗

bioRxiv2024

Layer Va neurons, as major presynaptic partners of corticospinal neurons, play critical roles in skilled movements

Corticospinal neurons (CSNs) are located in the cortex and projecting into the spinal cord. The activation of CSNs, which is associated with skilled motor behaviors, induces the activation of interneurons in the spinal cord. Eventually, motor neuron activation is induced by corticospinal circuits to coordinate muscle activation. Therefore, elucidating how the activation of CSNs in the brain is regulated is necessary for understanding the roles of CSNs in skilled motor behaviors. However, the presynaptic partners of CSNs in the brain remain to be identified. Here, we performed transsynaptic rabies virus-mediated brain-wide mapping to identify presynaptic partners of CSNs (pre-CSNs). We found that pre-CSNs are located in all cortical layers, but major pre-CSNs are located in layer Va. A small population of pre-CSNs are also located outside the cortex, such as in the thalamus. Inactivation of layer Va neurons in Tlx3-Cre mice results in deficits in skilled reaching and grasping behaviors, suggesting that, similar to CSNs, layer Va neurons are critical for skilled movements. Finally, we examined whether the connectivity of CSNs is altered after spinal cord injury (SCI). We found that unlike connections between CNSs and postsynaptic neurons, connections between pre-CSNs and CSNs do not change after SCI.

neuroscience↗

bioRxiv2024

The Genomes of Nematode-Trapping Fungi Provide Insights into the Origin and Diversification of Fungal Carnivorism

Nematode-trapping fungi (NTF), most of which belong to a monophyletic lineage in Ascomycota, cannibalize nematodes and other microscopic animals, raising questions regarding the types and mechanisms of genomic changes that enabled carnivorism and adaptation to the carbon-rich and nitrogen-poor environment created by the Permian-Triassic extinction event. Here, we conducted comparative genomic analyses of 21 NTF and 21 non-NTF to address these questions. Carnivorism-associated changes include expanded genes for nematode capture, infection, and consumption (e.g., adhesive proteins, CAP superfamily, eukaryotic aspartyl proteases, and serine-type peptidases). Although the link between secondary metabolite (SM) production and carnivorism remains unclear, we found that the numbers of SM gene clusters among NTF are significantly lower than those among non-NTF. Significantly expanded cellulose degradation gene families (GH5, GH7, AA9, and CBM1) and contracted genes for carbon-nitrogen hydrolases (enzymes that degrade organic nitrogen to ammonia) are likely associated with adaptation to the carbon-rich and nitrogen-poor environment. Through horizontal gene transfer events from bacteria, NTF acquired the Mur gene cluster (participating in synthesizing peptidoglycan of the bacterial cell wall) and Hyl (a virulence factor in animals). Disruption of MurE reduced NTFs ability to attract nematodes, supporting its role in carnivorism. This study provides new insights into how NTF evolved and diversified after the Permian-Triassic mass extinction event.

evolutionary biology↗

bioRxiv2023

New germline Cas9 promoters show improved performance for homing gene drive

Gene drive systems could be a viable strategy to prevent pathogen transmission or suppress vector populations by propagating drive alleles with super-Mendelian inheritance. CRISPR-based homing gene drives, perhaps the most powerful gene drive strategy, convert wild type alleles into drive alleles in heterozygotes with the help of Cas9 and gRNA. However, achieving successful outcomes with these drives often requires high performance. Specifically, it is desirable to identify Cas9 promoters that yield high drive conversion rates, minimize the formation rate of resistance alleles in both the germline and the early embryo, and limit somatic Cas9 expression. Thus far, high-performance promoters have only been discovered in Anopheles species. In Drosophila, the nanos promoter avoids leaky somatic expression, but at the cost of high embryo resistance from maternally deposited Cas9. To improve drive efficiency, we tested eleven Drosophila melanogaster germline promoters in several configurations. Some of the new promoters achieved higher drive conversion efficiency with minimal embryo resistance, but none could completely avoid somatic expression like nanos. However, such somatic expression often did not carry detectable fitness costs when the promoter-Cas9 elements supported a rescue homing drive targeting a haplolethal gene, suggesting somatic drive conversion. Based on our findings, we selected two Cas9 promoter lines for cage experiments with a 4-gRNA suppression drive. While one promoter exhibited substantial somatic effects, leading to a low drive equilibrium frequency, the other outperformed nanos, resulting in the successful suppression of the cage population. Overall, these novel Cas9 promoters hold potential advantages for homing drives in Drosophila species and may also possess valuable homologs in other organisms.

genetics↗

bioRxiv2023

Hierarchical design of pseudosymmetric protein nanoparticles

Discrete protein assemblies ranging from hundreds of kilodaltons to hundreds of megadaltons in size are a ubiquitous feature of biological systems and perform highly specialized functions 1-3. Despite remarkable recent progress in accurately designing new self-assembling proteins, the size and complexity of these assemblies has been limited by a reliance on strict symmetry 4,5. Inspired by the pseudosymmetry observed in bacterial microcompartments and viral capsids, we developed a hierarchical computational method for designing large pseudosymmetric self-assembling protein nanomaterials. We computationally designed pseudosymmetric heterooligomeric components and used them to create discrete, cage-like protein assemblies with icosahedral symmetry containing 240, 540, and 960 subunits. At 49, 71, and 96 nm diameter, these nanoparticles are the largest bounded computationally designed protein assemblies generated to date. More broadly, by moving beyond strict symmetry, our work represents an important step towards the accurate design of arbitrary self-assembling nanoscale protein objects.

bioengineering↗

bioRxiv2023

Unraveling the dynamic transcriptomic changes during the dimorphic transition of Talaromyces marneffei through time-course analysis

Systemic dimorphic fungi pose a significant public health challenge, causing over one million new infections annually. The dimorphic transition between saprophytic mycelia and pathogenic yeasts is strongly associated with the pathogenesis of dimorphic fungi. However, despite the dynamic nature of dimorphic transition, the current omics studies focused on dimorphic transition primarily employ static strategies, partly due to the lack of suitable dynamic analytical methods. Here, we firstly conducted time-course transcriptional profiling during the dimorphic transition of Talaromyces marneffei, a model organism for thermally dimorphic fungi. Then, we identified 5,223 dimorphic transition induced genes (DTIGs) by developing DyGAM-NS (dynamic optimized generalized additive model with natural cubic smoothing), a model that enables the capture of non-uniform and nonlinear transcriptional changes during intricate biological processes. Notably, the DyGAM-NS outperformed other commonly used models, achieving the highest F1-score in DTIGs identification. The cluster analysis of DTIGs suggests differential functional involvement of genes at distinct stages of dimorphic transition. Moreover, we observed divergent gene expression patterns between mycelium-to-yeast and yeast-to-mycelium transitions, indicating the asymmetrical nature of two transition directions. Additionally, leveraging the identified DTIGs, we constructed a regulatory network for the dimorphic transition and identified two zinc finger-containing transcription factors that potentially regulate dimorphic transition in T. marneffei. In summary, our study not only elucidates the dynamic changes in transcriptional profiles during the dimorphic transition of T. marneffei but also provides a novel perspective for unraveling the underlying mechanisms of fungal dimorphism. IMPORTANCEThe dimorphic transition, i.e., morphological switch between saprophytic mycelia and pathogenic yeasts, plays a pivotal role in the pathogenesis of dimorphic fungi. However, the underlying mechanisms of dimorphic transition remain poorly understood, partly due to the lack of dynamic analytical methods suitable for its intricate nature. In the current study, we dissected the dynamic transcriptional profiles of dimorphic transition with a model thermally dimorphic fungus, T. marneffei, by developing a novel analytical method, DyGAM-NS. We proved that DyGAM-NS was more powerful in capturing the non-uniform and nonlinear gene expression variations during the dimorphic transition. With DyGAM-NS, we identified a repertoire of genes associated with dimorphic transition, and comprehensively unraveled distinct functions and expression patterns at different transition stages of T. marneffei, which offers novel perspectives regarding the mechanistic underpinnings of fungal dimorphism.

microbiology↗

bioRxiv2023

Whole body cell map tracks tissue-specific immune cell accumulation and plasticity loss through ageing

Understanding tissue biologys heterogeneity is crucial for advancing precision medicine. Despite the centrality of the immune system in tissue homeostasis, a detailed and comprehensive map of immune cell distribution and interactions across human tissues and demographics remains elusive. To fill this gap, we harmonised data from 12,981 single-cell RNA sequencing samples and curated 29 million cells from 45 anatomical sites to create a comprehensive compositional and transcriptional healthy map of the healthy immune system. We used this resource and a novel multilevel modelling approach to track immune ageing and test differences across sex and ethnicity. We uncovered conserved and tissue-specific immune-ageing programs, resolved sex-dependent differential ageing and identified ethnic diversity in clinically critical immune checkpoints. This study provides a quantitative baseline of the immune system, facilitating advances in precision medicine. By sharing our immune map, we hope to catalyse further breakthroughs in cancer, infectious disease, immunology and precision medicine.

immunology↗

bioRxiv2023

FluoMALDI microscopy: matrix co-crystallization simultaneously enhances fluorescence and MALDI imaging

We report that co-crystallization of fluorophores with matrix-assisted laser desorption/ionization (MALDI) imaging matrices significantly enhances fluorophore brightness up to 79-fold, enabling the amplification of innate tissue autofluorescence. This discovery facilitates FluoMALDI, the imaging of the same biological sample by both fluorescence microscopy and MALDI imaging. Our approach combines the high spatial resolution and specific labeling capabilities of fluorescence microscopy with the inherently multiplexed, versatile imaging capabilities of MALDI imaging. This new paradigm eliminates the notion that MALDI matrices obscure and obstruct optical microscopy approaches, allowing to image the exact same cells in tissues, free of any physical changes between fluorescence and MALDI imaging, which minimizes data registration processes. Matrix-fluorophore co-crystallization also facilitates applications with insufficient fluorescence brightness. We showcase the capabilities of FluoMALDI imaging with endogenous and exogenous fluorophores and autofluorescence-based FluoMALDI of brain and kidney tissue sections. FluoMALDI will advance structural-functional microscopic imaging in cell biology, biomedicine, and pathology.

biochemistry↗

bioRxiv2023

Tumor-specific neutrophils originating from meninges promote glioblastoma

Glioma is one of the most aggressive human cancers with limited therapeutic options. Though research has extensively examined immune components in those malignant tumors, the pathophysiological mechanism establishing their immunosuppressive microenvironment remains incompletely characterized. In this study, we report for the first time the unique presence of tumor-specific neutrophils (TSNs) in human glioblastoma (GBM) tumors. This newly defined neutrophil subtype exhibits the high expression of several immunosuppressive genes (e.g., CD274 and IDO1) and is strongly correlated with glioma grades and poor prognosis of patients. TSNs with comparable gene signatures are similarly present in the tumors but not bone marrow or spleen of mouse glioma models. Blockage of TSN recruitment by either Cxcl1-knockout in glioma cells or Cxcr2-deletion in host mice significantly enhances antitumor immunity and inhibits tumor progression. Surprisingly, we further identify the meninges as the key extratumoral source of generating TSNs in both human GBM patients and mouse glioma models. These results have elucidated a novel mechanism of neutrophils designating the tumor immune microenvironment and the essential link of meningeal immunity to glioma.

cancer biology↗

bioRxiv2023

Charting the cellular biogeography in colitis reveals fibroblast trajectories and coordinated spatial remodeling

Gut inflammation involves contributions from immune and non-immune cells, whose interactions are shaped by the spatial organization of the healthy gut and its remodeling during inflammation. The crosstalk between fibroblasts and immune cells is an important axis in this process, but our understanding has been challenged by incomplete cell-type definition and biogeography. To address this challenge, we used MERFISH to profile the expression of 940 genes in 1.35 million cells imaged across the onset and recovery from a mouse colitis model. We identified diverse cell populations; charted their spatial organization; and revealed their polarization or recruitment in inflammation. We found a staged progression of inflammation-associated tissue neighborhoods defined, in part, by multiple inflammation-associated fibroblasts, with unique expression profiles, spatial localization, cell-cell interactions, and healthy fibroblast origins. Similar signatures in ulcerative colitis suggest conserved human processes. Broadly, we provide a framework for understanding inflammation-induced remodeling in the gut and other tissues.

immunology↗

bioRxiv2023

RaMALDI: enabling simultaneous Raman and MALDI imaging of the same tissue section

Multimodal tissue imaging techniques that integrate two complementary modalities are powerful discovery tools for unraveling biological processes and identifying biomarkers of disease. Combining Raman spectroscopic imaging (RSI) and matrix-assisted laser-desorption/ionization (MALDI) mass spectrometry imaging (MSI) to obtain fused images with the advantages of both modalities has the potential of providing spatially resolved, sensitive, and specific biomolecular information, but has so far involved two separate, consecutive tissue sections for RSI and MALDI MSI, resulting in images from two separate entities with inherent disparities. We have developed RaMALDI, a streamlined, integrated, multimodal imaging workflow of RSI and MALDI MSI, performed on a single tissue section with one sample preparation protocol. We show that RaMALDI imaging of various tissues effectively integrates molecular information acquired from both RSI and MALDI MSI of the same sample. Table of Contents O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=142 SRC="FIGDIR/small/539107v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@1829ccaorg.highwire.dtl.DTLVardef@3d018org.highwire.dtl.DTLVardef@531015org.highwire.dtl.DTLVardef@144f1a3_HPS_FORMAT_FIGEXP M_FIG C_FIG We demonstrate for the first time RaMALDI imaging, a streamlined, integrated multimodal imaging workflow of Raman spectroscopy imaging (RSI) and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI), which is performed on a single sample and uses one sample preparation protocol. RaMALDI imaging of various tissues effectively integrates molecular information acquired from both RSI and MALDI MSI of the same sample.

bioengineering↗

bioRxiv2023

mEMbrain: an interactive deep learning MATLAB tool for connectomic segmentation on commodity desktops

Connectomics is fundamental in propelling our understanding of the nervous systems organization, unearthing cells and wiring diagrams reconstructed from volume electron microscopy (EM) datasets. Such reconstructions, on the one hand, have benefited from ever more precise automatic segmentation methods, which leverage sophisticated deep learning architectures and advanced machine learning algorithms. On the other hand, the field of neuroscience at large, and of image processing in particular, has manifested a need for user-friendly and open source tools which enable the community to carry out advanced analyses. In line with this second vein, here we propose mEMbrain, an interactive MATLAB-based software which wraps algorithms and functions that enable labeling and segmentation of electron microscopy datasets in a user-friendly user interface compatible with Linux and Windows. Through its integration as an API to the volume annotation and segmentation tool VAST, mEMbrain encompasses functions for ground truth generation, image preprocessing, training of deep neural networks, and on-the-fly predictions for proofreading and evaluation. The final goals of our tool are to expedite manual labeling efforts and to harness MATLAB users with an array of semi-automatic approaches for instance segmentation. We tested our tool on a variety of datasets that span different species at various scales, regions of the nervous system and developmental stages. To further expedite research in connectomics, we provide an EM resource of ground truth annotation from 4 different animals and 5 datasets, amounting to around 180 hours of expert annotations, yielding more than 1.2 GB of annotated EM images. In addition, we provide a set of 4 pre-trained networks for said datasets. All tools are available from https://lichtman.rc.fas.harvard.edu/mEMbrain/. With our software, our hope is to provide a solution for lab-based neural reconstructions which does not require coding by the user, thus paving the way to affordable connectomics.

neuroscience↗

bioRxiv2022

Predicting individualized tissue gene expression profiles with multi-task learning

Predicting tissue expression profiles from peripheral surrogate samples, especially blood transcriptome, has become an effective alternative when invasive procedures are not ideal. However, existing approaches ignore tissue-shared intrinsic relevance, inevitably limiting predictive performance. Here, we propose a unified deep learning-based multi-task learning framework, Multi-tissue Transcriptome Mapping (MTM), enabling the prediction of individualized expression profiles from any available tissue of an individual. By jointly leveraging individualized cross-tissue information through multi-task learning, MTM achieves superior sample-level and gene-level performance. With the high prediction accuracy and the ability to preserve individualized biological variations, MTM could facilitate both fundamental and clinical biomedical research.

bioinformatics↗

bioRxiv2022

Bringing language to dynamic brain states: the default network dominates neural responses to evolving movie stories

Naturalistic neuroscience opened the door to new insights into neural circuits that serve real-world dynamic perception. Such studies have often neglected the rich texture of the movie narrative itself, but semantic content can be used to contextualize the induced neural responses. Here, we translated natural language processing tools from machine learning to characterize brain states estimated from hidden Markov models. Our analytical strategy allowed pitting shallow unimodal against the deep associative brain network layers in explaining how semantic content of the movie links to observed neural activity. Pooling information across >53,000 brain image time points watching Forrest Gump, we could show that distinct dynamic brain states capture unique semantic facets along the unfolding movie narrative. The spatiotemporal dynamics of brain states explicitly captured subject-level responses throughout the brain network hierarchy. Across all analyses, the default network was most intimately linked to semantic information integration, and this neural system switched online for longest durations during movie watching. Further, we identified and described two mechanisms of how the default network liaises dynamically with microanatomically defined subregion partners: the amygdala and the hippocampus. Our study thus unlocks the potential of natural language processing to explore neural processes in everyday life situations that engage key aspects of conscious awareness.

neuroscience↗

bioRxiv2022

Stem Cell Secretome Promotes Scarless Corneal Wound Healing and Rescues Corneal Sensory Nerves

Corneal scarring is a leading cause of blindness in the world. In this study, we explored the therapeutic potential of corneal stromal stem cell (CSSC)-derived secretome in a mechanical debridement mouse model of corneal scarring. CSSC secretome was able to promote scarless corneal wound healing. The mechanisms include 1) dampening inflammation with reduced CD45+, CD11b+/GR1+, and CD11b+/F4/80+ inflammatory cells in the wounded corneas; 2) reducing fibrotic extracellular matrix deposition such as collagen IV, collagen 3A1, SPARC, and -SMA; 3) rescuing sensory nerves. The proteomic analysis shows upregulated proteins related to wound healing and cell adhesion which boost scarless wound healing. It also shows upregulated neuroprotective proteins in CSSC secretome related to axon guidance, neurogenesis, neuron projection development, and neuron differentiation. Four unique complement inhibitory proteins CD59, vitronectin, SERPING1, and C1QBP found in CSSC secretome contribute to reducing a complement cascade mediating cell death and membrane attacking complex autoantibodies after corneal injury. This study provides novel insights into mechanisms of stem cell secretome induced scarless corneal wound healing and neuroprotection and identifies regenerative proteins in the CSSC secretome. Significance StatementIn this study, we report the therapeutic role of corneal stromal stem cell (CSSC) secretome for scarless corneal wound healing and corneal sensory nerve rescuing. We uncovered that CSSC secretome dampens inflammation, reduces fibrosis, induces sensory nerve regeneration, and rescues corneal cells by inhibiting the complement system in the wounded mouse corneas. This study provides pre-clinical evidence for the use of CSSC secretome as a biologic treatment for corneal scarring to prevent corneal blindness. We delineated a plethora of proteins in the CSSC secretome, which individually or in combination have the potential as future therapies for scarless corneal wound healing.

cell biology↗

bioRxiv2022

Substrate trapping approach identifies TRIM25 ubiquitination targets involved in diverse cellular and antiviral processes

The tripartite motif (TRIM) family of E3 ubiquitin ligases is well known for its roles in antiviral restriction and innate immunity regulation, in addition to many other cellular pathways. In particular, TRIM25-mediated ubiquitination affects both carcinogenesis and antiviral response. While individual substrates have been identified for TRIM25, it remains unclear how it regulates diverse processes. Here we characterized a mutation, R54P, critical for TRIM25 catalytic activity, which we successfully utilized to "trap" substrates. We demonstrated that TRIM25 targets proteins implicated in stress granule formation (G3BP1/2), nonsense-mediated mRNA decay (UPF1), and nucleoside synthesis (NME1). R54P abolishes TRIM25 inhibition of alphaviruses independently of the host interferon response, suggesting that this antiviral effect is a direct consequence of ubiquitination. Consistent with that, we observed diminished antiviral activity upon knockdown of several TRIM25-R54P specific interactors including NME1. Our findings highlight that multiple substrates mediate the cellular and antiviral activities of TRIM25, illustrating the multi-faceted role of this ubiquitination network in diverse biological processes.

cell biology↗

bioRxiv2022

Rhamnan Sulfate Reduces Atherosclerotic Plaque Formation and Vascular Inflammation

ObjectiveWhile lipid-lowering drugs have become a mainstay of clinical therapy these treatments only slow the progression of the disease and can have side effects. Thus, new treatment options are needed to supplement the effects of lipid lowering therapy for treating atherosclerosis. We examined the use of an inexpensive and widely available marine polysaccharide rhamnan sulfate as an oral therapeutic for limiting vascular inflammation and atherosclerosis. Methods and ResultsWe found rhamnan sulfate enhanced the barrier function of endothelial cells, preventing the deposition of LDL and maintaining barrier function even in the presence of glycocalyx-degrading enzymes. Rhamnan sulfate was also found to bind directly to FGF-2, PDGF-BB and NF-{kappa}B subunits with high affinity. In addition, rhamnan sulfate was a potent inhibitor of NF-{kappa}B pathway activation in endothelial cells by TNF-. We treated ApoE-/- mice with a high fat diet for 4 weeks and then an addition 9 weeks of high fat diet with or without rhamnan sulfate. Rhamnan sulfate reduced vascular inflammation and atherosclerosis in both sexes of ApoE-/- mice but had a stronger therapeutic effect in female mice. Oral consumption of rhamnan sulfate induced a significant decrease in cholesterol plasma levels in female mice but not in male mice. ConclusionsRhamnan sulfate has beneficial effects in reducing inflammation, binding growth factors and NF-{kappa}B, enhancing endothelial barrier function and reducing atherosclerotic plaque formation in ApoE-/- mice.

physiology↗

bioRxiv2022

Neural mechanism of acute stress management by trace aminergic signalling in the lateral habenula

Stress management is a prerequisite for the survival of vertebrates because chronic stress may cause depression and is known to negatively modulate the dopaminergic reward system1. Enhanced excitability of neurons in the lateral habenula (LHb) induced by chronic stress is essential for silencing dopaminergic neurons in the ventral tegmental area (VTA) via GABAergic neurons in the rostromedial tegmental nucleus (RMTg)2-10. However, the effect of acute stress on the LHb-RMTg-VTA pathway is unknown11-14. Here, we show that both aromatic L-amino acid decarboxylase (AADC)-expressing neurons (D-neurons)15 in the LHb and dopaminergic neurons in the VTA are activated by acute stress, whereas GABAergic neurons in the RMTg are not. Selective stimulation of LHb D-neurons and AADC knockdown of these neurons reverse-regulate the RMTg-VTA pathway. Circuit tracing and electrophysiology data demonstrate that trace aminergic signalling by LHb D-neurons directly suppresses RMTg GABAergic neurons. Furthermore, local activation of trace amine-associated receptor 1 (TAAR1; a trace amine receptor) in the RMTg is sufficient to rescue the despair-like behaviour produced by the loss of AADC expression. Our results identify a novel efferent pathway from the LHb to the RMTg whereby trace aminergic signalling allows the brain to manage acute stress by preventing VTA dopaminergic neuron hypoactivity. The TAAR1-mediated trace aminergic signalling in the LHb-RMTg pathway may hold promise as a therapeutic target for stress-mediated psychological diseases.

neuroscience↗