Biology subjects

Hu, S.

Publications and source records attributed to Hu, S..

At least 73 records · Page 4Linked to original sources

bioRxiv2024

Genomic diversity and underlying metabolic variations of the human gut microbiome between populations at single nucleotide resolution

BackgroundA comprehensive and representative reference database is crucial for accurate taxonomic and functional profiling of the human gut microbiome in population-level studies. However, with 70% of current microbial reference data derived from Europeans and the Americans, East Asia, especially China, remain underrepresented. MethodsWe constructed the human Gut Microbiome Reference (GMR), comprising 478,588 high-quality microbial genomes from Chinese (247,134) and non-Chinese (231,454) populations. Species-level clustering and protein annotations were performed to characterize microbial diversity and function. We further integrated novel genomes into taxonomic profiling database and validated the improvements using independent cohort data. ResultsThe GMR dataset spans 6,664 species, including 26.4% newly classified species, and encodes over 20 million unique proteins, with 47% lacking known functional annotations. Notably, we observed that 35.35% and 32.46% of species unique to Chinese and non-Chinese populations, respectively. For 2,145 species shared between populations, 74% of 304 species with balanced prevalence between populations exhibited population-specific phylogenetic stratification, involving health relevant functionalities such as antibiotic resistance. Integration of novel genomes into taxonomic improved population-level species profiling by up to 23% and uncovered replicable associations between novel species and host physiological traits. ConclusionsOur study largely expands the compositional and functional landscape of the human gut microbiome, providing a crucial resource for studying the role of gut microbiome for regional health disparities.

genomics↗

bioRxiv2024

Automated Tumor and FUS Lesion Quantification on Multi-frequency Harmonic Motion and B-mode Imaging Using a Multi-modality Neural Network

Harmonic Motion Imaging (HMI) is an ultrasound elasticity imaging method that measures the mechanical properties of tissue using amplitude-modulated acoustic radiation force (AM-ARF). By estimating tissues on-axis oscillatory motion, HMI-derived displacement images represent localized relative stiffness and can predict the tumor response to neoadjuvant chemotherapy (NACT) and monitor focused ultrasound (FUS) ablation therapy. Multi-frequency HMI (MF-HMI) excites tissue at various AM frequencies simultaneously, which allows for image optimization without prior knowledge of inclusion size and stiffness. However, challenges remain in size estimation as inconsistent boundary effects result in different perceived sizes across AM frequencies. Herein, we developed an automated tumor and FUS lesion quantification method using a transformer-based multi-modality neural network, HMINet. It was trained on 380 pairs of MF-HMI and B-mode images of phantoms and in vivo orthotopic breast cancer mice (4T1). Test datasets included phantoms (n = 32), in vivo 4T1 mice (n = 24), breast cancer patients (n = 16), and a FUS-induced lesion, with average segmentation accuracy (Dice Similarity Score) of 0.95, 0.86, 0.82, and 0.87, respectively. To increase the generalizability of HMINet, we applied a transfer learning strategy, i.e., fine-tuning the model using patient data. For NACT patients, the displacement ratios (DR) between the tumor and surrounding tissue were calculated based on HMINet-segmented boundaries to predict tumor response based on stiffness changes.

bioengineering↗

bioRxiv2024

Continual integration of single-cell multimodal data with MIRACLE

Single-cell sequencing technologies have revolutionized our understanding of cellular heterogeneity and facilitated the construction of multi-omics cell atlases via data integration. However, updating these atlases with new data conventionally requires reintegration of all data and is computationally intensive, hindering timely updates and dynamic adjustments in biological and medical research. To address this challenge, we present Multimodal Integration with Continual Learning (MIRACLE), a novel online learning framework for the adaptive and efficient integration of single-cell multimodal data. MIRACLE employs dynamic architectures and data rehearsal strategies to support continual learning, allowing diverse data to be integrated while minimizing information loss over time. Our evaluations demonstrate that MIRACLE achieves accurate online integration with reduced computational requirements, effectively updating and expanding atlases with new cross-tissue and cross-modal data, and precisely identifying novel cell types and transferring labels across datasets. MIRACLE provides an efficient and flexible tool for single-cell community to integrate, share and explore biological knowledge from single-cell multimodal data.

bioinformatics↗

bioRxiv2024

Hemifusomes and Interacting Proteolipid Nanodroplets: Formation of a Novel Cellular Organelle Complex

Within cells, vesicle fusion, scission, and the formation of intraluminal vesicles are critical processes that facilitate traffic, degradation, and recycling of cellular components, and maintenance of cellular homeostasis. Despite significant advancements in elucidating the molecular mechanisms that drive these dynamic processes, the direct in situ visualization of membrane remodeling intermediates remains challenging. Here, through the application of cryo-electron tomography in mammalian cells, we have identified a previously undescribed vesicular organelle complex with unique membrane topology: heterotypic hemifused vesicles that share extended hemifusion diaphragms (HDs) with a 42 nm proteolipid nanodroplet (PND) at their rim. We have termed these organelle complexes "hemifusomes". The HDs of hemifusomes exhibit a range of sizes and curvatures, including the formation of lens-shaped compartments encapsulated within the membrane bilayer. The morphological diversity of the lens-shaped vesicle aligns with a step-wise process of their intraluminal budding, ultimately leading to their scission and the generation of intraluminal vesicles. We propose that hemifusomes function as versatile platforms for protein and lipid sorting and as central hubs for the biogenesis of intraluminal vesicles and the formation of multivesicular bodies.

cell biology↗

bioRxiv2024

A smartphone-based genetically recombinant whole-cell biosensor for highly sensitive monitoring of polychlorinated biphenyls (PCBs)

Polychlorinated biphenyls (PCBs) are highly carcinogenic and persistent pollutants commonly found in ecosystems. Their complex congeners pose a huge challenge to instrumental analysis and ELISA methods, which prefer single and known targets. To overcome this limitation, here we developed an Escherichia coli whole-cell biosensor (WCB) for simultaneously detecting multiple PCB congeners. In this sensor, PCBs were firstly converted into hydroxylated PCBs (OH-PCBs) by bphAB degradation circuits, which then serve as high-affinity targets of transcriptional factor HbpRCBP6-based sensing pathways for sensitive response through extensive chassis screening. The resulting biosensor BL21(DE3)/HbpRCBP6-bphAB shows the lowest detection limits for 2-CBP (2-chlorobiphenyl) to date and can recognize various PCB homologues, including 3-CBP, 4-CBP, 2,3-diCBP and 2,2-diCBP, with detection limits of 0.06-1 M. Further investigation of the docking structure and binding energy reveal that HbpRCBP6 has a stronger affinity for OH-PCBs than for PCBs, indicating that the conversion of PCB by BphAB enzymes is a key step to improve the sensitivity of WCB. Subsequently, we developed an immobilized hydrogel WCB and a smartphone-based detection procedure to facilitate real-time and user-friendly PCB detection. This study will not only advance the biomonitoring of PCB contaminants but also provide an innovative strategy for developing metabolic pathway-sensing proteins combined biosensor. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=128 SRC="FIGDIR/small/601110v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@10772cdorg.highwire.dtl.DTLVardef@22699org.highwire.dtl.DTLVardef@1343c27org.highwire.dtl.DTLVardef@595859_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2024

Structural and functional analysis of the Nipah virus polymerase complex

Nipah virus (NiV) is a bat-borne, zoonotic RNA virus that is among the most pathogenic viruses known to humans. The NiV polymerase, which mediates viral genome replication and mRNA transcription, is a drug target. However, NiV polymerase structures were previously unavailable. We determined the cryo-EM structure of the NiV polymerase complex, comprising the large protein (L) and its associated co-factor (P), and performed structural, biophysical, and functional analyses of the NiV polymerase. The complex assembles with a long P tetrameric coiled-coil that is capped by a bundle of -helices that we show are likely dynamic in solution. Highly conserved zinc-binding modules in the capping domain and a large insert in the RdRp palm domain that is short or absent in most other non-segmented negative strand RNA viruses are critical for replication and transcription. Our findings have the potential to aid in the rational development of drugs to combat NiV infection.

microbiology↗

bioRxiv2024

Therapeutic potential of SOX9 dysruption in Combined Hepatocellular Carcinoma-Cholangiocarcinoma

Combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) represents a challenging subtype of primary liver cancer with limited treatment options and a poor prognosis. Recently, we and others have highlighted the context-dependent roles of the biliary-specific transcription factor SOX9 in the pathogenesis of liver cancers using various Cre applications in Sox9(flox/flox) strains, to achieve elimination for exon 2 and 3 of the Sox9 gene locus as a preventive manner. Here, we reveal the contrasting responses of developmental Sox9 elimination using Alb-Cre;Sox9(flox/flox) (Sox9 LKO) versus CRISPR/Cas9-based tumor specific acute Sox9 CKO in SB-HDTVI-based Akt-YAP1 and Akt-NRAS cHCC-CCA formation. Sox9 LKO specifically abrogates the Akt-YAP1 CCA region while robustly stimulating the proliferation of remaining poorly differentiated HCC pertaining liver progenitor cell characteristics, whereas Sox9 CKO potently prevents Akt-YAP1 and Akt-NRAS cHCC-CCA development irrespective of fate of tumor cells compared to respective controls. Additionally, we find that Akt-NRAS, but not Akt-YAP1, tumor formation is partially dependent on the Sox9-Dnmt1 cascade. Pathologically, SOX9 is indispensable for Akt-YAP1-mediated HC-to-BEC/CCA reprogramming but required for the maintenance of CCA nodules. Lastly, therapeutic elimination of Sox9 using the OPN-CreERT2 strain combined with an inducible CRISPR/Cas9-based Sox9 iKO significantly reduces Akt-YAP1 cHCC-CCA tumor burden, similar to Sox9 CKO. Thus, we contrast the outcomes of acute Sox9 deletion with developmental Sox9 knockout models, emphasizing the importance of considering adaptation mechanisms in therapeutic strategies. This necessitates the careful consideration of genetic liver cancer studies using developmental Cre and somatic mutant lines, particularly for genes involved in hepatic commitment during development. Our findings suggest that SOX9 elimination may hold promise as a therapeutic approach for cHCC-CCA and underscore the need for further investigation to translate these preclinical insights into clinical applications.

cancer biology↗

bioRxiv2024

Characterizing interactions of ER resident proteins in situ through the YST-PPI method

The mutual interactions of ER resident proteins in the ER maintain its functions, prompting the protein folding, modification, and transportation. Here, a new method, named YST-PPI (YESS-based Split fast TEV protease System for Protein-protein Interaction) was developed, targeting the characterization of protein interactions in ER. YST-PPI method integrated the YESS system, split-TEV technology and endoplasmic reticulum retention signal peptide (ERS) to provide an effective strategy for studying ER in situ PPIs in a fast and quantitative manner. The interactions among 15 ER resident proteins of S. cerevisiae were explored using the YST-PPI system, and their interaction network map was constructed, in which more than 74 interacting resident protein pairs were identified. Our studies also showed that Lhs1p plays a critical role in regulating the interactions of most of the ER resident proteins, expect the Sil1p, indicating its potential role in controlling the ER molecular chaperones. Moreover, the mutual interaction revealed by our studies further confirmed that the ER resident proteins perform their functions in a synergetic way and multimer complex might be formed during the process.

microbiology↗

bioRxiv2024

Mucin-2 ER-to-Golgi transport mechanism identifies source of ER stress in inflammatory bowel disease

The intestinal mucous layer relies on mucin-2 secretion. While the mucin-2 secretory pathway has been studied, endoplasmic reticulum (ER) to Golgi apparatus (Golgi) trafficking remains poorly understood. The size of mucin-2 exceeds the capacity of regular coat protein complex II (COPII) vesicles, responsible for ER-to-Golgi transport. After confirming conventional secretion of mucin-2, we showed that COPII vesicle enlargement is facilitated by TANGO1 and cTAGE5, and promoted by KLHL12. Inflammatory bowel disease (IBD) is characterized by a compromised mucous layer, altered activity of Transforming Growth Factor {beta} (TGF-{beta}), and increased ER stress. Using a cell culture, we showed that TGF-{beta} inhibition induces TANGO1-mediated ER stress. Mucosal gene expression analysis in IBD patients confirmed elevated ER stress and validated concomitantly altered mRNA levels of TGF-{beta} with mucin-2 and transport proteins TANGO1 and cTAGE5. In conclusion, we propose that the unsuccessful formation of enlarged COPII vesicles could be a source of ER stress in IBD, because of lowered TANGO1 protein expression, subsequently leading to decreased mucin-2 secretion.

cell biology↗

bioRxiv2024

Jumbo phages possess independent synthesis and utilization systems of NAD+

Jumbo phages, phages with genomes >200 kbp, contain some unique genes for successful reproduction in their bacterial hosts. Due to complex and massive genomes analogous to those of small-celled bacteria, how do jumbo phages complete their life cycle remain largely undefined. In this study, we assembled 668 high-quality jumbo phage genomes from over 15 TB of intestinal metagenomic data from 955 samples of five animal species (cow, sheep, pig, horse, and deer). Within them, we obtained a complete genome of 716 kbp in length, which is the largest phage genome so far reported in the gut environments. Interestingly, 174 out of the 668 jumbo phages were found to encode all genes required for synthesis of NAD+ by the salvage pathway or Preiss-Handler pathway, referred as NAD-jumbo phage. Besides synthesis genes of NAD+, these NAD-jumbo phages also encode at least 15 types of NAD+-consuming enzyme genes involved in DNA replication, DNA repair, and counterdefense, suggesting that these phages not only have the capacity to synthesize NAD+ but also redirect NAD+ metabolism towards phage propagation need in hosts. Phylogenetic analysis and environmental survey indicated NAD-jumbo phages are widely present in the Earths ecosystems, including the human gut, lakes, salt ponds, mine tailings, and seawater. In summary, this study expands our understanding of the diversity and survival strategies of phages, and in-depth study of the NAD-jumbo phages is crucial for understanding their role in ecological regulation.

microbiology↗

bioRxiv2024

The Transcription Factor OsNAC5 Mediates Cadmium Stress Response and Accumulation in Rice

Cadmium (Cd) is a toxic heavy metal that endangers human health through contaminated rice consumption. Reducing Cd uptake in rice is essential for minimizing grain Cd accumulation. However, the transcriptional regulation of Cd uptake in rice remains largely elusive. This study reveals that the transcription factor OsNAC5 in Oryza sativa positively regulates the Cd transporter gene OsNRAMP1, influencing Cd uptake. OsNAC5 is primarily expressed in roots, localized to the nucleus, and upregulated by Cd-induced H2O2. Knocking out OsNAC5 reduces Cd levels in both shoots and roots and increases Cd sensitivity. OsNRAMP1 expression, enhanced by Cd stress, depends on OsNAC5, which binds to "CATGTG" motifs in the OsNRAMP1 promoter activating its expression. Loss of OsNAC5 function decreases Cd accumulation in rice grains. Our findings elucidate the transcriptional regulation of Cd stress response in rice and suggest biotechnological approaches to reduce Cd uptake in crops. Declaration of Competing InterestThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

plant biology↗

bioRxiv2024

Mechanical forces pattern endocardial Notch activation via mTORC2-PKC pathway

Notch signaling has been identified as a key regulatory pathway in patterning the endocardium through activation of endothelial-to-mesenchymal transition (EMT) in the atrioventricular canal (AVC) and proximal outflow tract (OFT) region. However, the precise mechanism underlying Notch activation remains elusive. By transiently blocking the heartbeat of E9.5 mouse embryos, we found that Notch activation in the arterial endothelium was dependent on its ligand Dll4, whereas the reduced expression of Dll4 in the endocardium led to a ligand-depleted field, enabling Notch to be specifically activated in AVC and OFT by regional increased shear stress. The strong shear stress altered the membrane lipid microdomain structure of endocardial cells, which activated mTORC2 and PKC and promoted Notch1 cleavage even in the absence of strong ligand stimulation. These findings highlight the role of mechanical forces as a primary cue for endocardial patterning and provide insights into the mechanisms underlying congenital heart diseases of endocardial origin.

developmental biology↗

bioRxiv2024

Distinct roles of Nrf1 and Nrf2 in coordinately controlling the anti-ageing response

Cellular senescence has been accepted as a fundamental contributor to ageing and a variety of age-related diseases, in which oxidative stress has been further recognized to play a critical initiation role. However, the anti-senescence potential of antioxidant nuclear factor erythroid-derived 2-like 1 (Nrf1, encoded by Nfe2l1) remains elusive to date, even though the hitherto accumulating evidence demonstrates that it is an indispensable redox-determining transcription factor for maintaining cellular homeostasis and organ integrity. Herein, we discovered that deletion of Nrf1 resulted in markedly elevated senescence characteristics in Nrf1-/- cells, as characterized by two distinct experimental models induced by oxidative stress, which are evinced by typically heightened activity of senescence-associated {beta}-galactosidase and progressive senescence-associated secretory phenotype (SASP), along with decreased cell vitality and intensified cell cycle arrest. Further experimental investigation also uncovered that such acceleration of oxidative stress-induced senescence resulted from heightened disturbance in the cellular homeostasis, because deficiency of Nrf1 leads to the STAG2- and SMC3-dependent chromosomal stability disruption and autophagy dysfunction, though as accompanied by excessive accumulation of Nrf2 (encoded by Nfe2l2). The aberrant hyperactive Nrf2 cannot effectively counteract the escalating disturbance of cellular homeostasis caused by Nrf1-/-. Overall, this study has provided a series of evidence supporting that Nrf1 indeed exerts an essential protective function against oxidative stress-induced cellular senescence, thereby, highlighting its primary indispensable contribution to maintaining robust cell homeostasis.

biochemistry↗

bioRxiv2024

Structural basis of Ebola virus nucleocapsid assembly and functions

The Ebola virus, a member of the Filoviridae family, causes severe hemorrhagic fever in humans. Filamentous virions contain a helical nucleocapsid responsible for genome transcription, replication, and packaging into progeny virions. The nucleocapsid consists of a helical nucleoprotein (NP)-viral genomic RNA complex forming the core structure, to which VP24 and VP35 bind externally. Two NPs, each paired with a VP24 molecule, constitute a repeating unit. However, the detailed nucleocapsid structure remains unclear. Here, we determined the nucleocapsid-like structure within virus-like particles at 4.6 [A] resolution using single-particle cryo-electron microscopy. Mutational analysis identified specific interactions between the two NPs and two VP24s and demonstrated that each of the two VP24s in different orientations distinctively regulates nucleocapsid assembly, viral RNA synthesis, and intracellular transport of the nucleocapsid. Our findings highlight the sophisticated mechanisms underlying the assembly and functional regulation of the nucleocapsid and provide insights into antiviral development.

microbiology↗

bioRxiv2024

Disrupted mitochondrial response to nutrients is a presymptomatic event in the cortex of the APPSAA knock-in mouse model of Alzheimer disease

IntroductionReduced brain energy metabolism, mTOR dysregulation, and extracellular amyloid-{beta} oligomer (xcA{beta}O) buildup characterize AD; how they collectively promote neurodegeneration is poorly understood. We previously reported that xcA{beta}Os inhibit Nutrient-induced Mitochondrial Activity (NiMA) in cultured neurons. We now report NiMA disruption in vivo. MethodsBrain energy metabolism and oxygen consumption were recorded in APPSAA/+ mice using two-photon fluorescence lifetime imaging and multiparametric photoacoustic microscopy. ResultsNiMA is inhibited in APPSAA/+ mice before other defects are detected in these amyloid-{beta}-producing animals that do not overexpress APP or contain foreign DNA inserts into genomic DNA. GSK3{beta} signals through mTORC1 to regulate NiMA independently of mitochondrial biogenesis. Inhibition of GSK3{beta} with lithium or TWS119 stimulates NiMA in cultured human neurons, and mitochondrial activity and oxygen consumption in APPSAA mice. ConclusionNiMA disruption in vivo occurs before histopathological changes and cognitive decline in APPSAA mice, and may represent an early stage in human AD.

neuroscience↗

bioRxiv2024

SlWRKY80 recruits SlHDA1 to regulates the tomato fruit ripening and color transformation

Fruit ripening involves key transcription factors (TF). Despite the established importance of WRKY TFs in plant development, the involvement of WRKY and its underlying mechanism in the regulation of fruit ripening and color transformation remain unclear. Here, we discovered a phenomenon where SlWRKY80 is involved in the ripening and color transformation of tomato. Overexpression of SlWRKY80 shortened the color transition cycle of tomato fruit, whereas loss-of-function mutation in SlWRKY80 delays this process. On the 7th day after the color breakdown (Break+7), the fruit color was bright red in SlWRKY80-overexpression lines. SlWRKY80 could bind to downstream promoters of SlSGR1 and SlPSY1, thereby exerting a positive regulatory effect on the expression levels of SlSGR1 and SlPSY1. This regulatory activity led to the facilitation of chlorophyll a decomposition and carotenoid synthesis during the transition of fruit color, ultimately accelerating fruit ripening and color change. The SlWRKY80 knockout lines (slwrky80cr-3 and slwrky80cr-4) showed light red. Thr (The 69th amino acid) mutated to Ser of SlWRKY80 (slwrky80cr-46), SlHDA1 was recruited as a regulatory factor to enhance the regulation of downstream SlPSY1 by SlWRKY80, and inhibited the SlSGR1 expression by SlWRKY80 which maybe the reason why the slwrky80cr-46 knockout lines exhibited brown color. In conclusion, SlWRKY80 regulates the expression of SlSGR1 and SlPSY1 by recruiting SlHDA1, thereby regulating chlorophyll decomposition and carotenoid synthesis, and further participating in fruit maturation and related fruit color formation. This research has important guiding significance for breeding tomato germplasm with excellent commercial traits.

plant biology↗

bioRxiv2024

Characterization of RNA editing profiles in rice endosperm development

Rice (Oryza sativa L.) endosperm provides nutrients for seed germination and determines grain yield. RNA editing, a post-transcriptional modification essential for plant development, unfortunately, is not fully characterized during rice endosperm development. Here, we conduct genome re-sequencing and RNA sequencing for rice endosperms across five successive developmental stages and perform systematic analyses to characterize RNA editing profiles during rice endosperm development. We find that the majority of their editing sites are C-to-U CDS-recoding in mitochondria, leading to increased hydrophobic amino acids, and affecting structures and functions of mitochondrial proteins. Comparative analysis of RNA editing profiles across the five developmental stages reveals that CDS-recoding sites present higher editing frequencies with lower variabilities, and recoded amino acids, particularly caused by these sites with higher editing frequencies, tend to exhibit stronger evolutionary conservation across many land plants. Based on these results, we further classify mitochondrial genes into three groups that present distinct patterns in terms of editing frequency and variability of CDS-recoding sites. Besides, we identify a series of P- and PLS-class pentatricopeptide repeat (PPR) proteins with editing potential and construct PPR-RNA binding profiles, yielding candidate PPR editing factors related to rice endosperm development. Taken together, our findings provide valuable insights for deciphering fundamental mechanisms of rice endosperm development underlying RNA editing machinery. Author summaryRice endosperm development, a critical process determining quality and yield of our mankinds essential food, is regulated by RNA editing that provokes RNA base alterations by protein factors. However, our understanding of this regulation is incomplete. Hence, we systematically characterize RNA editing profiles during rice endosperm development. We find that editing sites resulting in amino acid changes, called "CDS-recoding", predominate in mitochondria, leading to increased hydrophobic amino acids and affecting structures and functions of proteins. Comparative analysis of RNA editing profiles during rice endosperm development reveals that CDS-recoding sites present higher editing frequencies with lower variabilities. Furthermore, evolutionary conservation of recoded amino acids caused by these CDS-recoding sites is positively correlated with editing frequency across many land plants. We classify mitochondrial genes into three groups that present distinct patterns in terms of editing frequency and variability of CDS-recoding sites, indicating different effects of these genes on rice endosperm development. In addition, we identify candidate protein factors associated closely with RNA editing regulation. To sum up, our findings provide valuable insights for fully understanding the role of RNA editing during rice endosperm development.

bioinformatics↗

bioRxiv2024

The lateral habenula integrates age and experience to promote social transitions in developing rats

Social behavior deficits are an early-emerging marker of psychopathology and are linked with early caregiving quality. However, the infant neural substrates linking early care to social development are poorly understood. Here, we focused on the infant lateral habenula (LHb), a highly-conserved brain region at the nexus between forebrain and monoaminergic circuits. Despite its consistent links to adult psychopathology, this brain region has been understudied in development when the brain is most vulnerable to environmental impacts. In a task combining social and threat cues, suppressing LHb principal neurons had opposing effects in infants versus juveniles, suggesting the LHb promotes a developmental switch in social approach behavior under threat. We observed that early caregiving adversity (ECA) disrupts typical growth curves of LHb baseline structure and function, including volume, firing patterns, neuromodulatory receptor expression, and functional connectivity with cortical regions. Further, we observed that suppressing cortical projections to the LHb rescued social approach deficits following ECA, identifying this microcircuit as a substrate for disrupted social behavior. Together, these results identify immediate biomarkers of ECA in the LHb and highlight this region as a site of early social processing and behavior control.

neuroscience↗