Biology subjects

Tang, Y.

Publications and source records attributed to Tang, Y..

At least 217 records · Page 12Linked to original sources

bioRxiv2022

Elucidating the molecular programming of a nonlinear nonribosomal peptide synthetase responsible for fungal siderophore biosynthesis.

Siderophores belonging to the ferrichrome family are essential for the viability of fungal species and play a key role for virulence of numerous pathogenic fungi. Despite their biological significance, our understanding of how these iron-chelating cyclic hexapeptides are assembled by non-ribosomal peptide synthetase (NRPS) assembly lines remains poorly understood, primarily due to the nonlinearity exhibited by the domain architecture. Herein, we report the biochemical characterization of the SidC NRPS, responsible for construction of the intracellular siderophore ferricrocin. In vitro reconstitution of purified SidC revealed its ability to produce ferricrocin and its structural variant, ferrichrome. Application of intact protein mass spectrometry uncovered several non-canonical events during peptidyl siderophore biosynthesis, including inter-modular loading of amino acid substrates and an adenylation domain capable of poly-amide bond formation. This work expands the scope of NRPS programming, allows biosynthetic assignment of ferrichrome NRPSs, and sets the stage for reprogramming towards novel hydroxamate scaffolds.

biochemistry↗

bioRxiv2022

Reconstruct a eukaryotic chromosome arm by de novo design and synthesis

The genome of an organism is inherited from its ancestor and keeps evolving over time, however, how much the current version could be altered remains unknown. Here, we use the left arm of chromosome XII (chrXIIL) as an example to probe the genome plasticity in Saccharomyces cerevisiae. A neochromosome was designed to harbor originally dispersed genes. The essentiality of sequences in chrXIIL was dissected by targeted DNA removal, chromosome truncation and random deletion. Notably, 12 genes were sufficient for survival, while 25 genes are required to retain robust fitness. Next, we demonstrated these genes could be reconstructed using synthetic regulatory sequences and recoded open-reading frames with "one-amino-acid-one-codon" strategy. Finally, we built a neochromsome, which could substitute for chrXIIL for cell viability, with these reconstructed genes. Our work not only highlights the high plasticity of yeast genome, but also illustrates the possibility of making functional chromosomes with completely artificial sequences. HIGHLIGHTSO_LIA neochromosome was designed to facilitate the assembly of exogenous DNA for stable expression in yeast C_LIO_LIThe left arm of chrXII could be minimized to just 12 genes to maintain viability, but additional genes were required to retain robust fitness C_LIO_LIComprehensive recoding and transcriptional refactoring using artificial regulatory sequences produced a functional chromosome arm C_LIO_LIA completely reconstructed neochromosome could replace the chrXIIL to maintain comparable fitness C_LI

synthetic biology↗

bioRxiv2022

IL-10 inhibits STAT1-dependent macrophage accumulation during microbiota-induced colitis

Loss of IL-10R function leads to severe early onset colitis and in murine models is associated with the accumulation of immature inflammatory colonic macrophages. We have shown that IL-10R-deficient colonic macrophages exhibit increased STAT1-dependent gene expression, suggesting that IL-10R-mediated inhibition of STAT1 signaling in newly recruited colonic macrophages might interfere with the development of an inflammatory phenotype. Indeed Stat1-/- mice exhibit defects in colonic macrophage accumulation following Helicobacter hepaticus infection and IL-10R blockade, and this was phenocopied in mice lacking IFNGR, an inducer of STAT1 activation. Radiation chimeras demonstrated that reduced accumulation of STAT1-deficient macrophages was based on a cell-intrinsic defect. Unexpectedly, mixed radiation chimeras generated with both WT and IL-10R-deficient bone marrow indicated that rather than directly interfering with STAT1 function, IL-10R prevents the generation of a cell extrinsic signal that promotes the accumulation of immature macrophages. These results define essential mechanisms controlling inflammatory macrophage accumulation in inflammatory bowel diseases. SummaryIntrinsic STAT1-function drives the accumulation of macrophages within the colon following the loss of IL-10R signaling. IL-10R prevents this STAT1-dependent process through a non-cell autonomous mechanism.

immunology↗

bioRxiv2022

Frataxin deficiency disrupts mitochondrial respiration and pulmonary endothelial cell function

Deficiency of iron-sulfur (Fe-S) clusters promotes metabolic rewiring of the endothelium and the development of pulmonary hypertension (PH) in vivo. Joining a growing number of Fe-S biogenesis proteins critical to pulmonary endothelial function, recent data highlighted that frataxin (FXN) reduction drives Fe-S-dependent genotoxic stress and senescence across multiple types of pulmonary vascular disease. Trinucleotide repeat mutations in the FXN gene cause Friedreichs ataxia, a disease characterized by cardiomyopathy and neurodegeneration. These tissue-specific phenotypes have historically been attributed to mitochondrial reprogramming and oxidative stress. Whether FXN coordinates both nuclear and mitochondrial processes in the endothelium is unknown. Here, we aim to identify the mitochondria-specific effects of FXN deficiency in the endothelium that predispose to pulmonary hypertension. Our data highlight an Fe-S-driven metabolic shift separate from previously described replication stress whereby FXN knockdown diminished mitochondrial respiration and increased glycolysis and oxidative species production. In turn, FXN-deficient endothelial cells exhibited a vasoconstrictive phenotype consistent with PH. These data were observed in both primary pulmonary endothelial cells after pharmacologic inhibition of FXN and inducible pluripotent stem cell-derived endothelial cells from patients with FXN mutations. Altogether, this study defines FXN as a shared upstream driver of pathologic aberrations in both metabolism and genomic stability. Moreover, our study highlights FXN-specific vasoconstriction, suggesting available and future therapies may be beneficial and targeted for PH subtypes with FXN deficiency. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=166 SRC="FIGDIR/small/504849v1_ufig1.gif" ALT="Figure 1"> View larger version (58K): org.highwire.dtl.DTLVardef@12c5568org.highwire.dtl.DTLVardef@19b5f0borg.highwire.dtl.DTLVardef@17d0157org.highwire.dtl.DTLVardef@1e323a0_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2022

MHA, an interactive website for scRNA-seq data of male genitourinary development and disease

The development of single-cell sequencing technology has expanded the understanding of cell heterogeneity and disease progression in the male genitourinary system. However, complex processing processes and unprofessional analytical annotations limit the daily use and wildly sharing of published datasets. Here, we describe the Male Health Atlas (MHA), an easy-to-operate online visual website focused on the male genitourinary system, allowing researchers to quickly search for expression patterns of one or multiple genes, and dynamic changes of gene expression during tissue development or under pathological states. At present, the MHA includes nine objects, two species, five types of male genitourinary tissues/organs, and 258,777 single-cell profiles. Compared with other single-cell databases, the MHA has the following advantages: (1) It is easy to operate, and users can complete retrieval and output of results within 5 min without any bioinformatics skills; (2) The selection and analysis of data are under professional supervision of researchers in the male genitourinary field; (3) It contains most of the main male-specific organs and will continue to be updated; (4) MHA provides multi-dimensional output patterns, including tSNE/UMAP, violin, and bubble plot output for displaying single or multiple genes. MHA is the first single-cell database website in the field of andrology and male reproduction, providing researchers with scRNA-seq resources and an accessible tool. MHA is freely available at http://malehealthatlas.cn/.

molecular biology↗

bioRxiv2022

linc-mipep and linc-wrb encode micropeptides that regulate chromatin accessibility in vertebrate-specific neural cells

Thousands of long intergenic non-coding RNAs (lincRNAs) are transcribed throughout the vertebrate genome. A subset of lincRNAs enriched in developing brains has recently been found to contain cryptic open reading frames and are speculated to encode micropeptides. However, systematic identification and functional assessment of these transcripts have been hindered by technical challenges caused by their small size. Here we show that two putative lincRNAs (linc-mipep and linc-wrb) encode micropeptides with homology to the vertebrate-specific chromatin architectural protein, Hmgn1, and demonstrate that they are required for development of vertebrate-specific brain cell types. Specifically, we show that NMDA receptor-mediated pathways are dysregulated in zebrafish lacking these micropeptides and that their loss preferentially alters the gene regulatory networks that establish cerebellar cells and oligodendrocytes - evolutionarily newer cell types that develop postnatally in humans. These findings highlight the power of screening for unexplored micropeptide functions by revealing a key missing link in the evolution of vertebrate brain cell development and illustrating a genetic basis for how some neural cell types are more susceptible to chromatin disruptions, with implications for neurodevelopmental disorders and disease.

developmental biology↗

bioRxiv2022

Interpretable XGBoost-SHAP model predicts the nanoparticles delivery and reveals its interaction with tumor genomic profiles

Understanding the complex interaction between nanoparticles (NPs) and tumors in vivo and how it dominates the delivery efficacy of NPs is critical for the translation of nanomedicine. Herein, we proposed an interpretable XGBoost-SHAP model by integrating the information of NPs physicochemical properties and tumor genomic profile to predict the delivery efficacy. The correlation coefficients were > 0.99 for all training sets, and 0.830, 0.839, and 0.741 for the prediction of maximum delivery efficacy (DEmax), delivery efficacy at 24 h (DE24), and delivery efficacy at 168 (DE168) for test sets. The analysis of the feature importance revealed that the tumor genomic mutations and their interaction with NPs properties played an important role in the delivery of NPs. The functional profile of the NP-delivery-related genes was further explored through gene ontology enrichment analysis. Our work provides a method to accurately predict the delivery efficacy of NPs to heterogeneous tumors and highlights the power of simultaneously using omics data and interpretable machine learning algorithms for discovering the interaction between NPs and tumors, which is important for the development of precision nanomedicine.

bioengineering↗

bioRxiv2022

Midkine expression by stem-like tumor cells drives persistence to mTOR inhibition and rewires the microenvironment toward an immune-suppressive state

mTORC1 regulates cell metabolism to enable cell proliferation, and is hyperactive in multiple cancer types1, 2. Here, we performed integrative analysis of single cell transcriptomic profiling, paired T cell receptor (TCR) sequencing, and spatial transcriptomic profiling on Tuberous Sclerosis Complex (TSC) associated tumors with mTORC1 hyperactivity, and identified a stem-like tumor cell state (SLS) linked to T cell dysfunction via tumor-modulated immunosuppressive macrophages. Rapamycin and its derivatives (rapalogs) are the primary treatments for TSC tumors, and the stem-like tumor cells showed rapamycin resistance in vitro, reminiscent of the cytostatic effects of these drugs in patients. The pro-angiogenic factor midkine (MDK) was highly expressed by the SLS population, and associated with enrichment of endothelial cells in SLS-dominant samples. Inhibition of MDK showed synergistic benefit with rapamycin in reducing the growth of TSC cell lines in vitro and in vivo. In aggregate, this study suggests an autocrine rapamycin resistance mechanism and a paracrine tumor survival mechanism via immune suppression adopted by the stem-like state tumor cells with mTORC1 hyperactivity. We also provide a comprehensive resource to advance the understanding of TSC and potentially other mTORC1-hyperactive tumors.

cancer biology↗

bioRxiv2022

Site-specific validation and quantification of RNA 2'-O-methylation by qPCR with RNase H

RNA 2'-O-methylation, one of the most abundant modifications on RNAs, is crucial for diverse intracellular biological processes. In the past several years, several high-throughput screening methods have been developed, resulting in the identification of thousands of new 2'-O-methylation (Nm) sites. However, due to the high variability in these high-throughput methods, accurate and rapid low-throughput validation assays are needed to confirm and quantify the 2'-O-methylation status of screened candidate sites. Although several low-throughput Nm site detection methods have been reported, precise location and quantitative assays are still challenging to achieve. Based on the characteristic that RNase H would be inhibited by Nm modification, we developed Nm-VAQ (site-specific 2'-O-methylation (Nm) Validation and Absolute Quantification resolution). In this study, with multiple tests of reagents and conditions, Nm-VAQ was established with a chimera probe of RNA/DNA, RNase H site-specific cleavage, and qRT-PCR, which demonstrated precise absolute quantification of modification ratios and methylation copy numbers. With the help of Nm-VAQ, the 2'-O-methylation status of 5 sites in rRNA was evaluated.

biochemistry↗

bioRxiv2022

Visualizing cell-cell interactions between immune effector and tumor cells induced by antibodies using a proximity-dependent biosensor system

Background and PurposeDespite the promising results of therapeutic antibodies in engaging the immune system to eliminate malignant cells, many aspects of the complex interplay between immune cells and cancer cells during antibody therapy remain incompletely understood. This study aimed to develop a biosensor system that can evaluate direct cell-cell contact and interactions between immune effector and target cells induced by therapeutic antibodies in physiologically relevant environments. Experimental ApproachThe system uses two structural complementary luciferase units (SmBit and LgBit) expressed on the respective membranes of immune effector and target cells. Upon cell-cell contact, the two subunits form active NanoLuc, generating a luminescent signal, allowing for real-time monitoring of cell-cell interactions and quantitatively assessing the pharmacological effects of therapeutic antibodies. Key ResultsWe optimized the system to ensure selectivity by adjusting the spacer lengths between two luciferase units to minimize interference from nonspecific intercellular contact. The system was able to quantitatively and longitudinally monitor cell-cell interactions between NK and target cells induced by rituximab and between T and target cells induced by blinatumomab in a three-dimensional cell culture system. The observation that NK cells exhibited faster interactions with target cells compared to T cells is intriguing and suggests potential differences in the mechanisms or kinetics of cell-cell interactions between different types of effector cells and tumor cells. Conclusions and ImplicationsThe biosensor system has the potential for broad applications to optimize antibody pharmacology and efficacy in various therapeutic areas through a deeper understanding of antibody-mediated cell-cell interactions. What is already knownO_LITherapeutic antibodies can activate the immune system to elicit cytotoxicity through inducing cell-cell interactions between immune and tumor cells. C_LIO_LIApproaches for longitudinally evaluating cell-cell interaction induced by therapeutic antibodies remain limited. C_LI What does this study addO_LIThis study develops a biosensor system for detecting cell-cell interactions induced by therapeutic antibodies in a longitudinal manner. C_LIO_LIThe system is able to monitor cell-cell interactions between NK and target cells, as well as between T and target cells, in a three-dimensional cell culture system. C_LI What is the clinical significanceO_LIThe biosensor system has the potential for broad applications in the field of antibody pharmacology by providing a deeper understanding of antibody-mediated cell-cell interactions and their dynamics. C_LI

pharmacology and toxicology↗

bioRxiv2022

Disrupting ACE2 Dimerization Mitigates the Infection by SARS-COV-2

The coronavirus disease 2019 (COVID-19) pandemic has caused over 6 million death and 460 million reported cases globally. More effective antiviral medications are needed to curb the continued spread of this disease. The infection by SARS-COV-2 virus is initiated via the interaction between the receptor binding domain (RBD) of the viral glycoprotein Spike (S protein) and the N-term peptidase domain (PD) of the angiotensin-converting enzyme 2 (ACE2) expressed on host cell membrane. ACE2 forms protein homodimer primarily through its ferredoxin-like fold domain (aka. Neck-domain). We investigated whether the dimerization of ACE2 receptor plays a role in SARS-COV-2 virus infection. We report here that the ACE2 receptor dimerization enhances the recognition of SARS-COV-2 S protein. A 43 amino acid peptide based on the N-term of Neck-domain could block the ACE2 dimerization and the interaction between RBD and ACE2, and mitigate the SARS-COV-2/host cell interaction. Our study illustrated a new route to develop potential therapeutics for the prevention and treatment of SARS-COV-2 viral infection.

molecular biology↗

bioRxiv2022

Comparative analysis about the structure of complete chloroplast genomes in genus Mangifera and accuracy verification about phylogenetic analysis based on gene ycf2 in genus level

Mango is an evergreen plant belonging to the genus Mangifera of the Anacardiaceae family. Genus Mangifera has 69 species of Mangifera around the world that are mainly distributed in tropical and subtropical countries, including India, Indonesia, the Malay Peninsula, Thailand, and South China. It is a popular tropical fruit known as the "King of Tropical Fruits". However, the study of the structure information of the complete chloroplast genome of Mangifera was microscopic, there was no report about the comparison of SSR, Ka/Ks, codons analysis and RNA editing, so in this study, we sequenced the 6 Mangifera samples and used three different ways to analyze the relationship of 6 species of Mangifera. Then we got some results, through the RNA editing and Ka/Ks calculating, we found the species could be divided into two groups, and the difference between the two groups was protein-coding gene ccsA. Moreover, all RNA editing occurred conversion of C to T and the gene ndhB had the most RNA editing sites in all species. In Ka/Ks analysis, the gene atpB, cemA, clpP, ndhD, petD, petB and ycf15 would be suffered from the positive selection after divergence. We also find the IR regions in these seven samples were very conservation through IR contraction and expansion and Sequence Divergence Analysis. Finally, we tried to confirm the relationship between 7 samples of Mangifera in Angiosperms in 3 different ways. Then we got that ML210 and MP090 had a closer relationship than others, MS796 had a closer relationship with ML210 and MP090 than others. At the same time, the method of phylogenetic analysis based on the gene ycf2 was not more accurate at the genus level than the method based on complete cp genome and proteincoding genes.

molecular biology↗

bioRxiv2022

Compartmental Neuropeptide Release Measured Using a New Oxytocin Sensor

As a peptide hormone and neuromodulator, oxytocin (OT) plays a critical role in a variety of physiological and pathophysiological processes in both the central nervous system and the periphery. However, the processes that regulate spatial OT release in the brain remain enigmatic. Here, we developed a genetically encoded GPCR activation-based (GRAB) OT sensor called GRABOT1.0. Using this sensor, we directly visualized stimulation-induced OT release from specific compartments of OT neurons in acute brain slices, and discovered that N-type calcium channels predominantly mediate axonal OT release, while L-type calcium channels mediate somatodendritic OT release. In addition, we found that components in the fusion machinery of OT release differ between axon terminals versus somata and dendrites. Finally, we demonstrated the sensor responses to the activation of OT neurons in various brain regions in vivo and revealed region specific OT release during male courtship behavior. Taken together, these results provide key insights regarding the role of compartmental OT release in the control of physiological and behavioral functions.

neuroscience↗

bioRxiv2022

Limb Specific Failure of Proliferation and Translation in the Mesenchyme Leads to Skeletal Defects in Diamond Blackfan Anemia

AbstractRibosomopathies are a class of disorders caused by defects in the structure or function of the ribosome and characterized by tissue-specific abnormalities. Diamond Blackfan anemia (DBA) arises from different mutations, predominantly in genes encoding ribosomal proteins (RPs). Apart from the anemia, skeletal defects are among the most common anomalies observed in patients with DBA, but they are virtually restricted to radial ray and other upper limb defects. What leads to these site-specific skeletal defects in DBA remains a mystery. Using a novel mouse model for RP haploinsufficiency, we observed specific, differential defects of the limbs. Using complementary in vitro and in vivo approaches, we demonstrate that reduced WNT signaling and subsequent increased {beta}-catenin degradation in concert with increased expression of p53 contribute to mesenchymal lineage failure. We observed differential defects in the proliferation and differentiation of mesenchymal stem cells (MSCs) from the forelimb versus the hind limbs of the RP haploinsufficient mice that persisted after birth and were partially rescued by allelic reduction of Trp53. These defects are associated with a global decrease in protein translation in RP haploinsufficient MSCs, with the effect more pronounced in cells isolated from the forelimbs. Together these results demonstrate translational differences inherent to the MSC, explaining the site-specific skeletal defects observed in DBA.

cell biology↗

bioRxiv2022

Chronic Ca2+ imaging of cortical neurons with long-term expression of GCaMP-X

Dynamic Ca2+ signals reflect acute changes in membrane excitability (e.g. sensory response), and also mediate intracellular signaling cascades normally of longer time scales (e.g., Ca2+-dependent neuritogenesis). In both cases, chronic Ca2+ imaging has been often desired, but largely hindered by unexpected cytotoxicity intrinsic to GCaMP, a popular series of genetically-encoded Ca2+ indicators. Here, we demonstrate that the recently developed GCaMP-X outperforms GCaMP in long-term probe expression and/or chronic Ca2+ imaging. GCaMP-X shows much improved compatibility with neurons and thus more reliable than GCaMP as demonstrated in vivo by acute Ca2+ responses to whisker deflection or spontaneous Ca2+ fluctuations over an extended time frame. Chronic Ca2+ imaging data ([≥]1 month) are acquired from the same set of cultured cortical neurons, unveiling that spontaneous/local Ca2+ activities would progressively develop into autonomous/global Ca2+ oscillations. Besides the morphological indices of neurite length or soma size, the major metrics of oscillatory Ca2+, including rate, amplitude, synchrony among different neurons or organelles have also been examined along with the developmental stages. Both neuritogenesis and Ca2+ signals are dysregulated by GCaMP in virus-infected or transgenic neurons, in direct contrast to GCaMP-X without any noticeable side-effect. Such in vitro data altogether consolidate the unique importance of oscillatory Ca2+ to activity-dependent neuritogenesis, as one major factor responsible for the distinctions between GCaMP vs GCaMP-X in vivo. For the first time with GCaMP-X of long-term expression in neurons, spontaneous and sensory-evoked Ca2+ activities are imaged and evaluated both in vitro and in vivo, providing new opportunities to monitor neural development or other chronic processes concurrently with Ca2+ dynamics.

neuroscience↗

bioRxiv2022

An integrated approach to protein discovery and detection from complex biofluids

Ovarian cancer, a leading cause of cancer related deaths among women, has been notoriously difficult to routinely screen for and diagnose early. Researchers and clinicians continue to seek routinely usable, non-invasive, screening methods as early detection significantly improves survival. Biomarker screening is ideal; however, currently available ovarian cancer biomarkers lack desirable sensitivity and specificity. Furthermore, the most fatal forms, high grade serous cancers often originate in the fallopian tube; therefore, sampling from the vaginal environment provides more proximal sources for tumor detection. To address these shortcomings and leverage proximal sampling, we developed an untargeted mass spectrometry microprotein profiling method and identified a signature of cystatin A, validated this protein in an animal model, and sought to overcome the limits of detection inherent to mass spectrometry by demonstrating that cystatin A is present at 100 pM concentrations using a label-free microtoroid resonator. The findings highlight the potential utility for early-stage detection where cystatin A levels would be low. Significance StatementIt is now clear that high-grade serous ovarian cancer can originate in the fallopian tube epithelium. These tumors colonize the ovary and then metastasize throughout the peritoneum. This discovery has raised important, and yet unaddressed, questions how we might be able to detect and screen for this deadly disease for which there is no routine screening. We have leveraged vaginal lavages from a murine model of the disease as a complex biological fluid for untargeted discovery of microproteins using mass. We improved our limits of detection by conjugating a cystatin A antibody to the surface of a microtoroid resonator to allow us to specifically detect cystatin A from vaginal lavages at early time points across biological replicates.

cancer biology↗

bioRxiv2022

Parasite defensive limb movements enhance signal attraction in male little torrent frogs: insight into the evolution of multimodal signals

Many animals rely on complex sexual signals that target multiple senses to attract mates and repel rivals. These multimodal mating displays can however also attract unintended receivers, which can be an important driver of signal complexity. Despite being taxonomically widespread, we often lack insight into how multimodal signals evolve from unimodal signals and in particular what roles unintended eavesdroppers play. Here we assess whether the physical movements of parasite defense behavior increase the complexity and attractiveness of an acoustic sexual signal in the little torrent frog (Amolops torrentis). Calling males of this species often display limb movements in order to defend against blood-sucking parasites such as frog-biting midges that eavesdrop on their acoustic signal. Through mate choice tests we show that some of these midge-evoked movements influence female preference for acoustic signals. Our data suggest that midge-induced movements may be incorporated into a sexual display, targeting both hearing and vision in the intended receiver. Females may play an important role in incorporating these multiple components because they prefer signals which combine multiple programs. Our results thus help to understand the relationship between ecological and sexual selection pressure operating on signalers and how in turn this may influence multimodal signal evolution.

evolutionary biology↗

bioRxiv2021

Opposing regulation of short-term memory by basal ganglia direct and indirect pathways that are coactive during behavior

The basal ganglia direct and indirect pathways are viewed to mediate opposing functions in movement. However, this classic model is challenged by recent findings that both pathways are coactive during behavior. We examined the roles of direct (dSPNs) and indirect (iSPNs) pathway spiny projection neurons in a decision-making task with a short-term memory (STM) component. Optogenetic stimulation of cortical-input-defined dSPNs and iSPNs during STM oppositely biased upcoming licking choice, without affecting licking execution. Optogenetically identified dSPNs and iSPNs showed similar response patterns, although with quantitative difference in spatiotemporal organization. To understand how coactive dSPNs and iSPNs play opposing roles, we recorded population activity in frontal cortex and the basal ganglia output nucleus SNr. Stimulation of dSPNs and iSPNs bidirectionally regulated cortical decision variable through the differential modulation of SNr ramping activity. These results reconcile different views by demonstrating that coactive dSPNs and iSPNs precisely shape cortical activity in a push-pull balance.

neuroscience↗