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Han, J.

Publications and source records attributed to Han, J..

At least 109 records · Page 6Linked to original sources
bioRxiv2025

Rescue of tomato yellow leaf curl virus mutants with heterologous iterons through in planta evolution

The single-stranded, circular DNA genomes of geminiviruses contain iterated motifs of 5-6 nucleotides, known as iterons, upstream of the replication protein (Rep) coding region. Iterons were previously found to interact with cognate Rep in a sequence-specific manner, and the iteron-Rep interaction was needed for viral DNA replication. Nonetheless, iterons of closely related viruses often have different sequences, suggesting diversifying selection. To identify selection pressures driving iteron diversification, we constructed tomato yellow leaf curl virus (TYLCV, isolate SH2) mutants in which the iteron motifs were replaced with those of closely related tobacco curly shoot virus (TbCSV, isolate Y35). All mutants replicated in inoculated leaves of Nicotiana benthamiana, but many failed to spread systemically. However, the systemic movement defects were mostly rescued by de novo mutations. Intriguingly, these de novo mutations did not restore the iterons to SH2 sequences. Rather, they likely enabled viral escape from repression exerted by the heterogenous Y35 iterons absent of a matching Rep. These results are consistent with iterons acting as sites of competitive binding by host-encoded transcription factors (TFs) and the cognate Rep. The iteron-TF binding commences as soon as viral genomes enter cell nuclei, committing genome copies to Rep mRNA transcription and protein translation; but also blocking them from replication. Conversely, iteron-Rep binding is possible only after Rep is produced, and likely repels TFs from some genome copies, permitting replication initiation. Testing this model through future research should clarify the intricate evolutionary interplays between geminiviruses and their crop hosts, and inform novel management strategies. Author SummaryGeminiviruses are important crop pathogens worldwide for which effective control measures are lacking, due to incomplete understanding of their evolutionary dynamics in infected plants. The current study focuses on a class of short sequence repeats in geminiviral genomic DNA, known as iterons, sitting immediately upstream of the viral gene encoding replication protein (Rep). Iterons are interesting because even though their positions and repeat patterns are conserved across all geminiviruses, their sequence identities are highly diverse. Our investigations revealed that contrary to previous reports, the sequence identity of iterons is non-essential for tomato yellow leaf curl virus (TYLCV) to replicate. Rather, they are repressors of replication, and this repression is overcome by their binding with cognate Rep. Our findings led to a new model postulating that the genome section encompassing iterons likely evolved specific sequence motifs to entice host-encoded transcription factors (TFs), facilitating rapid Rep production. Conversely, Rep promotes viral replication by removing TFs from genome copies through competitive iteron binding. Future testing of this new model will likely unveil novel targets for more effective management of crop diseases caused by geminiviruses.

evolutionary biology↗
bioRxiv2025

Modulating Hydrogel Stiffness Through Light-Based 3D Printing to Mimic Cardiac Fibrosis and Cardiomyocyte Dysfunction Using hiPSC-Derived Cells

The human hearts limited regenerative capacity is a significant barrier to addressing cardiovascular disease (CVD). This is particularly true for cardiac fibrosis, a form of CVD wherein the wound healing process has gone awry. In cardiac fibrosis, excessive scar tissue formation due to dysregulated remodeling of the hearts extracellular matrix (ECM) results in increased stiffness that reduces cardiac output and can lead to heart failure. This dysregulated ECM deposition is driven by activated cardiac fibroblasts, where cell substrate stiffness is known to play a role in cardiac fibroblast activation. New preclinical models that accurately recapitulate the behavior of activated cardiac fibroblasts are needed to better understand and treat cardiac fibrosis. To this end, we describe a model wherein human induced pluripotent stem cell (hiPSC)-derived cardiac fibroblasts (HCFs) are cultured on 3D printed hydrogels of tunable stiffness, fabricated using dosage controlled digital light processing (DLP). We demonstrate that our model can induce HCF activation in the absence of TGF{beta}, a key mediator of fibroblast activation, surpassing the activation levels seen with HCFs activated with TGF{beta} on protein-coated tissue culture plates. Furthermore, combining stiffer hydrogels with TGF{beta} recapitulates fibroblast activation similar to what is observed in native cardiac tissue. Lastly, by indirectly coculturing HCFs seeded and activated on these stiff hydrogels with hiPSC-derived cardiomyocytes, we demonstrate that the activated HCFs in our cardiac fibrosis model can impair cardiomyocyte function, mimicking the deleterious effects of cardiac fibrosis.

bioengineering↗
bioRxiv2025

Lysosomal control of proteostasis and reproductive capacity by conserved LMD-3 protein in C. elegans

The reproductive capacity declines markedly with female age in humans. Similarly, C. elegans exhibit a rapid age-dependent decline in fecundity shortly after reaching adulthood. Emerging evidence suggests a significant link between proteostasis disruption and reduced fertility in both worms and humans, but the regulatory mechanisms governing this connection are not fully understood. Here, we report that LMD-3, a LysM domain protein, regulates proteostasis and reproductive capacity in C. elegans. The deficiency of lmd-3 leads to striking defects in oxidation resistance and constitutively high cellular stress responses, such as ER stress response and cytosolic stress response. We demonstrate that lysosome-localized LMD-3 protein interacts with vitellogenin and V-type ATPase, which drives proton-transporting and lysosomal lumen acidification. LMD-3 regulation of lysosomal function is essential for maintaining yolk protein homeostasis and reproductive health. We also identify that vitamin B12 (meCbl) supplementation revert the fecundity decline of lmd-3 mutants by reducing oxidative stress and improving lysosomal function. Together, these findings emphasize the role of LMD-3 in sustaining protein homeostasis and oocyte quality control, and establish a model system to find potent therapeutic strategies to increase reproductive health.

cell biology↗
bioRxiv2025

An in vivo rat lumbar spine instability model induced by intervertebral disc injury

Intervertebral disc (IVD) degeneration is a potential contributor to low-back pain. While experimental IVD injury models have demonstrated IVD structural changes, the early mechanical consequences remain unclear. This study aimed to establish a rat model of lumbar spine instability via IVD injury and assess back musculature adaptations to IVD injury. Thirty-one adult male Wistar rats were assigned to three groups: IVD knife stab lesion (knife), IVD needle puncture (needle), and sham surgery control (control). In the knife and needle groups, L4/L5 IVDs were injured at 14 weeks of age. One-two weeks post-intervention, lumbar multifidus (MF) and medial longissimus (ML) muscles were excised, L4-L5 spinal segments were harvested for mechanical testing, and IVDs were collected for histology. The needle group exhibited lower peak stiffness, peak moment, and hysteresis than controls in flexion, with no difference in lateral bending. IVD height and area did not differ between groups, but the needle group had a smaller nucleus relative to annulus area compared to controls. Morphological changes were observed in both injury groups. The needle group showed higher normalized ML mass, while normalized MF mass was unchanged. In conclusion, a rat model of lumbar spine instability was successfully established via IVD needle injury.

bioengineering↗
bioRxiv2025

Characterization of the glycoproteins of novel fish influenza B-like viruses

Novel influenza-like virus sequences previously identified in fish and amphibians were found to cluster as a sister clade of influenza B viruses, but have thus far remained uncharacterized. We demonstrate that salamander influenza-like virus (SILV) HA is functionally divergent from influenza B virus HA and does not bind to 2,3- and 2,6-linked sialic acids. However, the HAs of Siamese algae-eater influenza-like virus (SAEILV) and chum salmon influenza-like virus (CSILV) bind to 2,3 linked sialic acid. Furthermore, SAEILV HA binds to sialyated Lewis X, is activated by human airway enzymes and is fusogenic at a wide range of pH conditions. SAEILV NA has a highly conserved active site and a similar structure to other known NAs. We also determined the cryo-electron microscopy structure of the HA of a previously described virus from the same sister clade, the Wuhan spiny eel influenza virus (WSEIV). Importantly, no cross-reactive antibodies against these HAs or NAs were found in the human serum, suggesting that humans are immunologically naive to these viruses. One sentence summaryNovel influenza like-viruses, displayed different target receptor specificity and limited antigenic conservation of the HA and NA relative to influenza B Viruses.

microbiology↗
bioRxiv2025

Persistently increased expression of PKMzeta and unbiased gene expression profiles identify hippocampal molecular traces of a long-term active place avoidance memory and 'shadow' proteins

Long-term memory formation transiently activates Ca2+-calmodulin kinase II and atypical protein kinase C isoform iota/lambda, whereas persistent activation of the other atypical PKC, protein kinase M zeta (PKM{zeta}), together with its interacting partner, the scaffolding-protein KIBRA (Wwc1), are necessary for maintaining potentiated synapses and memory. Here, we use immediate-early gene (IEG) Arc activation during active place avoidance memory expression to tag memory-activated neurons with EYFP-ChR2. PKM{zeta} immunohistochemistry identified which hippocampal synaptic pathways are persistently altered. EYFP-PKM{zeta} colocalization persistently increases in the hippocampal trisynaptic pathway (dentate gyrus [DG][->]CA3[->]CA1) tracing a one-month-old PKM{zeta} engram. DG, CA3, and CA1 transcriptional profiling identifies that memory persistence correlates with upregulated immediate-early-genes Arc, Fos, and NPas4 in DG, but not with PKM{zeta} or most genes known to be crucial for LTP and memory. This rules out strong memory-related transcriptional regulation, but not regulation of mRNA translation or altered stability of "shadow proteins" like PKM{zeta} that, despite being crucial for memory maintenance, evade detection by unbiased transcriptome profiling. In contrast, our method Correlation Signal Co-cluster Reduction (C-SCoRe) incorporates weak linear and non-linear gene correlations and highlights network interaction changes predicting memory, and related IEG and Prkcz/Wwc1 expression. Manifold transcriptional relationships can reveal shadow molecular components of long-term memory.

neuroscience↗
bioRxiv2025

Dimethyl fumarate reprograms cervical cancer cells to enhance antitumor immunity by activating mtDNA-cGAS-STING pathway

BackgroundCervical cancer (CC) remains a significant global health challenge for women, especially in advanced stages where effective treatments are limited. Current immunotherapies, including PD-1/PD-L1 blockades and adoptive T cell therapies, show limited response rates and durability. Dimethyl fumarate (DMF), an FDA-approved drug for autoimmune diseases, has demonstrated that it might exhibit direct antitumor activity in several cancers. However, its influence on anti-tumor immunity and its function in CC remain poorly understood. This study aims to investigate the therapeutic potential of DMF in CC models and elucidate its underlying mechanisms of action. MethodsCC cell lines and mouse models were treated with DMF. Transcriptional level changes in cervical cancer cells following DMF treatment were analyzed by RNA-seq. Mitochondrial DNA (mtDNA) release, and cGAS-STING activation were assessed via qPCR, immunofluorescence, immunoblotting and ELISA. CD8+ T cell recruitment was analyzed by flow cytometry. Combinatorial therapies (DMF + anti-PD-1/TILs) were tested in syngeneic or patient-derived xenografts (PDX) models. ResultsDMF treatment induces mitochondrial dysfunction in tumor cells, resulting in the release of mtDNA into the cytosol. The cytosolic mtDNA activates the cGAS-STING-TBK1 pathway and type I interferon response, leading to the secretion of CCL5 and CXCL10, thereby enhancing CD8 T cell infiltration. Additionally, DMF exhibits synergistic effect with PD-1 blockade in murine CC model, and can enhance the therapeutic efficacy of adoptively transferred T cells toward CC patient-derived xenografts model. ConclusionThis work elucidated that DMF reprograms CC cells to activate the mtDNA-cGAS-STING pathway, fostering a chemokine-rich microenvironment that recruits CD8+ T cells. Its synergy with PD-1 blockade or TIL therapy underscores its potential as an immunomodulatory adjuvant. These findings suggest that DMF holds promise as a novel immunotherapeutic strategy for improving clinical outcomes in CC.

immunology↗
bioRxiv2025

Exploration of Novel Biomarkers through a Precision Medicine Approach Using Multi-omics and Brain Organoids in Patients with Atypical Depression and Psychotic Symptoms

Major depressive disorder (MDD) with atypical features accompanied by psychotic symptoms represents a severe and under-researched subtype of depression and severe mental illness, characterized by significant personal and social impact. This study aims to explore novel biomarkers through a precision medicine approach by integrating clinical data, white blood cell (WBC) single-cell RNA sequencing (scRNA-seq), plasma proteomics, and brain organoid models to uncover immunological and neurological alterations in patients with this condition. Patients exhibited elevated stress, anxiety, and depression levels, with increased WBC counts. Plasma proteomic profiling identified an upregulation of proteins implicated in synaptic formation, including Doublecortin-Like Kinase 3 (DCLK3) and Calcyon (CALY), as well as immune-related proteins such as Complement Component 5 (C5). WBC scRNA-seq revealed significant neutrophil and monocyte transcriptomic alterations, suggesting increased inflammation and immune dysregulation. Patient-derived brain organoids display reduced growth and distinct gene expression patterns compared to controls, particularly under dexamethasone-induced stress conditions. Integrating multi-omics data and brain organoid models offers a novel framework for understanding the pathophysiology of psychiatric disorder, which is one of the most complex disorders.

neuroscience↗
bioRxiv2025

Breaking the Link: Neural Dissociation of Attention and Working Memory through Inhibitory Control

Attention and working memory (WM) encoding have traditionally been considered inseparable processes with shared neural mechanisms. Here, using an innovative experimental design and a multimodal approach, we provide the first direct neural evidence that attention and WM encoding are dissociable. Functional MRI identifies the supramarginal gyrus (SMG) as the key region enabling this dissociation, while dynamic causal modeling reveals the neural circuitry through which the SMG exerts inhibitory control over attentional representations, regulating their integration into WM. Furthermore, neuromodulation via transcranial direct current stimulation (tDCS) demonstrates that enhancing SMG activity strengthens this inhibitory control, providing causal evidence for the dissociation mechanism. A second tDCS experiment with varied stimuli confirms the generalizability of this mechanism and reinforces the robustness of our results. These findings challenge the long-standing view that attention and WM encoding form a continuous process, demonstrating instead that they constitute two dissociable neural processes of information selection.

neuroscience↗
bioRxiv2025

Molecular insights into early malignant transition of hepatocellular carcinoma

The molecular continuum of premalignant-to-malignant transition remains elusive in carcinogenesis, primarily due to the difficulty in sampling transitional lesions. Here, we present comprehensive genomic and immunological profiling of 21 very early hepatocellular carcinomas (veHCCs) arising within 17 cancer-prone DNs. Surprisingly, 82% of cancer-prone DNs harbored TERT alterations, suggesting a predisposing rather than causative role in malignancy transition. A substantial increase in CNA burden, rather than SNV, was noted, indicating a role of chromosome instability in malignancy transition. Additionally, veHCC-originating DNs showed immune inactivity, not falling into the prevailing paradigm that HCCs develop in a context of chronic inflammation. 43% of veHCCs showed an inflamed phenotype with relatively mild CNA burden but already exhibited immune evasion features. Two major evolutionary scenarios were thus proposed: 1) CNA-dominant progression and 2) early immune evasion of those with mild CNA burden. Collectively, our findings illustrate previously unexplored molecular paradigms in HCC initiation, highlighting the therapeutic potential of immunotherapy for early intervention.

cancer biology↗
bioRxiv2025

Matrix Stiffness Regulates Mechanotransduction and Vascular Network Formation of hiPSC-Derived Endothelial Progenitors Encapsulated in 3D Hydrogels

The mechanical properties of the extracellular matrix (ECM), particularly stiffness, regulate endothelial progenitor responses during vascular development, yet their behavior in physiologically compliant matrices (<1 kPa) remains underexplored. Using norbornene-modified hyaluronic acid (NorHA) hydrogels with tunable stiffness (190-884 Pa), we investigated how hydrogel stiffness influences cell morphology, endothelial maturation, mechanotransduction, and microvascular network formation in human induced pluripotent stem cell-derived endothelial progenitors (hiPSC-EPs). Our findings reveal a stiffness-dependent tradeoff between mechanotransduction and vascular network formation. At intermediate stiffness (551 Pa), cells exhibited the greatest increase in endothelial marker CD31 expression and Yes-associated protein (YAP)/ transcriptional coactivator with PDZ-binding motif (TAZ) nuclear translocation, indicating enhanced mechanotransduction and endothelial maturation. However, this did not translate to superior plexus formation. Instead, the most compliant matrix (190 Pa) supported greater vascular connectivity, characterized by longer branches ([~]0.03/volume vs. 0.015 at 551 Pa) and enhanced actin remodeling. 3D cell contraction measurements revealed a 15.6-fold higher basal displacement in compliant hydrogels, suggesting that cell-generated forces and matrix deformability collectively drive vascular morphogenesis. Unlike prior studies focusing on pathological stiffness ranges (>10 kPa), our results emphasize that vascularization is not solely driven by the most mechanotransductive environment but rather by a balance of compliance, contractility, and cell-induced remodeling. These findings underscore the need to design hydrogels that provide sufficient mechanotransduction for endothelial maturation while maintaining compliance to support dynamic vascular morphogenesis. This work provides a mechanically tuned framework for optimizing microenvironments to balance endothelial differentiation and vascular network formation in tissue engineering and regenerative medicine.

bioengineering↗
bioRxiv2025

Analysis of Nematode Ventral Nerve Cords Suggests Multiple Instances of Evolutionary Addition and Loss of Neurons

Despite their diversity in habitats, nematodes are often considered to have a highly conserved neuroanatomy. This premise is based on only a subset of the nematode phylogenetic tree focused on the more diverged clades within the class Chromadorea, which includes the model organism Caenorhabditis elegans, thereby limiting our understanding of macroevolutionary trends in nervous system structure. To approach this problem, we used nuclear morphology to quantify the number of neurons in the nematode ventral nerve cord (VNC) to identify evolutionary patterns in neuroanatomical organization within the basal clades of Chromadorea and Enoplea. DAPI staining revealed significant VNC neuron count variations among families, with notable differences between the classes Enoplea and Chromadorea and among Enoplean species. These results may indicate a degree of evolutionary morphological stasis in later diverging Chromadorean clades. To further examine developmental patterns and potential variation in Enoplean nervous system architecture, we established an isogenic culture of the nematode Mononchus aquaticus. We found that while M. aquaticus contained four times as many VNC neuronal nuclei as C. elegans, the VNC had a similar developmental timeline during post-embryonic stages. However, dye-filling assays revealed an extensive distribution of neurons along the lateral body wall, which have no obvious homolog to C. elegans. We found that M. aquaticus is capable of sustained movement following bisection that may imply a more distributed nervous system network. Our results provide a roadmap for understanding phylum-wide nervous system evolution and demonstrate large-scale differences between Enoplean and Chromodorean nervous systems.

evolutionary biology↗
bioRxiv2025

Functional, Immunogenetic, and Structural Convergence in Influenza Immunity between Humans and Macaques

Human B cell immunity to the influenza hemagglutinin (HA) stem region, a universal influenza vaccine target, is often stereotyped and immunogenetically restricted, posing challenges for study outside humans. Here, we show that macaques vaccinated with a HA stem immunogen elicit human-like public B cell lineages targeting two major conserved sites of vulnerability, the central stem and anchor epitopes. Central stem antibodies were predominantly derived from VH1-138, the macaque homolog of human VH1-69, a VH-gene preferentially used in human central stem broadly neutralizing antibodies (bnAbs). Similarly, macaques produced anchor bnAbs with the human-like NWP motif. Both bnAb lineages were functionally and structurally analogous to their human counterparts, with recognition mediated largely by germline-encoded motifs. Thus the macaque immunoglobulin repertoire supports human-like public bnAb responses to influenza HA. Moreover, this underscores the utility of homologous germline-encoded immunity, suggesting that immune repertoires of macaques and humans may have been similarly shaped during evolution. HIGHLIGHTS[bullet] Functional human-like public antibody lineages can be elicited to HA stem supersites in macaques. [bullet]Macaque central stem bnAbs are predominantly derived from VH1-138, a VH-gene homologous to human VH1-69. [bullet]The human-like CDR L3 NWP anchor epitope-targeting lineage can be elicited in macaques. [bullet]Central stem and anchor bnAbs from humans and macaques engage their respective epitopes with atomic level similarity.

immunology↗
bioRxiv2025

Human monoclonal antibodies that target clade 2.3.4.4b H5N1 hemagglutinin

The highly pathogenic avian influenza H5N1 virus clade 2.3.4.4b has been spreading globally since 2022, causing mortality and morbidity in domestic and wild birds and mammals, including infection in humans, raising concerns about its pandemic potential. We aimed to generate a panel of anti-hemagglutinin (HA) human monoclonal antibodies (mAbs) against the H5 protein of clade 2.3.4.4b. H2L2 Harbour Mice(R), which express human immunoglobulin germline genes, were immunized with H5 and N1 recombinant proteins from A/mallard/New York/22-008760-007-original/2022 H5N1 virus, enabling the generation of human chimeric antibodies. Through hybridoma technology, sixteen full human mAbs were generated, most of which showed cross-reactivity against H5 proteins from different virus variants. The functionality of the sixteen mAbs was assessed in vitro using hemagglutination inhibition and microneutralization assays with viruses containing a clade 2.3.4.4b HA. Fourteen out of the sixteen mAbs neutralized the virus in vitro. The mAbs with the strongest hemagglutination inhibition activity also demonstrated greater neutralizing capacity and showed increased protective effects in vivo when administered prophylactically or therapeutically in a murine H5N1 challenge model. Using cryo-electron microscopy, we identified a cross-clonotype conserved motif that bound a hydrophobic groove on the head domain of H5 HA. Akin to mAbs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the coronavirus 2019 (COVID-19) pandemic, these mAbs could serve as important treatments in case of a widespread H5N1 epidemic or pandemic.

microbiology↗
bioRxiv2025

Action features dominate cortical representation during natural vision

Cortical resources are allocated into systems specialized for processing ecologically relevant features of the world. These features are typically studied in isolation using controlled experimental stimuli, making it difficult to assess the relative importance of different kinds of features that tend to overlap during natural vision. In the current study, we evaluated the relative contributions of action, agent, and scene features in predicting cortical activity while participants viewed a 1-hour nature documentary. We tested four sets of model features: semantic vectors capturing the observed action, agent, and scene features derived from an annotation of the stimulus, as well as low-level visual motion-energy features. We used banded ridge regression to fit vertex-wise encoding models from the combination of all four sets of features. While each set of features predicted neural activity in the expected areas, the action features predicted more widespread activity. A variance partitioning analysis revealed that the action features captured the most unique variance in neural activity across ten times as many cortical vertices as the agent or scene features. Our findings suggest that cortical activity during dynamic, natural vision is dominated by features for understanding the actions of others.

neuroscience↗
bioRxiv2025

Development of a High-throughput Morphological Assay for Evaluating Mesenchymal Stromal Cell-derived Extracellular Vesicle Modulation of Brain Pericyte Secretory Phenotype

Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are a promising therapeutic tool for treating many neurodegenerative diseases. Neuroinflammation plays a major role in many of these conditions through an orchestration of interdependent processes that lead to the breakdown of the blood-brain barrier (BBB), infiltration of immune cells and neuronal death. MSC-EVs have shown preliminary evidence of modulating neuroinflammation, but their mechanisms of action are still unknown. Therefore, we explored the potential of MSC-EVs in modulating brain pericytes, a cell type that plays a critical role in BBB maintenance but has not been investigated as a therapeutic target for MSC-EVs. Brain pericytes are multifaceted cells that can modulate neuroinflammation through their involvement in BBB homeostasis, as well as the innate and adaptive immune response. Pericyte morphology has been shown to change in response to inflammatory stimuli in vivo, hence, we used this behavior to develop a quantitative morphological profiling approach to assess the immunomodulatory function of MSC-EVs in a high-throughput, low-cost manner. Using this assay, we were able to demonstrate that MSC-EVs manufactured under various conditions (2D, 3D, and in response to cytokine priming) could induce distinct pericyte morphological responses indicative of changes in secretion of chemokines and cytokines relevant to neuroinflammation.

bioengineering↗
bioRxiv2025

Stress-activated neuronal ensemble in the supramammillary nucleus stores anxiety but not memory

Anxiety is a prevalent negative emotional state induced by stress; however, the neural mechanism underlying anxiety is still largely unknown. We used acute and chronic stress to induce anxiety and test anxiety-like behavior; immunostaining, multichannel extracellular electrophysiological recording and Ca2+ imaging to evaluate neuronal activity; and virus-based neuronal tracing to label circuits and manipulate circuitry activity. Here, we identified a hypothalamic region, the supramammillary nucleus (SuM), plays important role in anxiety-like behavior. We then characterized a small ensemble of stress-activated neurons (SANs) that are recruited by stress. These SANs respond specifically to stress, and their activation robustly increases anxiety-like behavior in male mice. We also found that ventral subiculum (vSub)-SuM projection but not dorsal subiculum (dSub)-SuM projections encode anxiety-like behavior and that inhibition of these vSub-SuM projections has an antianxiety effect. These results indicate that the reactivation of stress-activated supramammillary cells and relevant neural circuits are important neural processes underlying anxiety-like behavior.

neuroscience↗