Biology subjects

Song, J.

Publications and source records attributed to Song, J..

At least 145 records · Page 8Linked to original sources

bioRxiv2024

Chromosome-level genome assembly of milk thistle (Silybum marianum (L.) Gaertn.)

Silybum marianum (L.) Gaertn., commonly known as milk thistle, is a medicinal plant belonging to the Asteraceae family. This plant has been recognized for its medicinal properties for over 2,000 years. However, the genome of this plant remains largely undiscovered, having no reference genome at a chromosomal level. Here, we assembled the chromosome-level genome of S. marianum, allowing for the annotation of 53,552 genes and the identification of transposable elements comprising 58% of the genome. The genome assembly from this study showed 99.1% completeness as determined by BUSCO assessment, while the previous assembly (ASM154182v1) showed 36.7%. Functional annotation of the predicted genes showed 50,329 genes (94% of total genes) with known protein functions in public databases. Comparative genome analysis among Asteraceae plants revealed a striking conservation of collinearity between S. marianum and C. cardunculus . The genomic information generated from this study will be a valuable resource for milk thistle breeding and for use by the larger research community.

genomics↗

bioRxiv2024

Diverse cell death signature based subtypes predict the prognosis and immune characteristics within glioma

BackgroundCell death plays an essential role in the pathogenesis, progression, drug resistance and recurrence of glioma. Although multiple cell death pathways are involved in glioma development, there is lack of a stratification and prognostic modelling for glioma based on the integration of diverse genes for cell deaths. MethodsIn this study, 1254 diverse cell death (DCD)-related genes were assessed using the ConsensusClusterPlus assessment to identify DCD patterns in glioma. CIBERSORT, ssGSEA, and ESTIMATE algorithms were applied to evaluate immune microenvironment differences between subtypes. LASSO Cox regression was used to screen prognosis-related DCD genes, and a risk score model was constructed. TMB, TIDE, immune infiltration, and immunotherapy response was analyzed to evaluate the immune characteristics. ResultsTwo DCD-related subgroups named Clusters 1 and 2, with distinct DCD levels, immune characteristics, and prognoses, were determined from glioma samples. A DCD-based risk score model was developed to assess DCD levels in glioma patients and divide patients into high- and low-risk groups. We found this risk model can be used as an independent prognostic factor for glioma patients. Notably, glioma patients with low risk scores exhibited subdued DCD activity, prolonged survival, and a favorable disposition towards benefiting from immune checkpoint blockade therapies. ConclusionsThis study established a novel signature classification and a risk model by comprehensively analyzing patterns of various DCDs to stratify glioma patients and to predict the prognosis and immune characteristics of glioma. We provided a theoretical basis for the clinical application of DCD-related genes in glioma prognosis and immunotherapy.

bioinformatics↗

bioRxiv2024

Personalized composite scaffolds for accelerated cell- and growth factor-free craniofacial bone regeneration

Approaches to regenerating bone often rely on the integration of biomaterials and biological signals in the form of cells or cytokines. However, from a translational point of view, these approaches face challenges due to the sourcing and quality of the biologic, unpredictable immune responses, complex regulatory paths, and high costs. We describe a simple manufacturing process and a material-centric 3D-printed composite scaffold system (CSS) that offers distinct advantages for clinical translation. The CSS comprises a 3D-printed porous polydiolcitrate-hydroxyapatite composite elastomer infused with a polydiolcitrate-graphene oxide hydrogel composite. Using a continuous liquid interface production 3D printer, we fabricate a precise porous ceramic scaffold with 60% hydroxyapatite content resembling natural bone. The resulting scaffold integrates with a thermoresponsive hydrogel composite, customizable in situ to fit the defect. This hybrid phasic porous CSS mimics the bone microenvironment (inorganic and organic) while allowing independent control of each material phase (rigid and soft). The CSS stimulates osteogenic differentiation in vitro and in vivo. Moreover, it promotes M2 polarization and blood vessel ingrowth, which are crucial for supporting bone formation. Our comprehensive micro-CT analysis revealed that within 4 weeks in a critical-size defect model, the CSS accelerated ECM deposition (8-fold) and mineralized osteoid (69-fold) compared to the untreated. Our material-centric approach delivers impressive osteogenic properties and streamlined manufacturing advantages, potentially expediting clinical application for bone reconstruction surgeries.

bioengineering↗

bioRxiv2024

Deep learning-based Spatial Feature Extraction for Prognostic Prediction of Hepatocellular Carcinoma from Pathological Images

The spatial structures of various cell types in tumor tissues have been demonstrated to be able to provide useful information for the evaluation of the disease progression as well as the responsiveness to targeted therapies. Therefore, powered by machine-learning, several image segmentation methods have been developed to identify tumor-cells, stromal, lymphocytes, etc., in hematoxylin and eosin (H&E) stained pathological images. However, the quantitative and systematic characterization of the spatial structures of various cell types is still challenging. In this work, we first developed a robust procedure based on deep learning to precisely recognize cancer cells, stromal and lymphocytes in H&E-stained pathological images of hepatocellular carcinoma (HCC). In order to quantitatively characterize the composition and spatial arrangement of the tumor microenvironment, we then systematically constructed 109 spatial features based on locations of the 3 major types of cells in the H&E images. Interestingly, we discovered that the absolute values of several spatial features are significantly associated with patient overall survival in two independent patient cohorts, such as the cellular diversity around stromal cells (StrDiv), the average distance between stromal cells (StrDis), the coefficient of variation of the tumor-cell polygon area in the Voronoi diagram (TumCV), etc., based on univariate analysis. In addition, multivariate Cox regress analyses further demonstrated that StrDiv and StrDis are independent survival prognostic factors for HCC patient from The Cancer Genome Atlas Program (TCGA). Furthermore, we demonstrated that a combination analysis with cell spatial features, i.e. StrDiv or TumCV, and another important clinical feature, i.e. microvascular invasion (MVI), can further improve the efficacy of prognostic stratification for patients from the Beijing Hospital cohorts. In summary, the spatial features of tumor microenvironment enabled by the digital image analysis pipeline developed in this work can be effective in patient stratification, which holds the promise for its usage in predicting the therapeutic response of patients in the future.

bioinformatics↗

bioRxiv2024

The kinematics and aerodynamics of hinged wing of honeybees during takeoff

In this study, we utilize a high-speed camera array to meticulously capture the intricate wing kinematics of honeybees during free voluntary takeoffs. This allows us to investigate the variation in kinematic parameters over time. According to the variation of Euler angles, the takeoff process can be categorized into three stages: initial, adjusting, and stable. Our analysis reveals that honeybees typically execute at least 15 wingbeats before taking off, with wing stroke amplitudes exceeding 100 degrees and wingbeat frequencies ranging from 180 to 260 Hz. Significantly, the hinged wing mechanism, connecting the forewing and hindwing via hamuli, undergoes considerable chordwise deformation during this process, with the angle between the fore- and hind-wings surpassing 50 degrees. Notably, the forewing and hindwing maintain a positive camber throughout the wingbeat cycle during takeoff, contributing to the enhanced thrust generation instead of lift, comparing to the flat wings. The positive camber can be passively formed at beginning and ending of each half stroke, but should be actively maintained around middle half-stroke.This study provides valuable insights for aeronautical engineers in the design of flapping wing micro air vehicles, specifically in the effective implementation of hinged wings inspired by the wing motion of honeybees.

biophysics↗

bioRxiv2024

Integrative genomic analysis identifies unique immune environments associated with immunotherapy response in diffuse large B cell lymphoma

Most diffuse large B-cell lymphoma (DLBCL) patients treated with bispecific antibodies (BsAb) or chimeric antigen receptor (CAR) T cells fail to achieve durable treatment responses, underscoring the need for a deeper understanding of mechanisms that regulate the immune environment and response to treatment. Here, an integrative, multi-omic approach was employed to characterize DLBCL immune environments, which effectively segregated DLBCLs into four quadrants - termed DLBCL-immune quadrants (IQ) - defined by cell-of-origin and immune-related gene set expression scores. Recurrent genomic alterations were enriched in each IQ, suggesting that lymphoma cell-intrinsic alterations contribute to orchestrating unique DLBCL immune environments. In relapsed/refractory DLBCL patients, DLBCL-IQ assignment correlated significantly with clinical benefit with the CD20 x CD3 BsAb, mosunetuzumab, but not with CD19-directed CAR T cells. DLBCL-IQ provides a new framework to conceptualize the DLBCL immune landscape and uncovers the differential impact of the endogenous immune environment on outcomes to BsAb and CAR T cell treatment.

cancer biology↗

bioRxiv2024

Single missense mutations in Vi capsule synthesis genes confer hypervirulence to Salmonella Typhi

Many bacterial pathogens, including the human exclusive pathogen Salmonella Typhi, express capsular polysaccharides as a crucial virulence factor. Here, through S. Typhi whole genome sequence analyses and functional studies, we found a list of single point mutations that make S. Typhi hypervirulent. We discovered a single point mutation in the Vi biosynthesis enzymes that control the length or acetylation of Vi is enough to create different capsule variants of S. Typhi. All variant strains are pathogenic, but the hyper-capsule variants are particularly hypervirulent, as demonstrated by the high morbidity and mortality rates observed in infected mice. The hypo-capsule variants have primarily been identified in Africa, whereas the hyper-capsule variants are distributed worldwide. Collectively, these studies increase awareness about the existence of different capsule variants of S. Typhi, establish a solid foundation for numerous future studies on S. Typhi capsule variants, and offer valuable insights into strategies to combat capsulated bacteria.

microbiology↗

bioRxiv2023

Potential clinical value and influence of conductivity in conductive cardiac patches for reducing post-MI arrythmia risks

Conductive cardiac patches can help to restore electric signal conduction of the diseased myocardium after myocardial infarction (MI). However, none of the conductive cardiac patches reported in literature has entered clinical trials. Bench-to-bedside translation of conductive patches has long been hindered by the lack of knowledge of the optimal patch conductivity and deep understanding of the potential clinical benefits and risks in patients. Here, we first prepared conductive cardiac patches with conductivities covering 5 orders of magnitude (10-3-101 S/cm). Disagreeing with the mainstream opinion that patch conductivity close to native myocardium (10-3-10-2 S/cm) is most favorable, our results showed that patches with conductivity two orders of magnitudes higher than native myocardium (10-1-100 S/cm) are most effective in restoring cardiac conduction and lowering inducibility quotient. Conduction velocity (CV) is the essence of the observed results. Rat experiments showed that the low-conductivity patch could increase the CV of infarcted myocardium, but did not fully compensate the mismatch in the CVs of infarct and healthy myocardium. Moderate-conductivity patches could increase myocardial CV to the same level of healthy myocardium, while high-conductivity patches further increased myocardial CV, causing a reversed mismatch. The relationship between patch conductivity and improved CVs in myocardium can be explained by monodomain model theory. Based on the theory, 3D finite element simulation of a MI patient heart predicted that a suitable, patch-improved myocardial CV could reduce the number of reentrants, and stabilize the remaining reentry circuits in the myocardium of the MI patient, which indicated its clinical value.

bioengineering↗

bioRxiv2023

MERITS: a web-based integrated MycobacterialPE/PPE protein database

MotivationPE/PPE proteins, highly abundant in the Mycobacterium genome, play a vital role in virulence and immune modulation. Understanding their functions is key to comprehending the internal mechanisms of Mycobacterium. However, a lack of dedicated resources has limited research into PE/PPE proteins. ResultsAddressing this gap, we introduce MERITS, a comprehensive 3D structure database specifically designed for PE/PPE proteins. MERITS hosts 22,353 non-redundant PE/PPE proteins, encompassing details like physicochemical properties, subcellular localisation, post-translational modification sites, protein functions, and measures of antigenicity, toxicity, and allergenicity. MERITS also includes data on their secondary and tertiary structure, along with other relevant biological information. MERITS is designed to be user-friendly, offering interactive search and data browsing Features to aid researchers in exploring the potential functions of PE/PPE proteins. MERITS is expected to become a crucial resource in the field, aiding in developing new diagnostics and vaccines by elucidating the sequence-structure-functional relationships of PE/PPE proteins. Availability and implementationMERITS is freely accessible at http://merits.unimelb-biotools.cloud.edu.au/.

bioinformatics↗

bioRxiv2023

ConBoTNet: supervised contrastive learning enhances MHC-II peptide binding affinity prediction

Accurate prediction of major histocompatibility complex (MHC)-peptide binding affinity can improve our understanding of cellular immune responses and guide personalized immunotherapies. Nevertheless, the existing deep learning-based approaches for predicting MHC-II peptide interactions fall short of satisfactory performance and offer restricted model interpretability. In this study, we propose a novel deep neural network, termed ConBoTNet, to address the above issues by introducing the designed supervised contrastive learning and bottleneck transformer extractors. Specifically, the supervised contrastive learning pre-training enhances the models representative and generalizable capabilities on MHC-II peptides by pulling positive pairs closer and pushing negative pairs further in the feature space, while the bottleneck transformer module focuses on MHC-II peptide interactions to precisely identify binding cores and anchor positions in an unsupervised manner. Extensive experiments on benchmark datasets under 5-fold cross-validation, leave-one-molecule-out validation, independent testing, and binding core prediction settings highlighted the superiority of our proposed ConBoTNet over current state-of-the-art methods. Data distribution analysis in the latent feature space demonstrated that supervised contrastive learning can aggregate MHC-II-peptide samples with similar affinity labels and learn common features of similar affinity. Additionally, we interpreted the trained neural network by associating the attention weights with peptides and innovatively find both well-established and potential peptide motifs. This work not only introduces an innovative tool for accurately predicting MHC-II peptide affinity, but also provides new insights into a new paradigm for modeling essential biological interactions, advancing data-driven discovery in biomedicine.

bioinformatics↗

bioRxiv2023

Armillaria korhonenii, the sixteenth biological species of Armillaria from China

Armillaria korhonenii, designated as Chinese biological species Q (CBSQ) here, is described as a new species based on phylogenetic and morphological evidence as well as the results of mating tests. This species is the sixteenth biological species of Armillaria reported from China following the discovery of 15 previously known biological species. Phylogenetically, A. korhonenii is the earliest divergent lineage of the genus Armillaria as inferred from the nucleotide sequences of the Elongation Factor 1-Alpha (EF1a). Morphologically, it is characterized by its ellipsoid to elongate basidiospores, yellowish orange to honey yellow pileus with fibrillose squamules. Mating tests indicated that A. korhonenii is a tetrapolar heterogeneous species and is inter-sterile with all the tested species except partial compatibility with CBSH.

microbiology↗

bioRxiv2023

The Lateral Ganglionic Eminence Does Not Generate Cortical Oligodendrocytes

The emergence of myelinating oligodendrocytes represents a pivotal developmental milestone in vertebrates, given their capacity to ensheath axons and facilitate the swift conduction of action potentials. It is widely accepted that cortical oligodendrocyte progenitor cells (OPCs) arise from medial ganglionic eminence (MGE), lateral/caudal ganglionic eminence (LGE/CGE) and cortical radial glial cells (RGCs). Here, we used two different fate mapping strategies to challenge the established notion that the LGE generates cortical OPCs. Furthermore, we used a Cre/loxP-dependent exclusion strategy to reveal that the LGE/CGE-derived OPCs are minimal. Additionally, we showed that specifically eliminating MGE-derived OPCs leads to a significant reduction of cortical OPCs. Together, our findings indicate that the contribution of OPCs from LGE/CGE is minimal, contrary to previous beliefs. These findings provide a new view of the developmental origins of cortical OPCs and a valuable foundation for future research on both normal development and oligodendrocyte-related disease.

developmental biology↗

bioRxiv2023

Study on genetic differentiation of Schistosome japonicum intermediate hosts Oncomelania hupensis robertsoni in hilly regions of China: using the complete mitochondrial genome

ObjectiveOncomelania hupensis robertsoni is the only intermediate host of Schistosoma japonicum in western China, its genetic differentiation directly impacts the susceptibility of Schistosoma japonicum. This study aimed to sequence the complete mitochondrial genome of Oncomelania hupensis robertsoni Yunnan strain and analyze the genetic differentiation of Oncomelania hupensis robertsoni in hilly regions of China. MethodsSamples were from 14 administrative villages in Yunnan Province of China, with 30 Oncomelania hupensis per village, and the complete mitochondrial genome was sequenced. Additional, we retrieved 14 other region Oncomelania hupensis of complete mitochondrial sequences from GenBank, and a comprehensive analysis of the genetic differentiation of Oncomelania hupensis robertsoni was conducted by constructing phylogenetic trees, calculating genetic distances, and analyzing homogeneity. ResultsA total of 26 complete mitochondrial sequences were determined. The length of genome ranged from 15,181 to 15,187 bp, and the base composition of the genome was A+T (67.5%) and G+C content (32.5%). This genome encoded 37 genes, including 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a non-coding region rich in A+T. Using the Philippines genotypes as outgroup, the phylogenetic trees and homology analysis confirmed the existence of two distinct phylogroups, Oncomelania hupensis robertsoni and the remaining 9 provincial genotypes. Oncomelania hupensis robertsoni is subdivided into Oncomelania hupensis robertsoni Yunnan strain and Sichuan strain, with a genetic distance of 0.0834. Oncomelania hupensis robertsoni Yunnan strain is subdivided into two subbranches, "Yunnan North" and "Yunnan South", with a genetic distance of 0.0216, and the samples exhibited over 97% homology. ConclusionOncomelania hupensis robertsoni Yunnan strain exhibits a higher level of genetic homology and clear north-south differentiation, the distribution characteristics were closely associated with watershed distribution. This work reported the first mitochondrial genome of Oncomelania hupensis robertsoni Yunnan strain, which could be used as an important reference genome for Oncomelania hupensis, and also provide a theoretical basis for explaining the distribution pattern of Oncomelania hupensis robertsoni and control of schistosomiasis. Author SummaryOncomelania hupensis (O. hupensis) is the only intermediate host of Schistosoma japonicum (S. japonicum), O. hupensis residing in different geographical regions display morphological differences and genetic variations, along with varying susceptibility to S. japonicum. In this study, we sequenced 26 complete mitochondrial genome of O. hupensis robertsoni Yunnan strain (O. h. r. Yunnan strain), the length of genome ranged from 15,181 to 15,187 bp, and the base composition of the genome was A+T (67.5%) and G+C content (32.5%). This genome encoded 37 genes, including 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a non-coding region rich in A+T. Additional, we retrieved 14 other region O. hupensis of complete mitochondrial sequences from GenBank. The phylogenetic trees and homology analysis confirmed that O. hupensis robertsoni is subdivided into Yunnan strain and Sichuan strain, and O. h. r. Yunnan strain is subdivided into two subbranches, "Yunnan North" and "Yunnan South", the samples exhibited over 97% homology. This work reported the first mitochondrial genome of O. h. r. Yunnan strain, which could be used as an important reference genome for O. hupensis, and also provide a molecular biology-based theoretical foundation for understanding the genetic differentiation of O. hupensis.

genomics↗

bioRxiv2023

Predicting Pseudomonas aeruginosa drug resistance using artificial intelligence and clinical MALDI-TOF mass spectra

Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) is widely used in clinical microbiology laboratories for bacterial identification but its use for prediction of antimicrobial resistance (AMR) remains limited. Here, we used MALDI-TOF MS with artificial intelligence (AI) approaches to successfully predict AMR in Pseudomonas aeruginosa, a priority pathogen with complex AMR mechanisms. The highest performance was achieved for modern {beta}-lactam/{beta}-lactamase inhibitor drugs, namely ceftazidime/avibactam and ceftolozane/tazobactam, with area under the receiver operating characteristic curve (AUROC) of 0.86 and 0.87, respectively. As part of this work, we developed dynamic binning, a feature engineering technique that effectively reduces the high-dimensional feature set and has wide-ranging applicability to MALDI-TOF MS data. Compared to conventional methods, our approach yielded superior performance in 10 of 11 antimicrobials. Moreover, we showcase the efficacy of transfer learning in enhancing the performance for 7 of 11 antimicrobials. By assessing the contribution of features to the models prediction, we identified proteins that may contribute to AMR mechanisms. Our findings demonstrate the potential of combining AI with MALDI-TOF MS as a rapid AMR diagnostic tool for Pseudomonas aeruginosa.

microbiology↗

bioRxiv2023

De novo generation of T-cell receptors with desired epitope-binding property by leveraging a pre-trained large language model

Generating T-cell receptors (TCRs) with desired epitope-binding properties is a fundamental step in the development of immunotherapies, yet heavily relies on laborious and expensive wet experiments. Recent advancements in generative artificial intelligence have demonstrated promising power in protein design and engineering. In this regard, we propose a large language model, termed Epitope-Receptor-Transformer (ERTransformer), for the de novo generation of TCRs with the desired epitope-binding property. ERTransformer is built on EpitopeBERT and ReceptorBERT, which are trained using 1.9 million epitope sequences and 33.1 million TCR sequences, respectively. To demonstrate the model capability, we generate 1000 TCRs for each of the five epitopes with known natural TCRs. The artificial TCRs exhibit low sequence identity (average Bit-score 27.64 with a standard deviation of 1.50) but high biological function similarity (average BLOSUM62 score 32.32 with a standard deviation of 12.01) to natural TCRs. Furthermore, the artificial TCRs are not very structurally identical to natural ones (average RMSD 2.84 [A] with a standard deviation of 1.21 [A]) but exhibit a comparable binding affinity towards the corresponding epitopes. Our work highlights the tremendous potential of applying ERTransformer to generate novel TCRs with desired epitope-binding ability.

bioinformatics↗

bioRxiv2023

Structural basis of transcription: RNA Polymerase II substrate binding and metal coordination at 3.0 A using a free-electron laser

Catalysis and translocation of multi-subunit DNA-directed RNA polymerases underlie all cellular mRNA synthesis. RNA polymerase II (Pol II) synthesizes eukaryotic pre-mRNAs from a DNA template strand buried in its active site. Structural details of catalysis at near atomic resolution and precise arrangement of key active site components have been elusive. Here we present the free electron laser (FEL) structure of a matched ATP-bound Pol II, revealing the full active site interaction network at the highest resolution to date, including the trigger loop (TL) in the closed conformation, bonafide occupancy of both site A and B Mg2+, and a putative third (site C) Mg2+ analogous to that described for some DNA polymerases but not observed previously for cellular RNA polymerases. Molecular dynamics (MD) simulations of the structure indicate that the third Mg2+ is coordinated and stabilized at its observed position. TL residues provide half of the substrate binding pocket while multiple TL/bridge helix (BH) interactions induce conformational changes that could propel translocation upon substrate hydrolysis. Consistent with TL/BH communication, a FEL structure and MD simulations of the hyperactive Rpb1 T834P bridge helix mutant reveals rearrangement of some active site interactions supporting potential plasticity in active site function and long-distance effects on both the width of the central channel and TL conformation, likely underlying its increased elongation rate at the expense of fidelity.

biophysics↗

bioRxiv2023

Structural basis for the allosteric regulation and dynamic assembly of DNMT3B

Oligomerization of DNMT3B, a mammalian de novo DNA methyltransferase, critically regulates its chromatin targeting and DNA methylation activities. However, how the N-terminal PWWP and ADD domains interplay with the C-terminal methyltransferase (MTase) domain in regulating the dynamic assembly of DNMT3B remains unclear. Here, we report the cryo-EM structure of DNMT3B under various oligomerization states. The ADD domain of DNMT3B interacts with the MTase domain to form an autoinhibitory conformation, resembling the previously observed DNMT3A autoinhibition. Our combined structural and biochemical study further identifies a role for the PWWP domain and its associated ICF mutation in the allosteric regulation of DNMT3B tetramer, and a differential functional impact on DNMT3B by potential ADD-H3K4me0 and PWWP-H3K36me3 bindings. In addition, our comparative structural analysis reveals a coupling between DNMT3B oligomerization and folding of its substrate-binding sites. Together, this study provides mechanistic insights into the allosteric regulation and dynamic assembly of DNMT3B.

biochemistry↗

bioRxiv2023

Stimulation of median raphe terminals in dorsal CA2 reduces social investigation in male mice specifically investigating social stimulus of ovariectomized female mice

The cornu ammonis area 2 (CA2) region is essential for social behaviors, especially in social aggression and social memory. Recently, we showed that targeted CA2 stimulation of vasopressin presynaptic fibers from the paraventricular nuclei of hypothalamus strongly enhances social memory in mice. In addition, the CA2 area of the mouse hippocampus receives neuronal inputs from other regions including the septal nuclei, the diagonal bands of Broca, supramammillary nuclei, and median raphe nucleus. However, the functions of these projections have been scarcely investigated. A functional role of median raphe (MR) - CA2 projection is supported by the MR to CA2 projections and 82% reduction of hippocampal serotonin (5-HT) levels following MR lesions. Thus, we investigated the behavioral role of presynaptic fibers from the median raphe nucleus projecting to the dorsal CA2 (dCA2). Here, we demonstrate the optogenetic stimulation of 5-HT projections to dCA2 from the MR do not alter social memory, but instead reduce social interaction. We show that optical stimulation of MR fibers excites interneurons in the stratum radiatum (SR) and stratum lacunosum moleculare (SLM) of CA2 region. Consistent with these observations, we show that bath application of 5-HT increases spontaneous GABA release onto CA2 pyramidal neurons and excites presumed interneurons located in the SR/SLM. This is the first study, to our knowledge, which investigates the direct effect of 5-HT release from terminals onto dCA2 neurons on social behaviors. This highlights the different roles for these inputs (i.e., vasopressin inputs regulating social memory versus serotonin inputs regulating social interaction).

neuroscience↗