Biology subjects

Park, G.

Publications and source records attributed to Park, G..

At least 19 recordsLinked to original sources

bioRxiv2026

Netrin signaling shapes sexually dimorphic neurite branching of a sex-shared interneuron in C. elegans

Sexually dimorphic behaviors arise from underlying differences in neural circuit architecture between the sexes, yet the molecular mechanisms that establish these structural differences remain poorly understood. In Caenorhabditis elegans, the sex-shared interneuron AVG exhibits sexually dimorphic synaptic connectivity, offering a model for investigating the development of sexually dimorphic neuronal morphology. Here, we identified that AVG displays male-specific neurite branching and demonstrated that the conserved axon guidance cue UNC-6/Netrin and its receptor UNC-40/DCC are essential for this structural remodeling. Cell-specific manipulation of sexual identity revealed that male identity confers branching competence to AVG. Loss of UNC-6 or UNC-40 abolished branch formation, whereas loss of the alternate Netrin receptor UNC-5/Unc5 had no detectable effect. Cell-specific rescue experiments showed that UNC-40 functions in AVG through its UNC-6 binding domains. Furthermore, genetic ablation of the male-specific presynaptic neuron PCA, which expresses unc-6, diminished AVG branch length, establishing PCA as a candidate local source of UNC-6. Together, our findings support a model in which presynaptic UNC-6/Netrin cues from male-specific neurons promote dimorphic neurite branching in sex-shared neurons, illustrating how evolutionarily conserved signaling molecules are redeployed during sexual maturation to sculpt sex-specific neural circuits.

neuroscience↗

bioRxiv2026

Host type governs influenza evolutionary strategy across reservoir and spillover hosts

Despite its high propensity for host switching, the evolutionary mechanisms underlying influenza host adaptation remain unclear. H3Nx influenza viruses are uniquely generalist, with long-term lineages that circulate in avian, human, swine, equine, and canine hosts. Using 13,295 H3Nx sequences, we quantified host-specific adaptive evolution and developed a pipeline to map reassortment events onto trees with measures of statistical uncertainty. We find that while H3Nx viruses in mammals undergo adaptive evolution in HA and NA, viruses in birds experience very little directional selection. Instead, avian lineages exhibit high rates of reassortment, frequently generating novel reassortant lineages that persist transiently and turn over rapidly. 29.8-47.4% of all avian reassortant lineages are purged within the first year of circulation, and reassortment shows no fitness benefit in birds. In contrast, reassorted lineages in swine are more likely to persist long-term, suggesting that reassortment in swine may be broadly beneficial. Segment-specific reassortment patterns were also distinct between avian and mammalian viruses, with NA reassorting more frequently than expected in birds, but less frequently than expected in swine. Reassortment events are enriched between mammalian, but not avian, host switches, suggesting that reassortment may be most beneficial for mediating host switches among mammalian species. Together, our data suggest that host differences drive fundamentally different evolutionary outcomes for influenza viruses, transitioning from reassortment-dominant evolution in their avian reservoir, to varying degrees of adaptation upon establishment in mammals.

evolutionary biology↗

bioRxiv2026

Predator type shapes call-type composition and post-threat vocal dynamics in Japanese quail (Coturnix japonica): a pilot case-series

Japanese quail (Coturnix japonica) rely on an extensive vocal repertoire to coordinate social behaviour and respond to predation risk, yet how individual call types are modulated by predator identity remains poorly characterized. In this pilot case-series, two sexually mature Japanese quail (each contributing more than 2,000 classified vocalizations across repeated predator-exposure trials) were exposed to simulated aerial (hawk) and terrestrial (cat) predator stimuli across four social contexts, before, during, and after stimulus presentation. Vocalizations were classified, via blind dual-observer review, into 18 spectrographically distinct call types (an exploratory repertoire estimate, not independently statistically validated), of which 10 were acoustically characterized. Chi-square analyses of the full call-type composition revealed highly significant differences between hawk and cat exposure in both individuals (both p < 0.0001); call types 5 and 10 were significantly cat-biased and call type 2 was significantly hawk-biased in both individuals. An exploratory correlation suggested that call types with a higher maximum frequency tended to be relatively hawk-biased (Spearman rho = -0.67, p = 0.033, uncorrected for multiple comparisons). Independently, call-type composition shifted significantly between the pre- and post-exposure phases in all four individual-by-predator combinations (all p < 0.0001), driven substantially by a consistent post-exposure increase in call type 9 across both individuals and both predator classes. Additional exploratory analyses of social-context (mirror and concealed-conspecific) effects on call-type composition are presented in the supporting information. Given the small sample size (n = 2), these findings are presented as case-based, hypothesis-generating observations intended to justify and inform a fully powered follow-up study, rather than as population-level conclusions.

animal behavior and cognition↗

bioRxiv2026

The ENIGMA-PD-WML Pipeline: A Containerized, User-Friendly Approach for Accurate, Standardized Segmentation of White Matter Lesions in Multi-Site MRI Data

Understanding vascular contributions to disease is a major unmet need. White matter lesions (WML) are an accepted imaging marker of cerebral small vessel disease, giving insights into its related pathologies. A unified approach for WML analyses in large multi-site data is lacking despite the need for pooling of data to overcome the limitations of often small heterogenous MRI studies which make subtyping and identifying patterns within disease groups difficult. Our ENIGMA-PD-WML pipeline is an open-source containerized pipeline containing all the code and packages required for pre-processing, processing and post-processing of T1-weighted and FLAIR data, outputting accurate and reproducible binary WML maps using a UNet approach. The pipeline provides a standardized image analysis approach for WML and outputs data in both native and MNI space to allow for sharing and pooling of data from multiple sites for large-data analysis. In addition to a reliable standardized approach for WML segmentation, key priorities when developing the pipeline included: usability, i.e., requiring minimal manual input and technical expertise to use, and suitability to run on various MRI scanners and acquisition parameters as is common in multi-site data. This paper describes the pipeline in detail, with rationale for each step, providing transparency and facilitating its usage to overcome reproducibility issues in large-scale WML analyses.

neuroscience↗

bioRxiv2026

Sex Effect of E-liquid Constituents on Atherosclerosis and Gut Dysbiosis in ApoE-/- Mice

RationaleThe role of sex in the effects of vaping and individual aerosolized e-liquid constituents on atherosclerosis, vascular aging, and gut microbiome remodeling remains poorly characterized. ObjectiveTo determine the contribution of e-cigarette aerosol components to vascular senescence, atherosclerosis, and gut microbiome dysbiosis in ApoE-/- mice and vascular smooth muscle cell (VSMC) viability and senescence. MethodsMale and female ApoE-/- mice were exposed to e-liquid constituents (vehicle, vehicle plus nicotine, and vehicle plus nicotine plus menthol) for 48 minutes per day, 5 days per week for 16 weeks, with vascular pathology assessed in vivo. VSMCs isolated from aortas of wild-type and ApoE-/- male and female mice were exposed to aerosolized e-liquids and evaluated for cellular senescence. ResultsExposure to all tested e-liquid formulations, including vehicle, nicotine-containing, and menthol-containing aerosols, increased atherosclerosis in both male and female mice, with the most robust effects observed in the nicotine-containing formulation and in the descending aorta. Females exhibited greater sensitivity to e-liquid exposure, with increased plaque accumulation in both the aortic arch and descending aorta, while the addition of menthol was associated with reduced plaque burden compared with nicotine alone in both sexes. Novel findings show that e-liquid exposure also altered gut microbial composition in a sex- and exposure-dependent manner, with nicotine causing the greatest dysbiosis and menthol exerting modulatory, but not restorative, effects. Notably, Alloprevotella emerged as a key discriminating genus associated with reduced plaque burden, supporting a potential link between gut microbial remodeling, inflammatory regulation, and atherosclerosis. ConclusionsThese findings demonstrate that individual e-liquid aerosol components increase atherosclerosis and alter the gut microbiome in a sex-specific manner, with nicotine producing the most pronounced pro-atherogenic effects and the addition of menthol reducing these effects, without eliminating overall atherosclerotic risk.

physiology↗

bioRxiv2026

Deep Plasma Proteomics Coupled with Functional Genomics Reveals Drivers of Parkinson's Disease Progression and Levodopa Response

Parkinsons disease (PD) is a progressive neurodegenerative disorder lacking disease-modifying therapies, and its clinical management is limited by the absence of accessible biomarkers for tracking disease progression and treatment response. To map these complex disease trajectories, we implemented an ultra-deep plasma proteomics workflow integrating Mag-Net extracellular vesicle enrichment with Orbitrap Astral mass spectrometry to profile longitudinal samples from PD patients. This approach quantified 6,481 plasma proteins at unprecedented depth in PD studies, revealing distinct signatures directly associated with disease duration and dopaminergic therapy exposure. Candidate biomarkers were subsequently validated in an independent cohort using ELISA, demonstrating robust predictive utility in AI-driven prediction models. To uncover the mechanistic drivers underlying these systemic changes, we intersected our proteomic data with novel proteome-wide gene overexpression perturbation screens designed to identify regulators of alpha-synuclein pre-formed fibril (PFF) uptake and PFF-induced neuronal toxicity. Finally, an integrative network analysis combining three independent proteome-wide assays revealed that key pathological hubs, such as CD14, IFNG, and PLAT, are targets of currently approved pharmacological agents. Collectively, these findings provide a comprehensive, systems-level map for PD biomarker discovery and highlight druggable pathways to advance precision medicine strategies.

neuroscience↗

bioRxiv2026

PersonaAI: An Interactive Agentic-AI Framework for Autonomous Hypothesis Generation and Validation in Aging

Elucidating the mechanisms of aging is impeded by its stochastic, multi-scale nature and cellular heterogeneity, challenges that are compounded by the overwhelming volume of biomedical literature and the complexity of genome-wide datasets. To overcome these barriers, we present PersonaAI, an interactive agentic-AI framework that acts as a digital co-scientist. By integrating literature-based reasoning with autonomous in silico validation, PersonaAI synthesizes over 560,000 aging-related publications via retrieval-augmented generation (RAG) to propose mechanistic hypotheses. These hypotheses are subsequently validated by autonomous agents utilizing single-cell RNA-seq data. Using a temporal cutoff strategy restricted to pre-2020 literature, we demonstrate that PersonaAI can generate hypotheses effectively validated by post-2021 discoveries, proving its capacity for inference beyond simple information retrieval. In application, the system identified senescent Cirbp+ hepatocytes as a liver-intrinsic aging program and uncovered a middle-aged, male-specific decline in adipose stem and progenitor cells, driven by vascular niche deterioration and disrupted VEGF-VEGFR signaling. These results establish PersonaAI as a scalable platform that augments human intuition with autonomous data-driven validation, providing a generalizable platform for accelerating discovery in aging biology.

bioinformatics↗

bioRxiv2025

CD74 regulates antitumor immunity in melanoma by reprogramming dendritic cell immunogenicity and migration

Metastatic cutaneous melanoma remains a major therapeutic challenge, as many patients fail to respond or relapse following immune checkpoint therapy. The function of CD74, originally described as an MHC-II chaperone and receptor for macrophage migration inhibitory factor, remains poorly understood in tumor immunity. In this study, we show that systemic CD74 deletion in a syngeneic melanoma model significantly delayed tumor growth and reshaped the tumor immune microenvironment, and synergized with immune checkpoint blockade. Tumors in Cd74-/- mice had more effector and memory CD8+ T cells producing IFN-{gamma} and granzyme B than in control mice. Loss of CD74 promoted expansion of migratory cDC1s with elevated MHC-I and CCR7 expression. Cd74-/- professional antigen presenting cells increased cross-priming capacity for tumor-derived antigens in vivo and in vitro. Absence of CD74 induced the expression of CCR7, a key lymph node homing molecule, on cDCs and enhanced their ability to migrate towards the CCL19 ligand in single cell tracking analyses. These findings identify CD74 as a regulator of dendritic cell function and a promising therapeutic target to improve melanoma immunogenicity. One Sentence SummaryCD74 restrains cross-priming and migration capacity of dendritic cells, leading to impaired CD8+ T-cell infiltration and activation in tumor immunity.

immunology↗

bioRxiv2025

Determination of α-Synuclein Protein Interactions by μMap Photo-proximity Labeling

Fibrillar aggregates of the natively disordered protein -synuclein (S) are hallmarks of Parkinsons disease and related neurodegenerative disorders termed synucleinopathies. Here, we used micromap ({micro}Map) photo-proximity labeling to determine the interactomes of S monomers and fibrils in mouse brain lysate to better understand both the loss of healthy function and gain of toxic function aspects of synucleinopathies. Several S variants were synthesized and characterized, showing that the small size (1 kDa) of the Ir catalyst attached through a Cys-maleimide linkage makes it minimally-perturbing to S, with a narrow labeling radius that allows one to identify interactome differences between different regions of S. Monomer and fibril interactomes were compared to each other and to previous proximity labeling data sets for validation and several examples of further investigations are demonstrated, including Western blotting, super-resolution microscopy, and {micro}Map in primary neurons.

biochemistry↗

bioRxiv2025

Cinnamomum cassia Extract and Its Novel Isolated Compound Suppress Inflammation via Autophagy Induction in Sepsis

Uncontrolled inflammation is central to the development of diseases such as sepsis, and autophagy has emerged as a critical regulatory mechanism in this process. The ethanol extract of Cinnamomum cassia (EECC) was identified as a potent autophagy inducer through high-throughput LC3 reporter screening. EECC enhanced autophagic flux, as confirmed by RFP-GFP-LC3 imaging and immunoblotting. It also suppressed Toll-like receptor signaling and reduced pro-inflammatory cytokine production in macrophages. EECC inhibited nuclear factor-{kappa}B signaling in an autophagy-dependent manner, as this effect was reversed by autophagy inhibitors. To identify active constituents, 24 compounds were isolated from EECC, including six novel structures. Among the novel compounds, Cassitamine F exhibited dual activity as an autophagy inducer and inflammation suppressor. In a lipopolysaccharide-induced sepsis model, Cassitamine F significantly reduced serum levels of pro-inflammatory cytokines. These findings suggest that EECC and Cassitamine F may hold therapeutic potential for autophagy-targeted treatment of sepsis and other inflammation-related disorders. Highlights- Ethanol extract of Cinnamomum cassia (EECC) identified as a potent autophagy inducer via high-throughput LC3 HiBiT screening. - EECC suppresses Toll-like receptor signaling and pro-inflammatory cytokines through autophagy-dependent pathways. - Twenty-four compounds were isolated from EECC, including six novel structures (Cassitamine A-F). - Cassitamine F exhibits dual activity: induction of autophagy and inhibition of inflammation. - Cassitamine F significantly reduces serum cytokine levels in an LPS-induced sepsis model, suggesting therapeutic potential.

pharmacology and toxicology↗

bioRxiv2025

Transcription factors overcome the repressive impact of Polycomb-associated methylation in tumors

DNA methylation is a key epigenetic regulator often disrupted in cancer, yet how promoter methylation dynamics translate into transcriptional changes during cancer progression remains incompletely understood. Here, we employed targeted bisulfite sequencing and RNA-seq on paired tumor and non-tumor tissues from 80 Korean colorectal cancer (CRC) patients to map promoter methylation and gene expression dynamics. Promoters with high baseline methylation in non-tumor tissues tended to become hypomethylated in tumors, while those with low baseline methylation underwent partial hypermethylation. However, these changes did not consistently correlate with gene silencing or activation. Strikingly, promoters marked by Polycomb (PcG+) in non-tumor tissue were prone to hypermethylation yet often remained transcriptionally active in tumors, a paradox most prominent in transcription factor (TF) genes. In contrast, hypermethylation in PcG- promoters was more consistently associated with transcriptional repression. Our findings suggest that epigenetic plasticity at PcG+ TF gene promoters can override the typically repressive effects of DNA methylation, potentially enabling tumors to maintain or enhance the expression of key regulatory genes. This highlights the importance of PcG occupancy in shaping the functional consequences of methylation changes during colorectal tumorigenesis, warranting deeper investigation into how these epigenetic adaptations drive cancer progression.

bioinformatics↗

bioRxiv2025

Analysis of Microsatellite Instability Intensity in Single-Cell Resolution with scMnT reveals Tumor Heterogeneity in Colorectal Cancer

Although microsatellite instability (MSI) is traditionally regarded as a binary trait, growing evidence indicates that it exists on a continuum, with higher intensity of MSI correlating with better prognosis. However, accurate quantification of MSI intensity is challenging due to the heterogeneous cellular composition of the tumor microenvironment. To this end, we introduce scMnT, a bioinformatic method for identifying MSI cells at single-cell resolution and quantifying MSI intensity based on microsatellite allele lengths. Applying scMnT to scRNA-seq datasets produced robust results and revealed substantial variation in MSI intensity among colorectal cancer patients, with higher MSI intensity correlating with improved responses to immunotherapy. Transcriptomic analyses revealed that MSI intensity-low cancer cells were enriched in goblet signatures, whereas MSI intensity-high cancer cells exhibited strong stem cell characteristics, suggesting a potential link between MSI intensity and cancer cell origin. Our approach provides a novel framework for analyzing MSI at the single-cell level, allowing new opportunities for MSI research.

bioinformatics↗

bioRxiv2025

EZH1 Q571R-mediated chromatin compaction and its oncogenic potential in thyroid cancer

Dysregulation of Polycomb Repressive Complex 2 (PRC2) is established to contribute to cancer. Of its catalytic subunits, EZH1 and EZH2, EZH2 mutations in cancer have been extensively identified and studied, but the role of EZH1 in cancer remains largely unexplored. The recurrent presence of the EZH1Q571R mutation in follicular thyroid cancer suggests its involvement in tumor progression. Using EZH1 ChIP-seq, ATAC-seq, and H3K27me3 CUT&Tag, we demonstrated that EZH1Q571R enhances chromatin binding and compaction and stimulates PRC2-EZH1 catalytic activity, leading to increased H3K27me3 levels and repression of tumor suppressor genes. Purified PRC2-EZH1Q571R demonstrated a significant increase in histone methyltransferase activity compared to PRC2-EZH1WT via enhanced nucleosome binding and DNA compaction. Notably, this effect is particularly observed with EZH1Q571R but only to a lesser extent with the corresponding EZH2Q570R mutation, highlighting it as an EZH1-specific mechanism. We additionally demonstrated PRC2-EZH1Q571R to efficiently methylate H3K27 in pre-existing H3K36me2/3 nucleosomes, disrupting chromatin homeostasis. Our findings provide key insights into the molecular pathogenesis of EZH1Q571R-driven follicular thyroid cancer.

molecular biology↗

bioRxiv2025

Caspase cleavage of APP contributes to amyloid beta-protein induced synaptic injury

BACKGROUNDIncreasing evidence suggests that amyloid beta (A{beta}) lies at the center of Alzheimers Disease (AD) pathology and that synapses are the initial site of damage by A{beta}. Recent studies have also indicated a role for caspases in AD-related synaptic dysfunction and memory loss, but the mechanism(s) through which the caspases act remains elusive. Previous studies in cell culture indicate that cleavage of a caspase site on the intracellular domain of the amyloid precursor protein (APP) protein contributes to A{beta}-induced cell death. However, the role of this cleavage event in synaptic dysfunction has not been established. METHODSThrough a combination of intracellular and extracellular electrophysiological methods and confocal microscopy of dendritic spines, we examined the involvement of caspase-3 and amyloid-precursor protein in A{beta}-mediated synaptic dysfunction. RESULTSHere, we provide evidence that caspase activity at the intracellular domain of APP is required for acute A{beta}-induced depression of glutamatergic synapses. We find that local elevation of A{beta} levels through over-expression of the C-terminal fragment of APP (C99) failed to depress synapses if caspases were inhibited pharmacologically or in tissue lacking caspase-3. To demonstrate a link between these findings to APP, we found that A{beta} failed to depress synaptic transmission or inhibit synaptic plasticity in neurons lacking APP. To specifically test the role of caspase cleavage of the intracellular domain of APP, we introduced a mutation that inhibits caspase cleavage at site 664 to the C99 construct; this construct produced A{beta} but failed to elicit A{beta}-induced synaptic depression or spine loss, and reduced caspase-3 activity. CONCLUSIONTaken together, these results suggest an APP-dependent pathway in which caspases contribute to A{beta}-induced synaptic depression and spine loss via cleavage of APP.

neuroscience↗

bioRxiv2025

Single-cell multiomics identifies both shared and unique features of immune dysfunction in the colon, plasma and stool from individuals diagnosed with Parkinson's disease or inflammatory bowel disease

Parkinsons disease (PD) is the fastest growing neurodegenerative disease in the world1. Gastrointestinal (GI) dysfunction can occur decades before motor impairments and in up to 80% of individuals living with PD2,3,4. We investigated peripheral relationships that may underlie mechanisms along the gut-blood axis that contribute to PD pathogenesis. Single-cell multiomic spatial molecular imaging (SMI) of colonic tissue localized inflammatory injury within epithelial cells that appear to be associated with iron mishandling in both inflammatory bowel disease (IBD) and PD biosamples. We found that both the single-cell SMI of RNA and protein revealed parallel cross-modal dysregulation in the gut epithelium, in both IBD and PD biosamples. These data are accompanied by plasma (PD) and stool (IBD) protein depletion of CCL22. Our findings suggest iron mishandling along the gut barrier likely contributes to systemic inflammation, which may be the catalyst that primes circulating immune cells to body-first PD pathogenesis.

neuroscience↗

bioRxiv2025

Classifying Mild Cognitive Impairment from Normal Cognition: fMRI Complexity Matches Tau PET Performance

BackgroundTau protein accumulation is closely linked to synaptic and neuronal loss in Alzheimers disease (AD), resulting in progressive cognitive decline. Although tau-PET imaging is a direct biomarker of tau pathology, it is costly, carries radiation risks, and is not widely accessible. Resting-state functional MRI (rs-fMRI) complexity--an entropy-based measure of BOLD signal variation--has been proposed as a non-invasive surrogate biomarker of early neuronal dysfunction associated with tau pathology. ObjectivesTo determine whether fMRI-based brain complexity (sample entropy and multiscale entropy) can match or exceed tau-PET in classifying cognitively normal (CN) versus cognitively impaired (MCI/AD) individuals. And to investigate and compare the most influential network regions-of-interest (ROIs) for classification between fMRI complexity and tau-PET, thereby identifying key neuroanatomical correlates of AD-related changes. DesignA cross-sectional study employing 3D convolutional neural network (CNN) classification with five-fold cross-validation and leave-one-network-out analysis. SettingData from the Alzheimers Disease Neuroimaging Initiative (ADNI) database. ParticipantsOne hundred forty-seven older adults (age 72.5 {+/-} 7.5 years), including 95 CN, 45 MCI, and 7 AD. MeasurementsWe created whole-brain complexity maps from rs-fMRI and standardized uptake value ratio (SUVR) maps from tau-PET. Each modality was separately fed into CNN classifiers. Region-based analyses (leave-one-network-out) were performed to identify critical ROIs for classification. ResultsfMRI complexity showed classification accuracy comparable to tau-PET yet surpassed it in F1-score (0.64 vs. 0.61) and area under the curve (AUC; 0.73 vs. 0.67). Salience and dorsal attention networks contributed most to fMRI-based classification, and a dorsal attention network contributed most to tau-PET-based classification. ConclusionsfMRI complexity performs similarly to tau-PET in detecting cognitive impairment related to AD and identifies partially distinct critical ROIs, suggesting an alternative, radiation- free imaging biomarker for earlier detection and broader clinical application.

neuroscience↗

bioRxiv2025

CellPhePy: a Python implementation of the CellPhe toolkit for automated cell phenotyping from microscopy time-lapse videos

We previously developed the CellPhe toolkit1, an open-source R package for automated cell phenotyping from ptychography time-lapse videos. To align with the growing adoption of python-based image analysis tools and to enhance interoperability with widely used software for cell segmentation and tracking, we developed a python implementation of CellPhe, named CellPhePy. CellPhePy preserves all of the core functionality of the original toolkit, including single-cell phenotypic feature extraction, time-series analysis, feature selection and cell type classification. In addition, CellPhePy introduces significant enhancements, such as an improved method for identifying features that differentiate cell populations and extended support for multiclass classification, broadening its analytical capabilities. Notably, the CellPhePy package supports CellPose segmentation and TrackMate tracking, meaning that a set of microscopy images are the only required input with segmentation, tracking and feature extraction fully automated for downstream analysis, without reliance on external applications. The workflows increased flexibility and modularity make it adaptable to different imaging modalities and fully customisable to address specific research questions. CellPhePy can be installed via PyPi or GitHub, and we also provide a CellPhePy GUI to aid user accessibility.

cell biology↗

bioRxiv2024

Hippocampal-cortical interactions in the consolidation of social memory

Episodic memories are initially encoded in the hippocampus and subsequently undergo systems consolidation into the neocortex. The nature of memory stored in the hippocampus and neocortex also differs, with the cortex shown to encode memories in more generalized forms. Although several brain regions are known to encode social information, the specific cortical regions and circuits involved in the consolidation of social memory and the nature of the information encoded in the cortex remain unclear. Using in vivo Ca2+ imaging and optogenetic manipulations, we found that infralimbic (IL) neurons projecting to the nucleus accumbens shell (IL[->]NAcSh) neurons store consolidated social memory. Inactivating IL[->]NAcSh neurons that responded to a familiar conspecific impaired the recognition of other familiar mice including littermates, demonstrating that these neuronal activities support social familiarity. Furthermore, inactivating hippocampal ventral CA1 neurons projecting to the IL disrupted the consolidation of memory for newly familiarized mice while sparing the recognition of littermates. These findings demonstrate the critical role of hippocampal-cortical interactions in the consolidation of social memory.

animal behavior and cognition↗