Biology subjects

Wang, B.

Publications and source records attributed to Wang, B..

At least 271 records · Page 15Linked to original sources

bioRxiv2024

Identification of leptolin as a novel anti-obesity adipokine

Adipokines are key factors in regulating energy homeostasis. We identified a novel adipokine; we named it Leptolin. In humans, leptolin levels in white adipose tissue were positively corrected with exercise, and negatively associated with body mass index. Leptolin levels were positively correlated with lipolysis-promoting gene expression. Elevated leptolin in plasma of athletes, whereas lowered leptolin in plasma of obese individuals were observed. Leptolin gene-knockout mice exhibited increased adiposity and body weight, and decreased energy expenditure. Leptolin gene-overexpression mice showed obesity-resistant phenotypes. Treatment with leptolin promoted fat mobilization and energy expenditure, and reduced body weight, without affecting food-intake and motor activity. Together, leptolin, a novel adipokine with a capacity to improve metabolic status, may serve as a new therapeutic agent for obesity and metabolic disorders.

physiology↗

bioRxiv2024

Flexible use of conserved motif vocabularies constrains genome access in cell type evolution

Cell types evolve into a hierarchy with related types grouped into families. How cell type diversification is constrained by the stable separation between families over vast evolutionary times remains unknown. Here, integrating single-nucleus multiomic sequencing and deep learning, we show that hundreds of sequence features (motifs) divide into distinct sets associated with accessible genomes of specific cell type families. This division is conserved across highly divergent, early-branching animals including flatworms and cnidarians. While specific interactions between motifs delineate cell type relationships within families, surprisingly, these interactions are not conserved between species. Consistently, while deep learning models trained on one species can predict accessibility of other species sequences, their predictions frequently rely on distinct, but synonymous, motif combinations. We propose that long-term stability of cell type families is maintained through genome access specified by conserved motif sets, or vocabularies, whereas cell types diversify through flexible use of motifs within each set.

evolutionary biology↗

bioRxiv2024

Targeting Liver Epsins Ameliorates Dyslipidemia in Atherosclerosis

BackgroundThe low-density lipoprotein receptor (LDLR) in the liver plays a crucial role in clearing low-density lipoprotein cholesterol (LDL-C) from the bloodstream. This process takes place mainly in the liver. Under atherogenic conditions, Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), secreted by the liver, binds to LDLR on hepatocytes, preventing its recycling and enhancing its lysosomal degradation. This process reduces LDL-C clearance, promoting hypercholesterolemia. Epsins, a family of ubiquitin-binding endocytic adaptors, are key regulators of atherogenesis in lesional cells, including endothelial cells and macrophages. Given epsins canonical role in regulating endocytosis of cell surface receptors, we aimed to determine whether and how liver epsins contribute to PCSK9-mediated LDLR endocytosis and degradation, thereby impairing LDL-C clearance and accelerating atherosclerosis. MethodsLiver-specific epsin knockout (Liver-DKO) atherosclerotic models were generated in ApoE-/- and PCSK9-AAV8-induced atheroprone mice fed on a Western diet. We utilized single-cell RNA sequencing, along with molecular, cellular, and biochemical analyses, to investigate the physiological role of liver epsins in PCSK9-mediated LDLR degradation. Additionally, we explored the therapeutic potential of nanoparticle-encapsulated siRNAs targeting epsins 1 and 2 in ApoE-/- mice with established atherosclerosis. ResultsWestern diet (WD)-induced atherosclerosis was significantly attenuated in ApoE-/-/Liver-DKO mice compared with ApoE-/- controls, as well as in PCSK9-AAV8-induced Liver-DKO mice compared with PCSK9-AAV8-induced wild-type (WT) mice accompanied by reductions in blood cholesterol and triglyceride levels. Mechanistically, single-cell RNA sequencing of hepatocytes and aortas isolated from atherosclerotic ApoE-/- and ApoE-/-/Liver-DKO mice revealed epsin-deficient Ldlrhi hepatocytes with diminished lipogenic potential. Notably, pathway analysis of hepatocytes showed increased LDL particle clearance and enhanced LDLR-cholesterol interactions under WD treatment in ApoE-/-/Liver-DKO mice compared with ApoE-/- controls, correlating with decreased plasma LDL-C levels. Furthermore, pathway analysis of the aortas showed attenuated inflammation and endothelial activation, coupled with reduced lipid uptake, and enhanced cholesterol efflux under WD treatment in ApoE-/-/Liver-DKO mice compared with ApoE-/- controls. Moreover, the absence of liver epsins led to an upregulation of LDLR protein expression in hepatocytes. We further demonstrated that epsins bind LDLR via the ubiquitin-interacting motif (UIM), enabling PCSK9-mediated LDLR degradation. Depleting epsins abolished this degradation, thereby preventing atheroma progression. Lastly, targeting liver epsins with nanoparticle-encapsulated epsins siRNAs effectively ameliorates dyslipidemia and inhibits atherosclerosis progression. These results are consistent with findings showing an increased epsin1 and epsin2 expression in atherosclerotic cardiovascular disease patients. ConclusionsLiver epsins drive atherogenesis by promoting PCSK9-mediated LDLR degradation, thereby elevating circulating LDL-C levels and heightening lesional inflammation. As such, targeting epsins in the liver represents a promising therapeutic strategy to mitigate atherosclerosis by preserving LDLR and enhancing LDL-C clearance in the liver.

cell biology↗

bioRxiv2024

Cellular and molecular networks of intercellular signaling in bone marrow hematopoiesis

Hematopoietic stem and progenitor cells (HSPCs) rely on intercellular signaling to maintain and adjust their production of blood and immune cells. This process occurs in the semi-fluidic bone marrow, hosting dozens of cell types that constantly migrate and interact. To elucidate the dynamic network of cell-cell interaction and signaling transduction underlying hematopoiesis, we developed an algorithm to measure Cell-cell Spatial Interaction Probability (CellSIP) by integrating data on ligand and receptor expression, cell type abundance, and cellular spatial positioning. Using new and published mouse datasets, we validated CellSIP and uncovered signaling transductions indicating feedback mechanisms underlying hematopoiesis. Moreover, we identified significant correlations between signaling pathways across individual HSPCs at the same hematopoiesis stage. These pathway correlations illuminate the organization of cellular and signaling networks underlying hematopoiesis, revealing new regulators through their associations with established ones. The signaling quantification and correlation data are available through the Hematopoiesis Intercellular Signaling Explorer (HISE).

bioinformatics↗

bioRxiv2024

CDK4/6 inhibitors promote senescence-associated lysosomal alterations and enhance sensitivity to lysosomotropic agents in breast cancer

Breast cancer is a leading cause of mortality worldwide. Pharmacological inhibitors of Cyclin- Dependent Kinases (CDK) 4 and 6 (CDK4/6i) inhibit breast cancer growth by inducing a senescent-like state. However, the long-term treatment efficacy remains hindered by the development of drug resistance. Clearance of senescent-like cancer cells may extend the durability of treatment. In this study, we showed that CDK4/6i-treated breast cancer cells exhibit various senescence-associated phenotypes, but remain insensitive to common senolytic compounds. By searching for novel vulnerabilities, we identified a significantly increased lysosomal mass and altered lysosomal structure across various breast cancer cell types upon exposure to CDK4/6i in preclinical systems and clinical specimens. We demonstrated that these lysosomal alterations render breast cancer cells sensitive to lysosomotropic agents, such as L- leucyl-L-leucine methyl ester (LLOMe) and salinomycin. Importantly, sequential treatment with CDK4/6i/lysosomotropic agents effectively reduced the growth of both Hormone Receptor- positive (HR+) and triple-negative breast cancer (TNBC) cells in vivo. This sequential therapeutic strategy offers a promising approach to eliminate CDK4/6i-induced senescent(-like) cells, potentially reducing tumor recurrence and enhancing the overall efficacy of breast cancer therapy.

cancer biology↗

bioRxiv2024

Perinatal liver inflammation is associated with persistent elevation of CXCL10 and its canonical receptor CXCR3 on common myeloid progenitors

Biliary atresia (BA) is a leading cause of liver failure in infants. Despite effective surgical drainage, patients with BA exhibit attenuated immune responses to childhood vaccines, suggesting there are long-lasting alterations to immune function. The perinatal liver is home to hematopoietic stem and progenitor cells (HSPCs) and serves as the epicenter for rapidly progressive and significantly morbid inflammatory diseases like BA. We have previously established the role of neonatal myeloid progenitors in the pathogenesis of perinatal liver inflammation (PLI) and hypothesize that PLI leads to long-term changes to HSPCs in mice that recovered from PLI. To test this hypothesis, we compared the changes that occur to HSPCs and mature myeloid populations in the bone marrow of adult mice during homeostasis and during PLI. Our results demonstrate that HSPCs from animals that recover from PLI ("PLI-recovered") undergo long-term expansion with a reduced proliferative capacity. Notably, PLI leads to persistent activation of common myeloid progenitors through the involvement of CXCL10 and its canonical receptor, CXCR3. Our data suggests that the CXCR3-CXCL10 axis may mediate the changes in HSPCs that lead to altered immune function observed in BA, providing support for a targetable pathway to mitigate the detrimental long-term immune effects observed in patients with BA.

immunology↗

bioRxiv2024

Achieve Handle Level Random Access in Encrypted DNA Archival Storage System via Frequency Dictionary Mapping Coding

DNA as a storage medium has the characteristics of high storage density and durability, but the existing DNA storage system has a high latency, and lacks the consideration of data security. In order to improve the availability of DNA storage, this paper proposes that Frequency Dictionary Mapping Coding (FDMC) implements handle-level random access in DNA Archival storage, and a hybrid e-molecular encryption strategy and multi-level error correction algorithm are provided to ensure data security and integrity. The results of the simulation and wet experiments demonstrate that FDMC can achieve handle-level random access in lossless encrypted DNA storage systems, which balances security and convenience. In terms of read and write consistency, FDMC has significant advantages in storage density and robustness of data recovery. Even in the extreme case of DNA sequence loss of 10%, it can still recover 91.74% of the original data while ensuring storage density above 1.80 bits/nt. In summary, FDMC improves the application range of DNA as a storage medium and bridges the gap between DNA storage and traditional storage modes in the storage and reading of large-scale archives.

bioengineering↗

bioRxiv2024

A multi-model approach defines function altering MECP2 missense variants identified in individuals with autism spectrum disorder

Pathogenic variants in MECP2 commonly lead to Rett syndrome, where MECP2s function as a DNA cytosine methylation reader is believed critical. MECP2 variants are also catalogued in individuals with autism spectrum disorder (ASD), including nine missense variants which had no known clinical significance at the start of this study. To assess these nine variants as risk alleles for ASD, we developed MECP2 variant functional assays using budding yeast and Drosophila. We calibrated these assays with known pathogenic and benign variants. Our data predict that four ASD variants are loss of function and five are functional. Protein destabilization offers insight into the altered function of some of these variants. Notably, yeast and Drosophila lack DNA methylation, yet all Rett pathogenic and ASD variants located in the methyl DNA binding domain that we analyzed proved to be loss of function, suggesting a clinically-relevant role for non-methyl DNA-binding by MECP2.

neuroscience↗

bioRxiv2024

Regulative synthesis of capsular polysaccharides in the pathogenesis of Streptococcus suis

Streptococcus suis (S. suis) is an important zoonotic pathogen causing substantial economic losses in the swine industry. S. suis serotype 2 (SS2) is often isolated from the diseased. S. suis expresses capsular polysaccharide (CPS), a virulence factor crucial for their survival in the blood. However, the role of CPS in the pathogenesis of S. suis is incomplete. Here, we showed a dynamic regulation of CPS in S. suis pathogenesis. In a mouse infection model, an SS2 strain (05ZYH33) was detected in the nasal-associated lymphoid tissue (NALT) and cerebrospinal fluid (CSF) as early as 30 min after intranasal inoculation without bacteremia. Histological analysis revealed that 05ZYH33 in the nasal cavity invaded the olfactory epithelium, resulting in early brain inflammation. Transmission electron microscopy showed that 05ZYH33 isolated from NALT and CSF at early infection time had a thin layer of CPS, and those detected in the blood 5 h post- inoculation showed a much thicker CPS. In addition, adoptive transfer of anti-CPS restricted 05ZYH33 in the blood but not in NALT or CSF. However, an antiserum directed to multiple non-CPS virulence factors (anti-V5) efficiently inhibited 05ZYH33 in NALT, CSF, and blood. Thus, 05ZYH33 colonizes NALT more efficiently without CPS and subsequently invades the meninges through the olfactory nerve system. These findings provide valuable information for the treatment of S. suis infection and the development of vaccines across serotypes of S. suis by targeting CPS-independent immunity.

microbiology↗

bioRxiv2024

Desegregation of neuronal predictive processing

Neural circuits construct internal world-models to guide behavior. The predictive processing framework posits that neural activity signaling sensory predictions and concurrently computing prediction-errors is a signature of those internal models. Here, to understand how the brain generates predictions for complex sensorimotor signals, we investigate the emergence of high-dimensional, multi-modal predictive representations in recurrent networks. We find that robust predictive processing arises in a network with loose excitatory/inhibitory balance. Contrary to previous proposals of functionally specialized cell-types, the network exhibits desegregation of stimulus and prediction-error representations. We confirmed these model predictions by experimentally probing predictive-coding circuits using a rich stimulus-set to violate learned expectations. When constrained by data, our model further reveals and makes concrete testable experimental predictions for the distinct functional roles of excitatory and inhibitory neurons, and of neurons in different layers along a laminar hierarchy, in computing multi-modal predictions. These results together imply that in natural conditions, neural representations of internal models are highly distributed, yet structured to allow flexible readout of behaviorally-relevant information. The generality of our model advances the understanding of computation of internal models across species, by incorporating different types of predictive computations into a unified framework.

neuroscience↗

bioRxiv2024

In-cell structural insight into the asymmetric assembly of central apparatus in mammalian sperm axoneme

In motile cilia or flagella, the axoneme typically exhibits a "9+2" configuration, with the central apparatus (CA) consisting of extensively modified microtubules C1 and C2 to regulate ciliary motility. How C1 and C2 are interconnected asymmetrically remains unknown due to the lack of complete structural model of CA. Here, we utilized the in situ cryo-electron tomography approach to solve the in-cell structure of intact mouse sperm CA at sub-nanometer resolution and built its near-complete atomic model with the aid of AlphaFold2. We identified 39 different CA-associated proteins with 8 never reported from isolated specimen. We assigned the long chain-like ASH-containing proteins CFAP47 and HYDIN responsible for connecting C1 and C2. Sperm from Cfap47-knockout mice displayed a hollowing bridge in the CA structure, correlating with its reduced progressive motility. Our findings elucidate the molecular mechanisms of CA components in ciliary motility, and the implications of their mutations in human ciliopathies.

molecular biology↗

bioRxiv2024

The molecular basis of lamin-specific chromatin interactions

In the cell nucleus, chromatin is anchored to the nuclear lamina, a network of lamin filaments and binding proteins that underly the inner nuclear membrane. The nuclear lamina is involved in chromatin organisation through the interaction of lamina-associated domains (LADs) within the densely packed heterochromatin regions. Employing cryo-focused ion beam (cryo-FIB) milling in conjunction with cryo-electron tomography (cryo-ET), we analysed the distribution of nucleosomes at the lamin-chromatin interface. Depletion of lamin A/C reduced the concentration of nucleosomes at the nuclear periphery, suggesting that lamins are directly involved in the interaction with chromatin. Using cryo-electron microscopy (cryo-EM), we then identified the specific binding motif of the lamin A tail domain that interacts with nucleosomes, distinguishing it from the other lamin isoforms. Furthermore, we examined chromatin structure dynamics using a genome-wide analysis that revealed lamin-dependent macroscopic-scale alterations in gene expression and chromatin remodelling. Our findings provide detailed insights into the dynamic and structural interplay between lamin isoforms and chromatin, molecular interactions which are shaping chromatin architecture and epigenetic regulation.

cell biology↗

bioRxiv2024

Extensive mutual influences of SMC complexes shape 3D genome folding

Mammalian genomes are folded by the distinct actions of SMC complexes which include the chromatin loop-extruding cohesin, the sister-chromatid cohesive cohesin, and the mitotic chromosome-associated condensins. While these complexes function at different stages of the cell cycle, they co-exist on chromatin during the G2/M-phase transition, when genome structure undergoes a dramatic reorganization. Yet, how distinct SMC complexes affect each other and how their mutual interplay orchestrates the dynamic folding of 3D genome remains elusive. Here, we engineered all possible cohesin/condensin configurations on mitotic chromosomes to delineate the concerted, mutual influential action of SMC complexes. We find that: (i) The mitotic SMC complex condensin disrupts the focal accumulation of extrusive-cohesin at CTCF binding sites, thereby promoting the disassembly of interphase TADs and chromatin loops during mitotic progression. Conversely, extrusive-cohesin can impair condensin activity and alter mitotic chromosome helicity. (ii) Condensin diminishes cohesive-cohesin focal enrichment and, conversely, cohesive-cohesin can counteract condensin function and impede mitotic chromosome longitudinal shortening. (iii) The co-presence of extrusive- and cohesive-cohesin synergistically antagonizes condensin function and dramatically delays mitotic chromosome condensation. (iv) Extrusive-cohesin positions cohesive-cohesin at CTCF binding sites. However, cohesive-cohesin by itself is insufficient to mediate the formation of TADs or chromatin loop, implying non-overlapping function with extrusive-cohesin. Instead, cohesive-cohesin restricts chromatin loop expansion, potentially by limiting extrusive-cohesin movement. Collectively, our data describe a comprehensive three-way interplay among major SMC complexes that dynamically sculpts chromatin architecture during cell cycle progression.

cell biology↗

bioRxiv2024

Mesoscale chromatin confinement facilitates target search of pioneer transcription factors in live cells

Pioneer transcription factors (PTFs) possess the unique capability to access closed chromatin regions and initiate cell fate changes, yet the underlying mechanisms remain elusive. Here, we characterized the single-molecule dynamics of PTFs targeting chromatin in living cells, revealing a notable "confined target search" mechanism. PTFs like FOXA1, FOXA2, SOX2, OCT4 and KLF4 sampled chromatin more frequently than non-pioneer factor MYC, alternating between fast free diffusion in the nucleus and slower confined diffusion within mesoscale zones. Super-resolved microscopy showed closed chromatin organized as mesoscale nucleosome-dense domains, confining FOXA2 diffusion locally and enriching its binding. We pinpointed specific histone-interacting disordered regions, distinct from DNA-binding domain, crucial for confined target search kinetics and pioneer activity within closed chromatin. Fusion to other factors enhanced pioneer activity. Kinetic simulations suggested transient confinement could increase target association rate by shortening search time and binding repeatedly. Our findings illuminate how PTFs recognize and exploit closed chromatin organization to access targets, revealing a pivotal aspect of gene regulation.

molecular biology↗

bioRxiv2024

The discovery of phages in the Substantia Nigra and its implication for Parkinson's Disease

BackgroundA century ago, a mystery between virus and Parkinsons disease (PD) was described. Owing to the limitation of human brain biopsy and the challenge of electron microscopy in observing virions in human brain tissue, it has been difficult to study the viral etiology of PD. Recent discovery of virobiota reveals that viruses coexist with humans as symbionts. Newly-developed transcriptomic sequencing and novel bioinformatic approaches for mining the encrypted virome in human transcriptome make it possible to study the relationship between symbiotic viruses and PD. Nevertheless, whether viruses exist in the human substantial nigra (SN), and whether symbiotic viruses underlie PD pathogenesis remain unknown. MethodsWe collected current worldwide human SN transcriptomic datasets from the United States, the United Kingdom, the Netherlands and Switzerland. We used bioinformatic approaches including viruSITE and the Virus-Track to identify the existence of viruses in the SN of patients. The comprehensive RNA sequencing-based virome analysis pipeline was used to characterize the virobiota in the SN. The Pearsons correlation analysis was used to examine the association between the viral RNA fragment counts (VRFC) and PD-related human gene sequencing reads in the SN. The differentially expressed genes (DEGs) in the SN between PD patients and non-PD individuals were used to examine the molecular signatures of PD and also evaluate the impact of symbiotic viruses on the SN. FindingsWe observed the existence of viruses in the human SN. A dysbiosis of virobiota was found in the SN of PD patients. A significant correlation between VRFC and PD-related human gene expression was detected in the SN of PD patients. These PD-related human genes correlated to VRFC were named as the virus-correlated PD-related genes (VPGs). We identified three bacteriophages (phages), including the Proteus phage VB_PmiS-Isfahan, the Escherichia phage phiX174 and the Lactobacillus phage Sha1, that might impair the gene expression of neural cells in the SN of PD patients. The Proteus phage VB_PmiS-Isfahan was a common virus in the SN of patients from the UK, the Netherlands, and Switzerland. VPGs and DEGs together highlighted that the phages might dampen dopamine biosynthesis and weaken cGAS-STING function. InterpretationThis is the first study to discover the involvement of phages in PD pathogenesis. A life-long low symbiotic viral load in the SN may be a contributor to PD pathogenesis. Our findings unlocked the black box between brain virobiota and PD, providing a novel insight into PD etiology from the perspective of phages-human symbiosis.

bioinformatics↗

bioRxiv2024

REAL-TIME VISUALIZATION OF SPLICEOSOME ASSEMBLY REVEALS BASIC PRINCIPLES OF SPLICE SITE SELECTION

The spliceosome is a megadalton protein-RNA complex which removes introns from pre-mRNA, yet the dynamic early assembly steps have not been structurally resolved. Specifically, how the spliceosome selects the correct 3 splice site (3SS) amongst highly similar non-functional sites is not known. Here, we develop a kinetic model of splice site selection based on single-molecule U2AF heterodimer imaging in vitro and in vivo. The model successfully predicts alternative splicing patterns and indicates that 3SS selection occurs while U2AF is in complex with the spliceosome, not during initial binding. This finding indicates the spliceosome operates in a partial kinetic proofreading regime, catalyzed in part by the helicase DDX42, which increases selectivity to the underlying U2AF binding site while still allowing for efficient forward progression. ONE-SENTENCE SUMMARYWe apply a kinetic proofreading model to elucidate how transient U2AF binding leads to high fidelity splice site selection.

biophysics↗

bioRxiv2024

Lacticaseibacillus rhamnosus P118 enhances host tolerance to Salmonella infection by promoting microbe-derived indole metabolites

Salmonella is one of the most common foodborne pathogens, resulting in inflammatory gastroenteritis and frequently accompanied by dysbiosis. Gut commensals, such as Lactobacillus species, have been proven to exhibit broad anti-bacterial activities and protect hosts against pathogenic infections. Here, Lacticaseibacillus rhamnosus strain P118, screened from 290 isolates recovered from fermented yoghurts and healthy piglet intestines using traditional and Caenorhabditis elegans-infection screening strategies, exerts great probiotic properties. Notably, P118 and its supernatant exhibited great antibacterial activities and attenuated C. elegans susceptibility to Salmonella infection. We found that P118 protected mice against Salmonella lethal infections by enhancing colonization resistance, reducing pathogen invasion, alleviating intestinal pro-inflammatory response, and improving microbial dysbiosis and fecal metabolite changes. Microbiota and fecal metabolome analyses suggested P118 administration significantly decreased the relative abundances of potentially harmful microbes (e.g., Salmonella, Anaeroplasma, Klebsiella) and increased the fecal levels of tryptophan and its derivatives (indole, indole-3-acrylic acid, 5-hydroxytryptophan, 5-methoxyindoleacetate). Deterministic processes determined the gut microbial community assembly of P118-pretreated mice. Integrated omics further demonstrated that P118 probiotic activities in enhancing host tolerance to Salmonella infection were mediated by microbe-derived tryptophan/indole metabolites (e.g., indole-3-acrylic acid, indole, tryptophan, 5-methoxyindoleacetic acid, and 5-hydroxytryptophan). Collective results demonstrate that L. rhamnosus P118 could enhance host tolerance to Salmonella infections via various pathways, including direct antibacterial actions, inhibiting Salmonella colonization and invasion, attenuating pro-inflammatory responses of intestinal macrophages, and modulating gut microbiota mediated by microbe-derived indole metabolites.

microbiology↗

bioRxiv2024

Layer-specific reorganization of mnemonic representations in primate retrosplenial cortex during learning

Rapid learning of associations between co-occurring stimuli is essential for episodic memory formation. The retrosplenial cortex (RSC) is strongly interconnected with the hippocampus, and in rodents, the RSC has been shown to support spatial navigation and fear conditioning. Although lesion and neuroimaging studies in humans and macaques have further implicated the RSC in episodic memory, it is unclear how memory representations form and evolve in the RSC. Here we show that representations of memorized contexts in primate RSC form within minutes. These initial representations reorganize as the memory matures, with a shift in the weight of neuronal contributions from superficial to deep RSC layers across an hour and increased local connectivity between deep layer neurons. Because RSC superficial and deep layers represent input and output layers respectively, it suggests that hippocampal inputs provide context information to superficial layers during early learning, and this context information consolidates in deep RSC layers.

neuroscience↗