Biology subjects

Gong, M.

Publications and source records attributed to Gong, M..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

Structural diversity and oligomerization of bacterial ubiquitin-like proteins

Bacteria possess a variety of operons with homology to eukaryotic ubiquitination pathways that encode predicted E1, E2, E3, deubiquitinase, and ubiquitin-like proteins. Some of these pathways have recently been shown to function in anti-bacteriophage immunity, but the biological functions of others remain unknown. Here, we show that ubiquitin-like proteins in two bacterial operon families show surprising architectural diversity, possessing one to three {beta}-grasp domains preceded by diverse N-terminal domains. We find that a large group of bacterial ubiquitin-like proteins possess three {beta}-grasp domains and form homodimers and helical filaments mediated by conserved Ca2+ ion binding sites. Our findings highlight a distinctive mode of self-assembly for ubiquitin-like proteins, and suggest that Ca2+-mediated ubiquitin-like protein filament assembly and/or disassembly enables cells to sense and respond to stress conditions that alter intracellular metal ion concentration.

biochemistry↗

bioRxiv2024

Dual-format attentional template during preparation in human visual cortex

Goal-directed attention relies on forming internal templates of key information relevant for guiding behavior, particularly when preparing for upcoming sensory inputs. However, evidence on how these attentional templates is represented during preparation remains controversial. Here, we combine functional magnetic resonance imaging (fMRI) with an orientation cueing task to isolate preparatory activity from stimulus-evoked responses. Using multivariate pattern analysis, we found decodable information of the to-be-attended orientation during preparation; yet preparatory activity patterns were different from those evoked when actual orientations were perceived. When perturbing the neural activity by means of a visual impulse (pinging technique), the preparatory activity patterns in visual cortex resembled those associated with perceiving these orientations. The observed differential patterns with and without the impulse perturbation suggest a predominantly non-sensory format and a latent, sensory-like format of representation during preparation. Furthermore, the emergence of the sensory-like template coincided with enhanced information connectivity between V1 and frontoparietal areas and was associated with improved behavioral performance. By engaging this dual-format mechanism during preparation, the brain is able to encode both abstract, non-sensory information and more detailed, sensory information, potentially providing advantages for adaptive attentional control. For example, consistent with recent theories of visual search, a predominantly non-sensory template can support the initial guidance and a latent sensory-like format can support prospective stimulus processing.

neuroscience↗

bioRxiv2024

Ultra-resolution Deconvolution of Spatial Transcriptomics Unveils Spatiotemporal Cellular Dynamics in Complex Microenvironments

Immune cells infiltrate tissues in response to exogenous pathogens or spontaneous tumors, generating protective immunity to safeguard tissues. Despite advancements in spatial transcriptomics (ST), the precise spatial distribution and functional specialization of immune cells within tissue microenvironments remain elusive. Here, we introduce an ultra-precision ST deconvolution algorithm (UCASpatial) that enhances the mapping of cell subpopulations to spatial locations by leveraging the contribution of genes indicative of cell identity through entropy-based weighting. Using both in silico and real ST datasets, we demonstrate that UCASpatial improves the robustness and accuracy in identifying low-abundant cell subpopulations and distinguishing transcriptionally heterogeneous cell subpopulations. Applying UCASpatial to human colorectal cancer (CRC), we link genomic alterations in individual cancer clones to multi-cellular characteristics of the tumor immune microenvironment (TIME) and reveal the co-evolution of tumor cells and TIME at a clonal resolution. We show that the copy number gain on chromosome 20q (chr20q-gain) in tumor cells orchestrates a T cell-excluded TIME, indicative of resistance to immunotherapy in CRC, and is associated with tumor-intrinsic human endogenous retrovirus subfamily H (HERV-H) silencing and impaired type I interferon response. In murine wound healing models, we illuminate the spatiotemporal dynamics of individual cell subsets across various stages of the healing process. We discovered that the scarring-healing mice (C57BL/6) exhibited a replacement of Prg4+ chondrogenic progenitors to Igfbp5+ chondrocytes in the wound bed at the regeneration stage, a change not observed in the regenerative strain (MRL/MpJ). The Igfbp5+ chondrocyte, spatially coordinating with Cd36+ Gpnmb+ Il1b- macrophage and Fmod+ fibroblast, forms a pro-fibrotic community associated with regeneration failure. The cell-cell interactions within this three-cell cluster, mediated by the IL11-IL11RA axis, drive the pro-fibrotic community formation and limit regeneration in C57BL/6 mice. Our findings present UCASpatial as a versatile tool for deciphering fine-grained cellular landscapes in ST and exploring intercellular mechanisms in complex and dynamic microenvironments.

bioinformatics↗

bioRxiv2024

Unbiased and comprehensive identification of viral encoded circular RNAs in a large range of viral species and families

Non-coding RNAs play a significant role in viral infection cycles, with recent attention focused on circular RNAs (circRNAs) originating from various viral families. Notably, these circRNAs have been associated with oncogenesis and alterations in viral fitness. However, identifying their expression has proven more challenging than initially anticipated due to unique viral characteristics. This challenge has the potential to impede progress in our understanding of viral circRNAs. Key hurdles in working with viral genomes include: (1) the presence of repetitive regions that can lead to misalignment of sequencing reads, and (2) unconventional splicing mechanisms that deviate from conserved eukaryotic patterns. To address these challenges, we developed vCircTrappist, a bioinformatic pipeline tailored to identify backsplicing events and pinpoint loci expressing circRNAs in RNA sequencing data. Applying this pipeline, we obtained novel insights from both new and existing datasets encompassing a range of animal and human pathogens belonging to Herpesviridae, Retroviridae, Adenoviridae and Orthomyxoviridae families. Subsequent RT-PCR and Sanger sequencings validated the accuracy of the developed bioinformatic tool for a selection of new candidate viral encoded circRNAs. These findings demonstrate that vCircTrappist is an open and unbiased approach for comprehensive identification of virus-derived circRNAs. Significance StatementCircular RNAs (circRNAs) were revealed to have prominent roles in cellular life in the past decade. They were more recently shown to be expressed by viruses, influencing their infectious cycles and host-pathogen relationship. In this context, viruses that were not previously associated with cellular splicing processes are shown to express circRNAs through unknown mechanisms. These non-canonical circRNAs were already shown to be important in the viral cycle and pathogenesis of the viruses they are encoded from. Here, we propose a bioinformatics pipeline that bypasses the limitations of the existing tools in the identification of viral circRNA. Using this pipeline, we discovered numerous candidates and invite the reader to start its own exploration in the realm of viral encoded circRNAs. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=72 SRC="FIGDIR/small/600382v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@1003330org.highwire.dtl.DTLVardef@20d366org.highwire.dtl.DTLVardef@116f38forg.highwire.dtl.DTLVardef@1d04a76_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2024

Renal-Derived Human sPRR Does Not Increase Blood Pressure in High Fat Diet Mice

Obesity is a risk factor for hypertension. Obesity-related hypertension has been associated with elevated plasma soluble prorenin receptor (sPRR) particularly in men. Additionally, renal PRR and sPRR protein expression is upregulated during obesity and diabetes. However, whether renal-derived human sPRR (HsPRR) may influence the intrarenal RAS status to regulate blood pressure and kidney function during obesity has not been investigated. Therefore, we studied the role of collecting duct (CD) derived-HsPRR on blood pressure and kidney function in male and female mice during obesity. Eight-week-old male and female CD-HsPRR mice were placed on a high fat diet for 25 weeks. HsPRR increased renal sPRR concentration but did not change its circulating levels in male and female littermates compared to CTL mice. GFR, water intake and urine flow were not influenced by the CD-HsPRR expression in either sex. Moreover, after 21 weeks of HFD, blood pressure was similar between groups, while only male CD-HsPRR mice showed an impaired pressor response to losartan. In the renal cortex, male CD-HsPRR mice showed increased renin and AT1R mRNA expression associated with increased AQP2, and ENaC subunits protein expression. These data indicate that renal-derived HsPRR induces local upregulation in renin, AT1R and sodium/water transporters in male mice without altering renal hemodynamics or blood pressure. In obese females, CD-HsPRR expression did not affect blood pressure or renal function, which suggests that females may be protected from obesity induced renal function impairment and hypertension.

physiology↗

bioRxiv2023

Heterozygous missense variant in GLI2 impairs human endocrine pancreas development

Missense variants are the most common type of coding genetic variants. Their functional assessment is fundamental for defining any implication in human diseases and may also uncover genes that are essential for human organ development. Here, we applied CRISPR-Cas9 gene editing on human iPSCs to study a heterozygous missense variant in GLI2 identified in a paediatric hyperglycaemic patient and family members. GLI2 is a primary mediator of the Hedgehog pathway, which regulates pancreatic {beta}-cell development in mice. However, neither mutations in GLI2 nor Hedgehog dysregulation have been reported as cause or predisposition to diabetes. A set of isogenic iPSC lines harbouring the missense variant were studied for their ability to differentiate into pancreatic {beta}-like cells. Interestingly, iPSCs carrying the missense variant showed altered GLI2 transcriptional activity and impaired endocrine differentiation. Collectively, our findings underscore an essential role for GLI2 in human endocrine development and identify a novel variant that predisposes to diabetes.

developmental biology↗

bioRxiv2023

Bacterial antiviral defense pathways encode eukaryotic-like ubiquitination systems

Ubiquitination and related pathways play crucial roles in protein homeostasis, signaling, and innate immunity1-3. In these pathways, an enzymatic cascade of E1, E2, and E3 proteins conjugates ubiquitin or a ubiquitin-like protein (Ubl) to targetprotein lysine residues4. Bacteria encode ancient relatives of E1 and Ubl proteins involved in sulfur metabolism5,6 but these proteins do not mediate Ubl-target conjugation, leaving open the question of whether bacteria can perform ubiquitination-like protein conjugation. Here, we demonstrate that a bacterial antiviral immune system encodes a complete ubiquitination pathway. Two structures of a bacterial E1:E2:Ubl complex reveal striking architectural parallels with canonical eukaryotic ubiquitination machinery. The bacterial E1 encodes an N-terminal inactive adenylation domain (IAD) and a C-terminal active adenylation domain (AAD) with a mobile -helical insertion containing the catalytic cysteine (CYS domain). One structure reveals a pre-reaction state with the bacterial Ubl C-terminus positioned for adenylation, and the E1 CYS domain poised nearby for thioester formation. A second structure mimics an E1-to-E2 transthioesterification state, with the E1 CYS domain rotated outward and its catalytic cysteine adjacent to the bound E2. We show that a deubiquitinase (DUB) in the same pathway pre-processes the bacterial Ubl, exposing its C-terminal glycine for adenylation. Finally, we show that the bacterial E1 and E2 collaborate to conjugate Ubl to target-protein lysine residues. Together, these data reveal that bacteria possess bona fide ubiquitination systems with strong mechanistic and architectural parallels to canonical eukaryotic ubiquitination pathways, suggesting that these pathways arose first in bacteria.

biophysics↗

bioRxiv2022

Proteomic Landscape of Human Spermatozoa: Optimized Extraction Method and Application

Human spermatozoa proteomics exposed to some physical, biological or chemical stressors is being explored. However, there is a lack of optimized sample preparation methods to achieve in-depth protein coverage for sperm cells. Meanwhile, it is not clear whether antibiotics can regulate proteins to affect sperm quality. Here, we systematically compared a total of six different protein extraction methods based the combination of three commonly used lysis buffers and physical lysis strategies. The urea buffer combined with ultrasonication (UA_ultrasonication) produced the highest protein extraction rate, leading to the deepest coverage of human sperm proteome (5685 protein groups) from healthy human sperm samples. Since the antibiotics, amoxicillin and clarithromycin, have been widely used against H. pylori infection, we conduct a longitudinal study of sperm proteome via data-independent acquisition tandem mass spectrometry (DIA-MS/MS) on an infected patient during on and off therapy with these two drugs. The semen examination and morphological analysis were performed combined with proteomics analysis. Our results indicated that antibiotics may cause an increase in the sperm concentration and the rate of malformed sperm and disrupt proteome expression in sperm. This work provides an optimized extraction method to characterize the in-depth human sperm proteome and to extend its clinical applications.

biochemistry↗

bioRxiv2022

Pathobionts from chemically disrupted gut microbiota induce insulin-dependent diabetes in mice

BackgroundDysbiotic gut microbiome, genetically predisposed or chemically disrupted, has been linked with insulin-dependent diabetes (IDD) including autoimmune type 1 diabetes (T1D) in both humans and animal models. However, specific IDD-inducing gut bacteria remain to be identified and their casual role in disease development demonstrated via experiments that can fulfill Kochs postulates. ResultsHere, we show that novel gut pathobionts in the Muribaculaceae family, enriched by a low-dose dextran sulfate sodium (DSS) treatment, translocated to the pancreas and caused local inflammation, beta cell destruction and IDD in C57BL/6 mice. Antibiotic removal and transplantation of gut microbiota showed that this low DSS disrupted gut microbiota was both necessary and sufficient to induce IDD. Reduced butyrate content in the gut and decreased gene expression levels of an antimicrobial peptide in the pancreas allowed for the enrichment of members in the Muribaculaceae family in the gut and their translocation to the pancreas. Pure isolate of one such members induced IDD in wildtype germ-free mice on normal diet either alone or in combination with normal gut microbiome after gavaged into stomach and translocated to pancreas. ConclusionThe pathobionts that are chemically enriched in dysbiotic gut microbiota are sufficient to induce insulin-dependent diabetes after translocation to the pancreas. This indicates that IDD can be mainly a microbiome-dependent disease, inspiring the need to search for novel pathobionts for IDD development in humans.

microbiology↗

bioRxiv2022

Gut microbiota-derived tryptamine impairs insulin sensitivity

Gut-microbiota plays a pivotal role in development of type 2 diabetes (T2D), yet the molecular mechanism remains elusive. Here, we show that tryptamine, a microbial metabolite of tryptophan, impairs glucose tolerance and insulin sensitivity. Tryptamine presents a higher level in monkeys with spontaneous diabetes and human with T2D and positively correlated with the glucose tolerance. In parallel, tryptamine level was suppressed by dietary fibers intervention in T2D subjects and negatively correlated with improvement of glucose tolerance. The inhibitory effect of tryptamine on insulin signaling as shown was dependent on a trace amine-associated receptor 1 (TAAR1)-extracellular signal-regulated kinase (ERK) signaling axis. Monoassociation of T2D-associated tryptamine-producing bacteria Ruminococcus gnavus impairs insulin sensitivity in pseudo germ-free mice. Our findings indicate gut microbiota-derived tryptamine contributes to the development of insulin resistance in T2D and may serve as a new target for intervention. Graphical Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

microbiology↗

bioRxiv2021

The first sheep graph pan-genome reveals the spectrum of structural variations and their effects on different tail phenotypes

Structural variations (SVs) are a major contributor to genetic diversity and phenotypic variations, but their prevalence and functions in domestic animals are largely unexplored. Here, we assembled 26 haplotype-resolved genome assemblies from 13 genetically diverse sheep using PacBio HiFi sequencing. We constructed a graph-based ovine pan-genome and discovered 142,422 biallelic insertions and deletions, 7,028 divergent alleles and 13,419 multiallelic variations. We then used a graph-based approach to genotype the biallelic SVs in 684 individuals from 45 domestic breeds and two wild species. Integration with RNA-seq data allows to identify candidate expression-associated SVs. We demonstrate a direct link of SVs and phenotypes by localizing the putative causative insertion in HOXB13 gene responsible for the long-tail trait and identifying multiple large SVs associated with the fat-tail. Beyond generating a benchmark resource for ovine structural variants, our study highlights that animal genetic research will greatly benefit from using a pan-genome graph rather than a single reference genome.

genomics↗

bioRxiv2021

Ancient genomes redate the extinction of Sussemionus, a subgenus of Equus, to late Holocene

The exceptionally-rich fossil record available for the equid family has provided textbook examples of macroevolutionary changes. Horses, asses and zebras represent three extant subgenus of Equus lineage, while the Sussemionus subgenus is another remarkable Equus lineage ranging from North America to Ethiopia in Pleistocene. We sequenced 26 archaeological specimens from northern China in Holocene showing morphological features reminiscent of Equus ovodovi, a species representative of Sussemionus, and further confirmed them as this species by genetic analyses. Thus, we present the first high-quality complete genome of the Sussemionus that we sequenced to 12.0x depth-of-coverage and demonstrate that it survived until [~]3,500 years ago, despite the continued demographic collapse during the Last Glacial Maximum and the great human expansion in East Asia. We also confirmed the Equus phylogenetic tree, and found Sussemionus diverged from the ancestor of non-caballine equids [~]2.3-2.7 Million years ago and admixture events could have taken place between them. Our works suggest the small genetic diversity but not the enhanced inbreeding mainly limited the chances of survival of the species, and illustrates how ancient DNA can inform on extinction dynamics and the long-term resilience of species surviving in cryptic population pockets.

genomics↗

bioRxiv2021

Characterization of SARS-CoV-2 variants B.1.617.1 (Kappa), B.1.617.2 (Delta) and B.1.618 on cell entry, host range, and sensitivity to convalescent plasma and ACE2 decoy receptor

Recently, highly transmissible SARS-CoV-2 variants B.1.617.1 (Kappa), B.1.617.2 (Delta) and B.1.618 were identified in India with mutations within the spike proteins. The spike protein of Kappa contains four mutations E154K, L452R, E484Q and P681R, and Delta contains L452R, T478K and P681R, while B.1.618 spike harbors mutations {Delta}145-146 and E484K. However, it remains unknown whether these variants have altered in their entry efficiency, host tropism, and sensitivity to neutralizing antibodies as well as entry inhibitors. In this study, we found that Kappa, Delta or B.1.618 spike uses human ACE2 with no or slightly increased efficiency, while gains a significantly increased binding affinity with mouse, marmoset and koala ACE2 orthologs, which exhibits limited binding with WT spike. Furthermore, the P618R mutation leads to enhanced spike cleavage, which could facilitate viral entry. In addition, Kappa, Delta and B.1.618 exhibits a reduced sensitivity to neutralization by convalescent sera owning to the mutation of E484Q, T478K, {Delta}145-146 or E484K, but remains sensitive to entry inhibitors-ACE2-lg decoy receptor. Collectively, our study revealed that enhanced human and mouse ACE2 receptor engagement, increased spike cleavage and reduced sensitivity to neutralization antibodies of Kappa, Delta and B.1.618 may contribute to the rapid spread of these variants and expanded host range. Furthermore, our result also highlighted that ACE2-lg could be developed as broad-spectrum antiviral strategy against SARS-CoV-2 variants.

microbiology↗

bioRxiv2021

A missense KCNQ1 Mutation Impairs Insulin Secretion in Neonatal Diabetes

KCNQ1/Kv7 is a voltage-gated K+ channel that regulates heart rhythm, glucose and salt homeostasis. Mutations of KCNQ1 are primarily associated with long-QT syndrome and type 2 diabetes; however, thus far KCNQ1 mutations have not been associated with monogenetic diabetes. Here, we identified a homozygous KCNQ1 missense mutation (R397W) in an individual with permanent neonatal diabetes (PND). To identify the mechanisms that link the mutation to the disease, we introduced the mutation into human embryonic stem cells (hESCs), and used them to derived pancreatic {beta}-like cells (hESC-{beta} cell). In early {beta}-like cells, we observed atypical membrane electrical activity, increased levels of cytoplasmic Ca2+, and a hypersecretion of insulin. Upon extended culture, their insulin secretion decreased and the number of apoptotic cells increased, resulting in a reduction in the numbers of {beta}-like cells. Late-stage {beta}-like cells exhibited a decrease in the expression of metabolic genes, e.g. HNF4, PDX1 and GLUT1, providing a possible mechanism for {beta}-cell dysfunction. Our study identifies KCNQ1 as a novel candidate gene of monogenetic diabetes and shows that KCNQ1 regulates {beta}-cell function and survival.

cell biology↗

bioRxiv2021

Mutation Y453F in the spike protein of SARS-CoV-2 enhances interaction with the mink ACE2 receptor for host adaption

COVID-19 patients transmitted SARS-CoV-2 to minks in the Netherlands in April 2020. Subsequently, the mink-associated virus (miSARS-CoV-2) spilled back over into humans. Genetic sequences of the miSARS-CoV-2 identified a new genetic variant known as "Cluster 5" that contained mutations in the spike protein. However, the functional properties of these "Cluster 5" mutations have not been well established. In this study, we found that the Y453F mutation located in the RBD domain of miSARS-CoV-2 is an adaptive mutation that enhances binding to mink ACE2 and other orthologs of Mustela species without compromising, and even enhancing, its ability to utilize human ACE2 as a receptor for entry. Structural analysis suggested that despite the similarity in the overall binding mode of SARS-CoV-2 RBD to human and mink ACE2, Y34 of mink ACE2 was better suited to interact with a Phe rather than a Tyr at position 453 of the viral RBD due to less steric clash and tighter hydrophobic-driven interaction. Additionally, the Y453F spike exhibited resistance to convalescent serum, posing a risk for vaccine development. Thus, our study suggests that since the initial transmission from humans, SARS-CoV-2 evolved to adapt to the mink host, leading to widespread circulation among minks while still retaining its ability to efficiently utilize human ACE2 for entry, thus allowing for transmission of the miSARS-CoV-2 back into humans. These findings underscore the importance of active surveillance of SARS-CoV-2 evolution in Mustela species and other susceptible hosts in order to prevent future outbreaks.

microbiology↗

bioRxiv2021

Analysis of viral RNA-host protein interactomes enables rapid antiviral drug discovery

RNA viruses including SARS-CoV-2, Ebola virus (EBOV), and Zika virus (ZIKV) constitute a major threat to global public health and society. The interactions between viral genomes and host proteins are essential in the life cycle of RNA viruses and thus provide targets for drug development. However, viral RNA-host protein interactions have remained poorly characterized. Here we applied ChIRP-MS to profile the interactomes of human proteins and the RNA genomes of SARS-CoV-2, EBOV, and ZIKV in infected cells. Integrated interactome analyses revealed interaction patterns that reflect both common and virus-specific host responses, and enabled rapid drug screening to target the vulnerable host factors. We identified Enasidenib as a SARS-CoV-2 specific antiviral agent, and Trifluoperazine and Cepharanthine as broad spectrum antivirals against all three RNA viruses. One Sentence SummaryInteractome analyses of host proteins and the SARS-CoV-2, EBOV, and ZIKV RNA genomes unveil viral biology and drug targets.

microbiology↗

bioRxiv2020

A novel cell culture system modeling the SARS-CoV-2 life cycle

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the global pandemic of COVID-19, and no effective antiviral agents and vaccines are available. SARS-CoV-2 is classified as a biosafety level-3 (BLS-3) agent, impeding the basic research into its biology and the development of effective antivirals. Here, we developed a biosafety level-2 (BSL-2) cell culture system for production of transcription and replication-competent SARS-CoV-2 virus-like-particles (trVLP). This trVLP expresses a reporter gene (GFP) replacing viral nucleocapsid gene (N), which is required for viral genome packaging and virion assembly (SARS-CoV-2-GFP/{Delta}N trVLP). The complete viral life cycle can be achieved and exclusively confined in the cells ectopically expressing SARS-CoV or SARS-CoV-2 N proteins, but not MERS-CoV N. Genetic recombination of N supplied in trans into viral genome was not detected, as evidenced by sequence analysis after one-month serial passages in the N-expressing cells. Moreover, intein-mediated protein trans-splicing approach was utilized to split the viral N gene into two independent vectors, and the ligated viral N protein could function in trans to recapitulate entire viral life cycle, further securing the biosafety of this cell culture model. Based on this BSL-2 SARS-CoV-2 cell culture model, we developed a 96-well format high throughput screening for antivirals discovery. We identified salinomycin, tubeimoside I, monensin sodium, lycorine chloride and nigericin sodium as potent antivirals against SARS-CoV-2 infection. Collectively, we developed a convenient and efficient SARS-CoV-2 reverse genetics tool to dissect the virus life cycle under a BSL-2 condition. This powerful tool should accelerate our understanding of SARS-CoV-2 biology and its antiviral development.

microbiology↗

bioRxiv2020

Experience-dependent alteration of mnemonic representation in early visual cortex and intraparietal sulcus

The ability to discriminate between stimuli relies on a chain of neural operations associated with perception, memory and decision-making. Accumulating studies show learning-dependent plasticity in perception or decision-making, yet whether perceptual learning modifies mnemonic processing remains unclear. Here, we trained participants on an orientation discrimination task, while using fMRI and TMS to separately examine training-induced changes in working memory (WM) representation. Although fMRI decoding revealed orientation-specific neural patterns during delay period in early visual cortex (V1) before, but not after, training, neurodisruption of V1 during delay period led to behavioral deficit in both phases. In contrast, both fMRI decoding and disruptive effect of TMS showed that intraparietal sulcus (IPS) represent WM content after, but not before, training. These results suggest that sensory engagement for WM is relatively independent of training but the coding format may be altered, whereas the involvement of parietal area in WM depends on training.

neuroscience↗