Biology subjects

Dong, C.

Publications and source records attributed to Dong, C..

At least 91 records · Page 5Linked to original sources

bioRxiv2022

New gene evolution with subcellular expression patterns detected in PacBio-sequenced genomes of Drosophila genus

Previous studies described gene age distributions in the focal species of Drosophila melanogaster. Using third-generation PacBio technology to sequence Drosophila species we investigated gene age distribution in the two subgenera of Drosophila. Our work resulted in several discoveries. First, our data detected abundant new genes in entire Drosophila genus. Second, in analysis of subcellular expression, we found that new genes tend to secret into extracellular matrix and are involved in regulation, environmental adaption, and reproductive functions. We also found that extracellular localization for new genes provides a possible environment to promote their fast evolution. Third, old genes tend to be enriched in mitochondrion and the plasma membrane compared with young genes which may support the endosymbiotic theory that mitochondria originate from bacteria that once lived in primitive eukaryotic cells. Fourth, as gene age becomes older the subcellular compartments in which their products reside broadens suggesting that the evolution of new genes in subcellular location drives functional evolution and diversity in Drosophila species. Additionally, based on the analysis of RNA-Seq of two D. melanogaster populations, we determined a universal paradigm of "from specific to constitutive" expression pattern during the evolutionary process of new genes.

evolutionary biology↗

bioRxiv2022

Mesenchymal stromal cells and alpha-1 antitrypsin have a strong synergy in modulating inflammation

Trauma, surgery, and infection can cause severe inflammation. Both dysregulated inflammation intensity and duration can lead to significant tissue injuries, organ dysfunction, mortality, and morbidity. Anti-inflammatory drugs such as steroids and immunosuppressants can dampen inflammation intensity, but they derail inflammation resolution, compromise normal immunity, and have significant adverse effects. The natural inflammation regulator mesenchymal stromal cells (MSCs) have high therapeutic potential because of their unique capabilities to mitigate inflammation intensity, enhance normal immunity, and accelerate inflammation resolution and tissue healing. Furthermore, clinical studies have shown that MSCs are safe and effective. However, they are not potent enough, alone, to completely resolve severe inflammation and injuries. One approach to boost the potency of MSCs is to combine them with synergistic agents. We hypothesized that alpha-1 antitrypsin (A1AT), a plasma protein used clinically and having an excellent safety profile, was a promising candidate for synergism. This investigation examined the efficacy and synergy of MSCs and A1AT to mitigate inflammation and to promote resolution, using in vitro cell cultures and a mouse acute lung injury and inflammation model. We found that the combination of MSCs and A1AT was much more effective than each component alone in i) modulating cytokine releases and inflammatory pathways, ii) inhibiting reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) production by neutrophils, iii) enhancing phagocytosis and, iv) promoting inflammation resolution, tissue healing, and animal survival. Our results support the combined use of MSCs and A1AT for managing severe, acute inflammation.

bioengineering↗

bioRxiv2022

Optimization and redevelopment of single-cell data analysis workflow based on deep generative models

The present single-cell RNA sequencing(scRNA-seq) analysis pipelines require a combination of appropriate normalization, dimension reduction, clustering, and specific-gene analysis algorithms, but the rationale for the choice of these algorithms is relatively subjective because of the lack of ground truth assessment conclusions. As the number of captured single-cells increases, the number of different types of noise cells also increases, which can strongly affect the analysis efficiency. For scRNA-seq, a technology that generates data through multi-process operations, the deep generative model should be a good choice for this type of data analysis, allowing simultaneous estimation of multiple unobservable parameters assumed in the data generation process. Hence, in our study, we sequenced a pool of pre-labeled single cells to obtain a batch of scRNA-seq data with main and fine labels, which was then used to evaluate the clustering and specific-gene analysis methods. Afterward, we applied two deep generative models to infer the probabilities of pseudo and impurity cells. And by stepwise removing the inferred noise cells, the clustering performance and the consistency of different specific-gene analysis methods are both greatly improved. After that, we applied Deep-LDA (a latent Dirichlet allocation-based deep generative model) to scRNA-seq data analysis. And this model takes the count matrix as input, and makes the classification and specific gene optimization process mutually dependent, which has more practical sense and simplifies the analysis workflow. At last, we successfully implemented the model with transferred knowledge to make single-cell annotation and verified its superior performance.

bioinformatics↗

bioRxiv2022

Brain structural covariances in the ageing brain in the UK Biobank

Brain structural covariances or pairwise correlations describe how morphologic properties of brain regions are related to one another across individuals. Although it is reported that brain structural covariance changes during brain development, it is not clear how structural covariance relates to the ageing process. Here we investigated the human brain structural covariances of cortical thickness and subcortical volumes in the ageing brain and their associations with age, cognition, and longevity polygenic risk score (longevity-PRS) by using cross-sectional data from the UK Biobank (N = 42075, aged 45-83 years, M/F=19752 /22323). The sample of participants was divided into 84 non-overlapping groups based on their age. The older the age group, the greater the variability in the whole brain structural covariance. However, there was a differential rate of age-related increase of variance between males and females. The variance of females started lower than those of males and then increased with age with a greater gradient than that of males. There was a consistent and significant enrichment of pairwise correlations within the occipital lobe in ageing process. The cortical thickness and subcortical covariances in older groups were significantly different from those in the youngest group. Sixty-two of the total 528 pairs of cortical thickness correlations and 10 of the total 21 pairs of subcortical volume correlations were significantly associated with age after Bonferroni correction. Specifically, with an increasing age, most decreased cortical thickness correlations were found between the regions within the frontal lobe as well as between the frontal lobe regions and regions in other lobes, while pairwise correlations within occipital lobe regions were all strengthening. Most of these correlations were also associated with global cognition and weakly associated with longevity-PRS. These findings revealed that the structural covariance was not stable during ageing. Given the thinning of the cortex and the volumetric reduction of subcortical structures seen in the ageing process, an increased pairwise correlation between the brain regions in the older brain suggested a strengthened coordinated decline between the brain regions involved. However, some of the brain regions demonstrated a differentiated rate of decline which was shown as the inversed or reduced pairwise correlations between these regions.

neuroscience↗

bioRxiv2022

The frequent occurrence and metabolic versatility of Marinifilaceae bacteria involved in organic matter mineralizationas a key member in global deep sea

Transfer of animal and plant detritus of both terrestrial and marine origins to the deep sea occurs on the global scale. Microorganisms play an important role in mineralizing them therein, yet to identify in situ. Here we report the family Marinifilaceae that occurred as one of the most predominant bacteria thriving on the new inputs of plant and animal biomasses in both marginal and oceanic areas observed via in situ incubation about their differentiation, environmental adaption, and metabolic mechanisms underlying their prevalence in organic matter mineralizing communities. We described the metabolic features and in situ metabolizing activities of different subgroups (tentative genus level), based on the metagenomic and metatranscriptomic data. One representative subgroup MF-2 dominated plant detritus-enriched cultures and specialized in polysaccharide degradation by encoding many hydrolases involved in the hydrolysis of hemicellulose, pectin, starch, cellulose, and polysaccharides containing N-acetyl groups; this subgroup also encodes a manganese superoxide dismutase with the potential of lignin oxidation and possesses complete nitrogen fixation pathway to compensate for the shortage of nitrogen sources inside the plant detritus. In contrast, those dominating the animal tissue-supported microbiomes were more diverse and formed three subgroups, which distinguished themselves from MF-2 in carbon and nitrogen metabolisms. Regardless of differentiation in carbon and nitrogen metabolisms, they share in common in energy conservation through organic fermentation, and anaerobic respiration of diverse electron receptors. These results highlight the role of Marinifilaceae bacteria neglected before in organic matter mineralizing in marine environments coupling carbon and nitrogen cycling with metals and other elements. IMPORTANCEMicrobial mineralization of organic matters has a significant impact on the global biogeochemical cycle. This report confirmed the role of Marinifilaceae in organic degradation in the oceans, with underestimated contribution in the ocean carbon cycling. It is the dominant taxon thriving on plant and animal biomasses in our in situ incubator, as well as in whale- and wood-falls. At least nine subgroups were revealed, and widely distributed in global oceans but merely predominant in organic-rich environments with an average relative abundance of 8.3 %. Different subgroups display a preference for the degradation of different macromolecules (polysaccharides, lignin, and protein) and adapt themselves to the environments via special metabolic metabolisms.

biochemistry↗

bioRxiv2022

Orphan genes are clustered with allorecognition loci and may be involved in incompatibility and speciation in Neurospora

Lineage-specific genes (LSGs) have long been postulated to play roles in the establishment of genetic barriers to intercrossing and speciation. However, there is a lack of working hypotheses as to how they might play that role. In the genome of Neurospora crassa, most of the 670 Neurospora LSGs that are aggregated adjacent to the telomeres are clustered with 61% of the HET-domain genes, which regulate self-recognition and define vegetative incompatibility groups. Among the 342 LSGs that are dynamically expressed during both asexual and sexual phases, 64% were detectable on unusual carbon sources such as furfural and HMF--wildfire-produced chemicals that are a strong inducer of sexual development. Expression of a significant portion of the LSGs was sensitive to light and temperature, factors that regulate the switch from asexual to sexual reproduction. Furthermore, expression of the LSGs was significantly affected in the knockouts of adv-1 and pp-1 that regulate hyphal communication, and expression of more than one quarter of the LSGs was affected by perturbation of the mating locus. Accordingly, we propose a gene-by-environment interaction model encouraging further investigation of the roles of LSGs and HET-domain genes in speciation in Neurospora. This gene-by-environment interaction model emphasizes the roles of the LSGs in response to genetic and environmental factors, leading to the regulation of the switch from the asexual growth and fusion, such that vegetative incompatibility governed by allorecognition promotes allelic homogeneity, sexual reproduction, and outbreeding, whereas VI repression and meiotic recombination promotes allelic polymorphism.

evolutionary biology↗

bioRxiv2022

AdaLiftOver: High-resolution identification of orthologous regulatory elements with adaptive liftOver

Elucidating orthologous regulatory regions for human and model organism genomes is critical for exploiting model organism research and advancing our understanding of results from the genome-wide association studies. Sequence conservation is the de facto approach for finding orthologous non-coding regions between human and model organism genomes. However, existing methods for mapping non-coding genomic regions across species are challenged by the multi-mapping, low precision, and low mapping rate issues. We develop Adaptive liftOver (AdaLiftOver), a large-scale computational tool for identifying orthologous non-coding regions across species. AdaLiftOver builds on the UCSC liftOver framework to extend the query regions and prioritizes the resulting candidate target regions based on the conservation of the epigenomic and the sequence grammar features. Evaluations of AdaLiftOver with multiple case studies, spanning both genomic intervals from epigenome datasets and GWAS SNPs yield AdaLiftOver as a versatile method for deriving hard-to-obtain human epigenome datasets as well as reliably identifying orthologous loci for GWAS SNPs. The R package AdaLiftOver is available from https://github.com/ThomasDCY/AdaLiftOver.

bioinformatics↗

bioRxiv2022

OGG1 inhibitor TH5487 alleviates allergic airway inflammation in mice

Allergic asthma is a complex disease characterized by dyspnea, coughing, chest tightness and airway remodeling, for which there is no cure and is symptomatically treated with inhaled {beta}2-agonist and/or corticosteroids. Molecular mechanisms underlying its complex pathogenesis are not fully understood. However, the 8-oxoguanine DNA glycosylase-1 (OGG1), a DNA repair protein may play a central role, as OGG1 deficiency decreases both innate and allergic inflammatory responses. In this study, administration of TH5487 to mice with OVA-induced allergic airway inflammation significantly decreased goblet cell hyperplasia and mucus production. TH5487 treatment also decreased levels of activated NF-{kappa}B and expression of proinflammatory cytokines resulting in significantly lower recruitment of eosinophils and other immune cells to the lungs. Gene expression profiling of asthma and allergy-related proteins after TH5487 treatment revealed down regulation of Arg1, Mcp1 and Ccl11, and upregulation of the negative regulator of TH2, Bcl6. In addition, the OVA-induced airway hyperresponsiveness was significantly reduced by TH5487 treatment. Taken together, the data presented in this study suggest a clinically relevant utilization of TH5487 for the treatment of allergic inflammation. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/492235v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@2985cdorg.highwire.dtl.DTLVardef@f642corg.highwire.dtl.DTLVardef@79bb1aorg.highwire.dtl.DTLVardef@1eab483_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2022

A phased chromosome-level genome and full mitochondrial sequence for the dikaryotic myrtle rust pathogen, Austropuccinia psidii

The fungal plant pathogen Austropuccinia psidii is spreading globally and causing myrtle rust disease symptoms on plants in the family Myrtaceae. A. psidii is dikaryotic, with two nuclei that do not exchange genetic material during the dominant phase of its life-cycle. Phased and scaffolded genome resources for rust fungi are important for understanding heterozygosity, mechanisms of pathogenicity, pathogen population structure and for determining the likelihood of disease spread. We have assembled a chromosome-level phased genome for the pandemic biotype of A. psidii and, for the first time, show that each nucleus contains 18 chromosomes, in line with other distantly related rust fungi. We show synteny between the two haplo-phased genomes and provide a new tool, ChromSyn, that enables efficient comparisons between chromosomes based on conserved genes. Our genome resource includes a fully assembled and circularised mitochondrial sequence for the pandemic biotype.

genomics↗

bioRxiv2022

Functional plasticity and recurrent cell states of malignant B cells in follicular lymphoma

Follicular lymphoma (FL) derives from malignant transformation of germinal center (GC) B cells. FL malignant B cells are heterogeneous and diverge from their GC B cell-of-origin, but the diversity, function, and location of malignant B cell states remain to be addressed. Based on integrative single-cell RNA-seq, we identified and studied recurrent FL malignant B cell states and dynamics. Most FL B cells spanned a continuum of states from proliferating GC-like to quiescent memory (Mem)-like cell states. That GC-to-Mem axis was the main source of intra-tumor transcriptional heterogeneity. While FL B cell states were independent from subclonal B cell receptor genetics divergence, T follicular helper (TFH) cell-derived signals controlled the transition from Mem-like to GC-like states. GC-like, TFH-activated and Mem-like FL B cells tended to occupy distinct niches within and around tumor follicles. Our study characterizes novel malignant cell states recurrent in B cell lymphomas, and highlights the functional plasticity of malignant B cells.

cancer biology↗

bioRxiv2022

Nrf2 prevents diabetic cardiomyopathy via antioxidation and normalization of glucose and lipid metabolism in the heart

ObjectiveMetabolic disorders and oxidative stress are the main causes of diabetic cardiomyopathy. Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) exerts a powerful antioxidant effect and prevents the progression of diabetic cardiomyopathy. However, the mechanism of its cardiac protection and direct action on cardiomyocytes are not well understood. MethodsIn this study, cardiomyocyte-restricted Nrf2 transgenic mice (Nrf2-TG) were used to directly observe whether cardiomyocyte-specific overexpression of Nrf2 can prevent diabetic cardiomyopathy and correct glucose and lipid metabolism disorders in the heart. ResultsCompared to wild-type (WT) mice, Nrf2-TG mice showed resistance to diabetic cardiomyopathy in a streptozotocin (STZ)-induced type 1 diabetes mouse model. This was primarily manifested as improved echocardiography results as well as reduced myocardial fibrosis, cardiac inflammation, and oxidative stress. ConclusionThese results showed that Nrf2 can directly act on cardiomyocytes to play a cardioprotective role. Mechanistically, the cardioprotective effects of Nrf2 depend on its antioxidation activity, partially through improving glucose and lipid metabolism by targeting the metabolic pathways of Akt/GSK-3 {beta}/HK-II and AMPK/Sirt1/PGC-1.

molecular biology↗

bioRxiv2021

Viral infection engenders bona fide and bystander lung memory B cell subsets through permissive selection

Lung-resident memory B cells (MBCs) provide localized protection against reinfection in the respiratory airways. Currently, the biology of these cells remains largely unexplored. Here, we combined influenza and SARS-CoV-2 infection with fluorescent-reporter mice to identify MBCs regardless of antigen specificity. scRNA-seq analysis and confocal imaging revealed that two main transcriptionally distinct subsets of MBCs colonize the lung peribronchial niche after infection. These subsets arise from different progenitors and are both class-switched, somatically mutated and intrinsically biased in their differentiation fate towards plasma cells. Combined analysis of antigen-specificity and B cell receptor repertoire unveiled a highly permissive selection process that segregates these subsets into "bona fide" virus-specific MBCs and "bystander" MBCs with no apparent specificity for eliciting viruses. Thus, diverse transcriptional programs in MBCs are not linked to specific effector fates but rather to divergent strategies of the immune system to simultaneously provide rapid protection from reinfection while diversifying the initial B cell repertoire.

immunology↗

bioRxiv2021

INFIMA leverages multi-omics model organism data to identify effector genes of human GWAS variants

Genome-wide association studies have revealed many non-coding variants associated with complex traits. However, model organism studies have largely remained as an untapped resource for unveiling the effector genes of non-coding variants. We develop INFIMA, Integrative Fine-Mapping, to pinpoint causal SNPs for Diversity Outbred (DO) mice eQTL by integrating founder mice multi-omics data including ATAC-seq, RNA-seq, footprinting, and in silico mutation analysis. We demonstrate INFIMAs superior performance compared to alternatives with human and mouse chromatin conformation capture datasets. We apply INFIMA to identify novel effector genes for GWAS variants associated with diabetes. The results of the application are available at http://www.statlab.wisc.edu/shiny/INFIMA/

bioinformatics↗

bioRxiv2021

Species-specific gene duplication in Arabidopsis thaliana evolved novel phenotypic effects on morphological traits under strong positive selection

Gene duplication is increasingly recognized as an important mechanism for the origination of new genes, as revealed by comparative genomic analysis. However, the ways in which new duplicate genes contribute to phenotypic evolution remain largely unknown, especially in plants, owing to a lack of experimental and phenotypic data. In this study, we identified the new gene Exov, derived from a partial gene region duplication of its parental gene Exov-L, which is a member of an exonuclease family, into a different chromosome in Arabidopsis thaliana. We experimentally investigated the phenotypic effects of Exov and Exov-L in an attempt to understand how the new gene diverged from the parental copy and contributes to phenotypic evolution. Evolutionary analysis demonstrated that Exov is a species-specific gene that originated within the last 3.5 million years and shows strong signals of positive selection. Unexpectedly, RNAseq analyses reveal that the new gene, despite its young age, has acquired a large number of novel direct and indirect interactions in which the parental gene does not engage. This is consistent with a high, selection-driven substitution rate in the protein sequence encoded by Exov in contrast to the slowly evolving Exov-L, suggesting an important role for Exov in phenotypic evolution. We analyzed phenotypic effects of exov and exov-l single T-DNA-insertion mutants;double exov, exov-l T-DNA insertion mutants; and CRISPR/Cas9-mediated exovcrp and exov-lcrp knockouts on seven morphological traits in both the new and parental genes. We detected significant segregation of morphological changes for all seven traits when assessed in terms of single mutants, as well as morphological changes for seven traits associated with segregation of double exov, exov-l mutants. Substantial divergence of phenotypic effects between new and parental genes was revealed by principal component analyses, suggesting neofunctionalization in the new gene. These results reveal a young gene that plays critical roles in biological processes that underlie morphological and developmental evolution in Arabidopsis thaliana.

evolutionary biology↗

bioRxiv2020

An NF-κB/IRF1 axis programs cDC1s to drive anti-tumor immunity

Conventional type 1 dendritic cells (cDC1s) are critical for anti-tumor immunity. They acquire antigens from dying tumor cells and cross-present them to CD8+ T cells, promoting the expansion of tumor-specific cytotoxic T cells. However, the signaling pathways that govern the anti-tumor functions of cDC1s are poorly understood. We mapped the molecular pathways regulating intra-tumoral cDC1 maturation using single cell RNA sequencing. We identified NF-{kappa}B and IFN pathways as being highly enriched in a subset of functionally mature cDC1s. The specific targeting of NF-{kappa}B or IFN pathways in cDC1s prevented the recruitment and activation of CD8+ T cells and the control of tumor growth. We identified an NF-{kappa}B-dependent IFN{gamma}-regulated gene network in cDC1s, including cytokines and chemokines specialized in the recruitment and activation of cytotoxic T cells. We used single cell transcriptomes to map the trajectory of intra-tumoral cDC1 maturation which revealed the dynamic reprogramming of tumor-infiltrating cDC1s by NF-{kappa}B and IFN signaling pathways. This maturation process was perturbed by specific inactivation of either NF-{kappa}B or IRF1 in cDC1s, resulting in impaired expression of IFN-{gamma}-responsive genes and consequently a failure to efficiently recruit and activate anti-tumoral CD8+ T cells. Finally, we demonstrate the relevance of these findings to cancer patients, showing that activation of the NF-{kappa}B/IRF1 axis in association with cDC1s is linked with improved clinical outcome. The NF-{kappa}B/IRF1 axis in cDC1s may therefore represent an important focal point for the development new diagnostic and therapeutic approaches to improve cancer immunotherapy. One Sentence SummaryNF-{kappa}B and IRF1 coordinate intra-tumoral cDC1 maturation and control of immunogenic tumor growth.

immunology↗

bioRxiv2020

Structural basis for the association of PLEKHA7 with membrane-embedded phosphatidylinositol lipids

PLEKHA7 (pleckstrin homology domain containing family A member 7) plays key roles in intracellular signaling, cytoskeletal organization and cell adhesion, and is associated with multiple human cancers. The interactions of its pleckstrin homology (PH) domain with membrane phosphatidyl-inositol-phosphate (PIP) lipids, are critical for proper cellular localization and function, and their inhibition is an attractive target for anti-cancer therapy. While structural data can provide insights in this area, little is known about the way in which PLEKHA7 and other PH domains interact with membrane-embedded PIPs. Here we report atomic-resolution structures of the PLEHA7 PH domain and describe the molecular mechanism for its recognition of membrane-bound PIPs. Using X-ray crystallography, nuclear magnetic resonance (NMR), molecular dynamics (MD) simulations, and isothermal titration calorimetry (ITC), we show - in atomic-level detail - that the interaction of PLEKHA7 with PIPs is multivalent and induces PIP clustering. The PIP binding mechanism is distinct from a discrete one-to-one interaction. Our findings reveal a central role of the membrane assembly in mediating protein-PIP association and provide a roadmap for the design of PLEKHA7-PIP inhibitors.

biochemistry↗

bioRxiv2020

Effects of long-term closed environment on human saliva microbiota and salivary cytokines

Compared with the normal environment, the microbiota in controlled closed cabins such as space capsules, Lunar/Mars bases have changed. To ensure the health of crewmembers, its necessary to understand the effects of these changes on human symbiotic microorganisms and immunity. In this study, the experimental platform "Lunar Palace 1" with a similar closed and controlled environment was used to research the effects of changed microbial exposure on human saliva microbiota and salivary cytokines. This paper studied on four crewmembers who participated in the third phase of the "Lunar Palace 365" experiment, analyzing the dynamic changes of saliva microbiota and salivary cytokines, and further studying the correlation between salivary cytokines and highly abundant genera. According to our data, the crewmembers saliva microbiota and salivary cytokines fluctuated smoothly throughout the whole experiment. Although a part of microbes increased or decreased some times, they recovered quickly after leaving the controlled environment. The level of IL-6, IL-10 and TNF- in crewmembers saliva decreased from normal environment to the controlled environment, showing reduced levels of oral inflammatory response in crewmembers. In addition, although there were significant individual differences in crewmembers saliva microbiota, sharing living space reduced the difference. Furthermore, the level of TNF- showed a consistent positive correlation with the abundance of Actinomyces and Rothia in the controlled environment, indicating healthy individuals oral mucosal barrier may be sensitive to changes in saliva microbiota. According to the result, semi-sterile environments in controlled closed cabins didnt cause persistent changes in human saliva microbiota and oral immunity. Besides, it provides a new idea for future research on the impact of the controlled environment on crewmembers health, and provides guidance for studying the effect of semi-sterile environments on human immunity based on saliva microbiota. Key pointsO_LISaliva microbes kept stable for individual but got convergent when sharing space; C_LIO_LIThe level of salivary cytokines reduced after entering the controlled environment; C_LIO_LIThere were complex correlations between salivary cytokines and saliva microbes; C_LIO_LIThe crewmembers adapt well to the controlled environment. C_LI

microbiology↗

bioRxiv2020

Distinct place cell dynamics in CA1 and CA3 encode experience in new contexts

When exploring new environments animals form spatial memories that are updated with experience and retrieved upon re-exposure to the same environment. The hippocampus is thought to support these memory processes, but how this is achieved by different subnetworks such as CA1 and CA3 remains unclear. To understand how hippocampal spatial representations emerge and evolve during familiarization, we performed 2-photon calcium imaging in mice running in new virtual environments and compared the trial-to-trial dynamics of place cells in CA1 and CA3 over days. We find that place fields in CA1 emerge rapidly but tend to shift backwards from trial-to-trial and remap upon re-exposure to the environment a day later. In contrast, place fields in CA3 emerge gradually but show more stable trial-to-trial and day-to-day dynamics. These results reflect different roles in CA1 and CA3 in spatial memory processing during familiarization to new environments and constrain the potential mechanisms that support them.

neuroscience↗