Biology subjects

Lee, I.

Publications and source records attributed to Lee, I..

At least 55 records · Page 3Linked to original sources

bioRxiv2023

Gut Microbiome Wellness Index 2 for Enhanced Health Status Prediction from Gut Microbiome Taxonomic Profiles

Recent advancements in human gut microbiome research have revealed its crucial role in shaping innovative predictive healthcare applications. We introduce Gut Microbiome Wellness Index 2 (GMWI2), an advanced iteration of our original GMWI prototype, designed as a robust, disease-agnostic health status indicator based on gut microbiome taxonomic profiles. Our analysis involved pooling existing 8069 stool shotgun metagenome data across a global demographic landscape to effectively capture biological signals linking gut taxonomies to health. GMWI2 achieves a cross-validation balanced accuracy of 80% in distinguishing healthy (no disease) from non-healthy (diseased) individuals and surpasses 90% accuracy for samples with higher confidence (i.e., outside the "reject option"). The enhanced classification accuracy of GMWI2 outperforms both the original GMWI model and traditional species-level -diversity indices, suggesting a more reliable tool for differentiating between healthy and non-healthy phenotypes using gut microbiome data. Furthermore, by reevaluating and reinterpreting previously published data, GMWI2 provides fresh insights into the established understanding of how diet, antibiotic exposure, and fecal microbiota transplantation influence gut health. Looking ahead, GMWI2 represents a timely pivotal tool for evaluating health based on an individuals unique gut microbial composition, paving the way for the early screening of adverse gut health shifts. GMWI2 is offered as an open-source command-line tool, ensuring it is both accessible to and adaptable for researchers interested in the translational applications of human gut microbiome science.

bioinformatics↗

bioRxiv2023

The influence of HLA genetic variation on plasma protein expression

Polymorphism in the human leukocyte antigen class I (HLA-I) and class II (HLA-II) genes is strongly implicated in susceptibility to immune-mediated diseases. However, the molecular effects of HLA genetic variation, including and beyond antigen presentation, remain unclear. Here we examined the effect of HLA genetic variation on the expression of 2940 plasma proteins using imputed HLA variants in 45,330 Europeans in the UK Biobank. We detected 504 proteins (17.1% of all proteins tested) affected by HLA genetic variation (HLA-pQTL), including widespread trans regulation of protein expression by autoimmune disease risk alleles. HLA-pQTL were enriched in gene families related to antigen presentation (e.g. B2M), T cell fate (CD8A; CD4), chemokines (CCL19; CCL21), and NK and macrophage receptors (KIR; LILRA/B), suggesting that HLA polymorphism affects both adaptive and innate immunity. HLA-pQTL also affected expression of diverse proteins with unclear roles in the immune response (e.g. SFTPD, LRPAP1, ENPP6, NPTX1), as well as drug targets for immune-mediated diseases, suggesting complex regulatory roles of the HLA loci. Among trans HLA-pQTL, HLA variants explained 0.1-42.9% of the protein expression variance. Fine-mapping revealed that most HLA-pQTL implicated amino acid positions within the peptide binding groove, suggesting that trans regulation of plasma protein expression by the HLA loci is primarily a consequence of antigen presentation. We also show that HLA-I and II uniquely affect different proteins and biological mechanisms. Altogether, our data reveal the effects of HLA genetic variation on protein expression and aid the interpretation of associations between HLA alleles and immune-mediated diseases.

genetics↗

bioRxiv2023

Selective reactivation of value- and place-dependent information during sharp-wave ripples in the intermediate and dorsal hippocampus

Reactivation of place cells during sharp-wave ripples in the hippocampus is important for memory consolidation. However, whether hippocampal reactivation is affected by the values of events experienced by the animal is largely unknown. Here, we investigated whether place cells in the dorsal (dHP) and intermediate (iHP) hippocampus of rats are differentially reactivated depending on the value associated with a place during the learning of places associated with higher-value rewards in a T-maze. Place cells in the iHP representing the high-value location were reactivated significantly more frequently than those representing the low-value location, characteristics not observed in the dHP. In contrast, the activities of place cells in the dHP coding the routes leading to high-value locations were replayed more than those in the iHP. Our findings suggest that value-based differential reactivation patterns along the septotemporal axis of the hippocampus may play essential roles in optimizing goal-directed spatial learning for maximal reward. TeaserInformation carried by sharp-wave ripples differ qualitatively between the dorsal and intermediate hippocampal regions.

neuroscience↗

bioRxiv2023

Electrocatalytic on-site oxygenation for transplanted cell-based-therapies

Implantable cell therapies and tissue transplants require sufficient oxygen supply to function and are limited by a delay or lack of vascularization from the transplant host1, 2. Exogenous oxygen production can support cells and tissues, such as pancreatic islets and engineered therapeutic cells. Previous oxygenation strategies have targeted gas circulation or decomposition of solid peroxides. These strategies however require bulky implants, transcutaneous supply lines, and are limited in their total oxygen production or regulation3, 4. Readily integrated and controlled production of oxygen has eluded cell therapy devices. Here, we show an electrocatalytic approach that enables bioelectronic control of oxygen generation in complex cellular environments to sustain engineered cell viability and therapy production under hypoxic stress and at high cell densities. Nanostructured sputtered iridium oxide serves as an ideal catalyst for oxygen evolution reaction (OER) at neutral pH. It enables a lower OER onset and shows selective oxygen production without evolution of toxic side products over a 300 mV window of operation. This electrocatalytic on site oxygenator (ecO2) can sustain high cell loadings (>60k cells/mm3) in hypoxic conditions in vitro and in vivo. Our results demonstrate that exogenous oxygen production devices can be readily integrated into bioelectronic platforms and enable high cell loadings in smaller device footprints with broad applicability.

bioengineering↗

bioRxiv2023

Acute myeloid leukemia stratifies as two clinically relevant sphingolipidomic subtypes

Acute myeloid leukemia (AML) is an aggressive disease with complex and heterogeneous biology. Although several genomic classifications have been proposed, there is a growing interest in going beyond genomics to stratify AML. In this study, we profile the sphingolipid family of bioactive molecules in 213 primary AML samples and 30 common human AML cell lines. Using an integrative approach, we identify two distinct sphingolipid subtypes in AML characterized by a reciprocal abundance of hexosylceramide (Hex) and sphingomyelin (SM) species. The two Hex-SM clusters organize diverse samples more robustly than known AML driver mutations and are coupled to latent transcriptional states. Using transcriptomic data, we develop a machine-learning classifier to infer the Hex-SM status of AML cases in TCGA and BeatAML clinical repositories. The analyses show that the sphingolipid subtype with deficient Hex and abundant SM is enriched for leukemic stemness transcriptional programs and comprises an unappreciated high-risk subgroup with poor clinical outcomes. Our sphingolipid-focused examination of AML identifies patients least likely to benefit from standard of care and raises the possibility that sphingolipidomic interventions could switch the subtype of AML patients who otherwise lack targetable alternatives. Key Points1.Sphingolipidomics separates acute myeloid leukemia (AML) patients and cell lines into two subtypes. 2.The subtype with low hexosylceramide and high sphingomyelin defines a new high-risk subtype with poor clinical outcomes.

systems biology↗

bioRxiv2023

Integrative single-cell characterization of frugivory adaptations in the bat kidney and pancreas

Frugivory evolved multiple times in mammals, including bats. However, the cellular and molecular components driving it remain largely unknown. Here, we used integrative single-cell sequencing on insectivorous and frugivorous bat kidneys and pancreases and identified key cell population, gene expression and regulatory element differences associated with frugivorous adaptation that also relate to human disease, particularly diabetes. We found an increase in collecting duct cells and differentially active genes and regulatory elements involved in fluid and electrolyte balance in the frugivore kidney. In the frugivorous pancreas, we observed an increase in endocrine and a decrease in exocrine cells and differences in genes and regulatory elements involved in insulin regulation. Combined, our work provides novel insights into frugivorous adaptation that also could be leveraged for therapeutic purposes.

genomics↗

bioRxiv2023

Mitochondrial genes in the 22q11.2 deleted region regulate neural stem and progenitor cell proliferation

Microdeletion of a 3Mbp region encompassing 45 protein-coding genes at chromosome 22q11.2 (22q11.2DS) predisposes to multiple neurodevelopmental disorders and is one of the greatest genetic risk factors for schizophrenia. Defective mitochondrial function has been hypothesized to contribute to 22q11.2DS pathogenesis; however, which of the six mitochondrial genes contribute to neurodevelopmental phenotypes and their underlying mechanisms remain unresolved. To systematically test 22q11.2DS genes for functional roles in neurodevelopment and behavior, we generated genetic mutants for each of the 37 conserved zebrafish orthologs and performed high throughput behavioral phenotyping using seven behavioral assays. Through this unbiased approach, we identified five single-gene mutants with partially overlapping behavioral phenotypes. Two of these genes, mrpl40 and prodha, encode for mitochondrial proteins and, similar to what we observed in mrpl40 and prodha mutants, pharmacologic inhibition of mitochondrial function during development results in microcephaly. Finally, we show that both mrpl40 and prodha mutants display neural stem and progenitor cell phenotypes, with each gene regulating different neural stem cell populations. Combined, our results demonstrate a critical role for mitochondrial function in neural stem and progenitor cell populations in the developing vertebrate brain and provide compelling evidence that mitochondrial dysfunction during neurodevelopment is linked to brain volume and behavioral phenotypes observed in models of 22q11.2DS.

neuroscience↗

bioRxiv2022

Targeting the BAG-1 family of co-chaperones in lethal prostate cancer.

Therapies that abrogate persistent androgen receptor (AR) signaling in castration resistant prostate cancer (CRPC) remain an unmet clinical need. The N-terminal domain (NTD) of the AR drives transcriptional activity in CRPC but is intrinsically disordered and remains a challenging therapeutic target. Therefore, inhibiting critical co-chaperones, such as BAG-1L, is an attractive alternative strategy. We performed druggability analyses demonstrating the BAG domain to be a challenging drug target. Thio-2, a tool compound, has been reported to bind the BAG domain of BAG-1L and inhibit BAG-1L-mediated AR transactivation. However, despite these data, the mechanism of action of Thio-2 is poorly understood and the BAG domain which is present in all BAG-1 isoforms has not been validated as a therapeutic target. Herein, we demonstrate growth inhibiting activity of Thio-2 in CRPC cell lines and patient derived models with decreased AR genomic binding and AR signaling independent of BAG-1 isoform function. Furthermore, genomic abrogation of BAG-1 isoforms did not recapitulate the described Thio-2 phenotype, and NMR studies suggest that Thio-2 may bind the AR NTD, uncovering a potential alternative mechanism of action, although in the context of low compound solubility. Furthermore, BAG-1 isoform knockout mice are viable and fertile, in contrast to previous studies, and when crossed with prostate cancer mouse models, BAG-1 deletion does not significantly impact prostate cancer development and growth. Overall, these data demonstrate that Thio-2 inhibits AR signaling and growth in CRPC independent of BAG-1 isoforms, and unlike previous studies of the activated AR, therapeutic targeting of the BAG domain requires further validation before being considered a therapeutic strategy for the treatment of CRPC.

molecular biology↗

bioRxiv2022

Engineering a Single Extracellular Vesicle Protein and RNA Assay (siEVPRA) via In Situ Fluorescence Microscopy in a UV Micropatterned Array

The physical and molecular heterogeneity of extracellular vesicles (EVs) confounds bulk biomarker characterization, thus encouraging the development of novel assays capable of profiling EVs at a single-vesicle resolution. Here, we present a single EV (siEV) protein and RNA assay (siEVPRA) to simultaneously detect proteins, messenger RNAs (mRNAs), and microRNAs (miRNAs) in siEVs. The siEVPRA consists of an array of microdomains embedded on a polyethylene glycol (PEG)-coated glass surface produced via UV photopatterning, functionalized with antibodies to target siEV subpopulations. Fluorescently labeled antibodies and RNA-targeting molecular beacons (MBs) were used to generate signals for proteins, mRNAs, and miRNAs on siEVs detected by total internal reflection fluorescence microscopy (TIRFM), outperforming the sensitivities of ELISA and PCR by three orders of magnitude. Using the siEVPRA, we analyzed EVs harvested from glioblastoma (GBM) cell lines and demonstrated vesicular heterogeneity in protein, mRNA, and miRNA expression through colocalization analyses, and validated the results by bulk RNA sequencing. We further demonstrated the clinical utility of the siEVPRA by detecting different mRNAs and miRNAs associated with GBM in patient samples. Together, these results indicate that the siEVPRA provides an effective platform to investigate the heterogeneity of proteins and RNAs in subpopulations of EVs.

bioengineering↗

bioRxiv2022

Phenotypic similarity is a measure of functional redundancy within homologous gene families

Robustness to the impact of mutation can mitigate phenotypes that have the potential to inform gene function. This robustness is often encoded into the genome through gene duplication, among other mechanisms. Duplication is a source of structurally similar genes that can retain some functional overlap as they diverge, and as such contribute to functional redundancy in the face of mutation. While redundancies have been explored in groups of two or three paralogs by generating double and triple mutants, it is unclear to what extent larger homologous gene families contribute to robustness through functional redundancy. Here, we used phenotypic similarity as an indicator of functional redundancy to explore the extent to which homologous gene families contribute to redundancy in function. We hypothesize that, since functional redundancy is more likely to occur within gene families where genes are structurally similar, mutant strains within the same gene families would be more phenotypically similar. We generated 265 single-gene disruptions in four homologous gene families of Myxococcus xanthus, used time-lapse microscopy to generate time series of multicellular development, and developed an image analysis pipeline to compare phenotypic characteristics among different strains. We show that mutant strains cluster by gene family in the phenotypic feature space with principal component analysis, demonstrating that families of homologs can contain extensive functional redundancy networks.

systems biology↗

bioRxiv2022

scHumanNet: a single-cell network analysis platform for the study of cell-type specificity of disease genes

A major challenge in single-cell biology is identifying cell-type-specific gene functions, which may substantially improve precision medicine. Differential expression analysis of genes is a popular, yet insufficient approach, and complementary methods that associate function with cell type are required. Here, we describe scHumanNet (https://github.com/netbiolab/scHumanNet), a single-cell network analysis platform for resolving cellular heterogeneity across gene functions in humans. Based on cell-type-specific networks (CSNs) constructed under the guidance of the HumanNet reference interactome, scHumanNet displayed higher functional relevance to the cellular context than CSNs built by other methods on single-cell transcriptome data. Cellular deconvolution of gene signatures based on network compactness across cell types revealed breast cancer prognostic markers associated with T cells. scHumanNet could also prioritize genes associated with particular cell types using CSN centrality and identified the differential hubness of CSNs between disease and healthy conditions. We demonstrated the usefulness of scHumanNet by uncovering T-cell-specific functional effects of GITR, a prognostic gene for breast cancer, and functional defects in autism spectrum disorder genes specific for inhibitory neurons. These results suggest that scHumanNet will advance our understanding of cell-type specificity across human disease genes.

bioinformatics↗

bioRxiv2022

Accelerated aging induced by stress in experimental murine ocular hypertension.

Aging, a universal process that affects all cells in an organism, is a major risk factor for a group of neuropathies called glaucoma, where elevated intraocular pressure is one of the known stresses affecting the tissue. Our understanding of molecular impact of aging on response to stress in retina is very limited, therefore we developed a new mouse model to approach this question experimentally. Here we show that susceptibility to response to stress increases with age and is primed on epigenetic level. We demonstrate that program activated by hypertension is similar to natural aging, and that one of the earliest pathways activated upon stress is senescence. Finally, we show that multiple instances of pressure elevation cause accelerated aging of young retina as measured on transcriptional and epigenetic level. Our work emphasizes the importance of early diagnosis and prevention as well as age-specific management of age-related eye-diseases, including glaucoma.

molecular biology↗

bioRxiv2022

HiFi Metagenomic Sequencing Enables Assembly of Accurate and Complete Genomes from Human Gut Microbiota

Advances in metagenomic assembly have led to the discovery of genomes belonging to unculturable microorganisms. Metagenome-assembled genomes (MAGs) often suffer from discontinuity and chimerism. Recently, nanopore metagenomic sequencing assembled 20 complete MAGs (cMAGs) from 13 human fecal samples, but with low nucleotide accuracy. Here, we report 102 cMAGs obtained by high-accuracy long-read (HiFi) metagenomic sequencing of five human fecal samples, whose initial circular contigs were filtered for authentic prokaryotic genomes using our bioinformatics workflow. Nucleotide accuracy of the final cMAGs was similar to that of Illumina sequencing. The cMAGs could exceed 6 Mbp and included complete genomes of diverse taxa, including entirely unculturable RF39 and TANB77 orders, whose genomes have not been characterized yet. Moreover, cMAGs revealed that regions hard to assemble by short-read sequencing comprised mostly genomic islands and rRNAs. HiFi metagenomic sequencing will facilitate cataloging accurate and complete genomes of human gut microbiota, including unculturable species.

microbiology↗

bioRxiv2021

Changes of small non-coding RNAs by severe acute respiratory syndrome coronavirus 2 infection

The ongoing pandemic of coronavirus disease 2019 (COVID-19), which results from the rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a significant global public health threat, with molecular mechanisms underlying its pathogenesis largely unknown. Small non-coding RNAs (sncRNAs) are known to play important roles in almost all biological processes. In the context of viral infections, sncRNAs have been shown to regulate the host responses, viral replication, and host-virus interaction. Compared with other subfamilies of sncRNAs, including microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), tRNA-derived RNA fragments (tRFs) are relatively new and emerge as a significant regulator of host-virus interactions. Using T4 PNK-RNA-seq, a modified next-generation sequencing (NGS), we recently found that nasopharyngeal swabs (NPS) samples from SARS-CoV-2 positive and negative subjects show a significant difference in sncRNA profiles. There are about 166 SARS-CoV-2-impacted sncRNAs. Among them, tRFs are the most significantly affected and almost all impacted tRFs are derived from the 5-end of tRNAs (tRF5). Using a modified qRT-PCR, which was recently developed to specifically quantify tRF5s by isolating the tRF signals from its corresponding parent tRNA signals, we validated that tRF5s derived from tRNA GluCTC (tRF5-GluCTC), LysCTT (tRF5-LysCTT), ValCAC (tRF5-ValCAC), CysGCA (tRF5-CysGCA) and GlnCTG (tRF5-GlnCTG) are enhanced in NPS samples of SARS-CoV2 patients and SARS-CoV2-infected airway epithelial cells. In addition to host-derived ncRNAs, we also identified several sncRNAs derived from the virus (svRNAs), among which a svRNA derived from CoV2 genomic site 346 to 382 (sv-CoV2-346) has the highest expression. The induction of both tRFs and sv-CoV2-346 has not been reported previously, as the lack of the 3-OH ends of these sncRNAs prevents them to be detected by routine NGS. In summary, our studies demonstrated the involvement of tRFs in COVID-19 and revealed new CoV2 svRNAs.

microbiology↗

bioRxiv2021

Robust Single-cell Matching and Multi-modalAnalysis Using Shared and Distinct FeaturesReveals Orchestrated Immune Responses

The ability to align individual cellular information from multiple experimental sources, techniques and systems is fundamental for a true systems-level understanding of biological processes. While single-cell transcriptomic studies have transformed our appreciation for the complexities and contributions of diverse cell types to disease, they can be limited in their ability to assess protein-level phenotypic information and beyond. Therefore, matching and integrating single-cell datasets which utilize robust protein measurements across multiple modalities is critical for a deeper understanding of cell states, and signaling pathways particularly within their native tissue context. Current available tools are mainly designed for single-cell transcriptomics matching and integration, and generally rely upon a large number of shared features across datasets for mutual Nearest Neighbor (mNN) matching. This approach is unsuitable when applied to single-cell proteomic datasets, due to the limited number of parameters simultaneously accessed, and lack of shared markers across these experiments. Here, we introduce a novel cell matching algorithm, Matching with pARtIal Overlap (MARIO), that takes into account both shared and distinct features, while consisting of vital filtering steps to avoid sub-optimal matching. MARIO accurately matches and integrates data from different single-cell proteomic and multi-modal methods, including spatial techniques, and has cross-species capabilities. MARIO robustly matched tissue macrophages identified from COVID-19 lung autopsies via CODEX imaging to macrophages recovered from COVID-19 bronchoalveolar lavage fluid via CITE-seq. This cross-platform integrative analysis enabled the identification of unique orchestrated immune responses within the lung of complement-expressing macrophages and their impact on the local tissue microenvironment. MARIO thus provides an analytical framework for unified analysis of single-cell data for a comprehensive understanding of the underlying biological system.

bioinformatics↗

bioRxiv2021

MRGM: a mouse reference gut microbiome reveals a large functional discrepancy for gut bacteria of the same genus between mice and humans

The gut microbiome is associated with human diseases and interacts with dietary components and drugs. In vivo mouse models may be effective for studying diet and drug effects on the gut microbiome. We constructed a mouse reference gut microbiome (MRGM, https://www.mbiomenet.org/MRGM/) that includes newly-assembled genomes from 878 metagenomes. Leveraging samples with ultra-deep metagenomic sequencing (>130 million read pairs), we demonstrated quality improvement in assembled genomes for mouse gut microbes as sequencing depth increased. MRGM provides a catalog of 46,267 non-redundant genomes with [≥]70% completeness and [≤]5% contamination comprising 1,689 representative bacterial species and 15.2 million non-redundant proteins. Importantly, MRGM significantly improved the taxonomic classification rate of sequencing reads from mouse fecal samples compared to previous databases. Using MRGM, we determined that reliable low-abundance taxa profiles of the mouse gut microbiome require sequencing >10 million reads. Despite the high overall functional similarity of the mouse and human gut microbiomes, only ~10% of MRGM species are shared with the human gut microbiome. Although ~80% of MRGM genera are present in the human gut microbiome, ~70% of the shared genera have <40% of core gene content for the respective genus with human counterparts. These suggest that although metabolic processes of the human gut microbiome largely occur in the mouse gut microbiome, functional translations between them according to genus-level taxonomic commonality require caution. Key PointsO_LIMRGM provides 46,267 genomes comprising 1,689 bacterial species of mouse gut microbiome. C_LIO_LIDespite high overlap of genera, functional discrepancy between mouse and human gut microbiota is large. C_LIO_LILineage-specific markers underestimate the completeness of assembled genomes for uncharacterized taxa. C_LI

microbiology↗

bioRxiv2021

Vernalization-triggered expression of the antisense transcript COOLAIR is mediated by CBF genes

To synchronize flowering time with spring, many plants undergo vernalization, a floral-promotion process triggered by exposure to long-term winter cold. In Arabidopsis thaliana, this is achieved through cold-mediated epigenetic silencing of the floral repressor, FLOWERING LOCUS C (FLC). COOLAIR, a cold-induced antisense RNA transcribed from the FLC locus, has been proposed to facilitate FLC silencing. Here, we show that C-repeat (CRT)/dehydration-responsive elements (DREs) at the 3'-end of FLC and CRT/DRE-binding factors (CBFs) are required for cold-mediated expression of COOLAIR. CBFs bind to CRT/DREs at the 3'-end of FLC, both in vitro and in vivo, and CBF levels increase gradually during vernalization. Cold-induced COOLAIR expression is severely impaired in cbfs mutants in which all CBF genes are knocked-out. Conversely, CBF-overexpressing plants show increased COOLAIR levels even at warm temperatures. We show that COOLAIR is induced by CBFs during early stages of vernalization but COOLAIR levels decrease in later phases as FLC chromatin transitions to an inactive state to which CBFs can no longer bind. We also demonstrate that cbfs and FLC{Delta}COOLAIR mutants exhibit a normal vernalization response despite their inability to activate COOLAIR expression during cold, revealing that COOLAIR is not required for the vernalization process.

plant biology↗

bioRxiv2021

Orthogonal representation of task-related information in theta phase-based multiple place fields of single units in the subiculum

The subiculum is positioned at a critical juncture at the interface of the hippocampus with the rest of the brain. However, the exact roles of the subiculum in most hippocampal-dependent memory tasks remain largely unknown. One obstacle to make analytical comparisons of neural firing patterns between the subiculum and hippocampal CA1 is the broad firing fields of the subicular cells. Here, we used spiking phases in relation to theta rhythm to parse the broad firing field of a subicular neuron into multiple subfields to find the unique functional contribution of the subiculum while male rats performed a hippocampal-dependent visual scene memory task. Some of the broad firing fields of the subicular neurons were successfully divided into multiple subfields by using the theta-phase precession cycle. The resulting phase-based fields in the subiculum were more similar to those in CA1 in terms of the field size and phase-precession strength. The new method significantly improved the detection of task-relevant information in subicular cells without affecting the information content represented by CA1 cells. Notably, multiple fields of a single subicular neuron, unlike those in the CA1, could carry heterogeneous task-related information such as visual context and choice response. Our findings suggest that the subicular cells integrate multiple task-related factors by using theta rhythm to associate environmental context with action.

neuroscience↗