Biology subjects

Ye, Z.

Publications and source records attributed to Ye, Z..

At least 55 records · Page 3Linked to original sources

bioRxiv2025

STmiR: A Novel XGBoost-Based Framework for Spatially Resolved miRNA Activity Prediction

MicroRNAs (miRNAs) are critical regulators of gene expression in cancer biology; however, their spatial dynamics within tumor microenvironments (TME) remain underexplored owing to technical limitations in current spatial transcriptomics (ST) technologies. To address this gap, we present STmiR, a novel XGBoost-based framework for spatially resolved miRNA activity predictions. STmiR integrates bulk RNA-seq data (TCGA and CCLE) with spatial transcriptomics profiles to model nonlinear miRNA-mRNA interactions, achieving a high predictive accuracy (Spearmans {rho} > 0.8) across four major cancer types (breast, lung, ovarian, and prostate). Applied to 10X Visium ST datasets from nine cancers, STmiR identified six pan-cancer conserved miRNAs (e.g., hsa-miR-21, hsa-let-7a) consistently ranked in the top 40 across malignancies, and uncovered cell-type-specific regulatory networks in fibroblasts, B cells, and malignant cells. A breast cancer case study validated the utility of STmiR by linking miR-205 to androgen receptor (AR) signaling and miR-200b to epithelial-mesenchymal transition (EMT). By enabling the spatial mapping of miRNA activity, STmiR provides a transformative tool to dissect miRNA-mediated regulatory mechanisms in cancer progression and TME remodeling, with implications for biomarker discovery and precision oncology. HighlightsO_LIFirst integration of XGBoost and spatial transcriptomics: STmiR pioneers a machine learning framework to predict miRNA activity in spatially heterogeneous tissues, overcoming limitations of linear correlation-based methods. C_LIO_LIHigh accuracy and generalizability: Demonstrates robust performance (Spearmans {rho} > 0.8) across four cancer types validated by independent datasets. C_LIO_LIPan-cancer conserved miRNAs: Six miRNAs (e.g., hsa-miR-21 and hsa-let-7a) were shared across nine cancers, implicating their roles in core oncogenic pathways. C_LI Key ContributionsO_LIMethodological innovation: Combines XGBoosts nonlinear modeling with spatial transcriptomics to resolve miRNA activity in multicellular contexts. C_LIO_LIBiological discovery: Uncovers the conserved and context-dependent roles of miRNAs in tumor progression and microenvironment crosstalk. C_LIO_LITranslational impact: Provides a computational platform for identifying spatially regulated therapeutic targets in cancer. C_LI

bioinformatics↗

bioRxiv2025

Sky islands of Southwest China. II: Unraveling hidden species diversity of talpid moles using phylogenomics and skull-based deep learning

The sky islands of Southwest China, characterized by dramatic topographical and climatic variations, are prominent hotspots of biodiversity and endemism. Organisms inhabiting middle-to-high elevation habitats in this region are geographically isolated within distinct mountain chains, which over geological time have been subjected to isolation-by-distance and isolation-by-environment. These processes have led to profound allopatric diversification and strong phylogeographic structuring, resulting in a plethora of genetically distinct cryptic species, as is becoming increasingly evident for many small mammal families. However, morphological conservatism can pose significant challenges in delineating these clades within species complexes. In this study, we leverage artificial intelligence technologies to unravel the hidden species diversity of moles (family Talpidae) in Southwest Chinas sky islands. We first employed ultraconserved elements (UCEs) to investigate the evolutionary history of talpid moles, conducted molecular species delimitation using mitochondrial and multi-locus genes, and utilized both traditional and geometric morphometrics to examine their morphological disparity. To address the challenges of morphology based cryptic species identification, we developed a deep learning Hierarchical Identification of Species NETwork (HIS-NET) to create an image-based model that analyzes four different views of the skull/mandible to distinguish genera and species hierarchically. HIS-NET not only achieved expert-level accuracy in species identification but also effectively distinguished between cryptic and known species, aiding in the identification of key morphological variation intervals. Our results support the recognition of allopatrically distributed taxa in Euroscaptor and Parascaptor as full species, thereby confirming that species diversity in this region remains underestimated. Beyond advancing our understanding of speciation in this unique and fragile ecosystem, our study serves as a proof-of-concept, demonstrating the power of deep learning in unraveling hidden biodiversity within this and other species complexes.

zoology↗

bioRxiv2025

Neuropixels Opto: Combining high-resolution electrophysiology and optogenetics

High-resolution extracellular electrophysiology is the gold standard for recording spikes from distributed neural populations, and is especially powerful when combined with optogenetics for manipulation of specific cell types with high temporal resolution. We integrated these approaches into prototype Neuropixels Opto probes, which combine electronic and photonic circuits. These devices pack 960 electrical recording sites and two sets of 14 light emitters onto a 70 m wide, 1 cm long shank, allowing spatially addressable optogenetic stimulation with blue and red light. In mouse cortex, Neuropixels Opto probes delivered high-quality recordings together with spatially addressable optogenetics, differentially activating or silencing neurons at distinct cortical depths. In mouse striatum and other deep structures, Neuropixels Opto probes delivered efficient optotagging, facilitating the identification of two cell types in parallel. Neuropixels Opto probes represent an unprecedented tool for recording, identifying, and manipulating neuronal populations.

neuroscience↗

bioRxiv2025

CRISPR/Cas9-mediated germline mutagenesis in the subsocial parasitoid wasp, Sclerodermus guani

The ectoparasitoid wasp Sclerodermus guani (Hymenoptera: Bethylidae), as a subsocial insect, is widely applied in biological control against beetle vectors of pine wood nematodes. Despite significant advances in behavioral research, functional genetics in S. guani remains underdeveloped due to the absence of efficient gene manipulation tools. In this study, we employed CRISPR-mediated mutagenesis to achieve germline gene knockout targeting the eye pigment associated gene kynurenine 3-monooxygenase (KMO). Phylogenetic analysis revealed that S. guani KMO shares a close relationship with its homolog in Prorops nasuta (Hymenoptera: Bethylidae). Two single-guide RNAs (sgRNAs), coupled with Cas9 protein with and without nuclear localization signal (NLS) were tested. Both sgRNAs induced specific in vitro DNA cleavage and in vivo heritable indels at the target genomic loci. Homozygous null mutant females and males exhibit a white-eye phenotype, which was identified during pupal stage. Optimal editing efficiency in vivo was achieved using the Cas9-NLS variant. Given the complication of germline gene editing in eusocial Hymenopterans, the application of CRISPR in the subsocial parasitoid wasp S. guani provides an accessible research platform for the molecular evolution of insect sociality.

molecular biology↗

bioRxiv2024

Inhibition of β-catenin signaling by Amyloid-β in endothelial cells impairs vascular barrier integrity

Dysfunction of the blood-brain barrier (BBB) is emerging as a critical mediator of Alzheimers Disease (AD) progression and precedes the formation of large Amyloid-{beta} (A{beta}) plaques in AD patients. Maintenance of the blood brain barrier integrity by brain microvascular endothelial cells (BMECs) is essential for brain homeostasis and is in part maintained by WNT/{beta}-catenin signaling. We hypothesized that A{beta} induces blood-brain barrier dysfunction by inhibiting WNT/{beta}- catenin signaling in brain endothelial cells, leading to reduced expression of BBB-related genes and barrier function. In brain endothelial cells, we found that A{beta} directly decreased {beta}-catenin transcriptional activity, but also inhibited activation of {beta}-catenin by the WNT3A peptide. Additionally, A{beta} reduced barrier integrity of ECs, which was in part restored by exposure to exogenous WNT3A. We observed A{beta}-induced inhibition within 3 hours of exposure. A{beta}-induced inhibition of {beta}-catenin signaling was consistent across both immortalized brain ECs and ECs differentiated from human induced pluripotent stem cells(iPSCs). We next investigated human iPSCs with and without the N141I mutation in presenilin-2 (PSEN2), known to increase A{beta} buildup and familial AD risk. We found the AD ECs showed smaller cell size and expressed lower VE-cadherin at the protein level. RNA sequencing revealed that the presence of PSEN2 N141I did not significantly impact gene expression of genes coding for proteins canonically involved in barrier integrity but did show differences in the expression of transposable elements. These results indicate that BBB dysfunction early in AD may be the result of A{beta} in the brain impairing WNT/{beta}-catenin signaling which maintains the barrier integrity of brain endothelial cells.

neuroscience↗

bioRxiv2024

Simultaneous mesoscopic measurement and manipulation of mouse cortical activity

Dynamics of activity across the cerebral cortex at the mesoscopic scale -- coordinated fluctuations of local populations of neurons -- are essential to perception and cognition and relevant to computations like sensorimotor integration and goal-directed task engagement. However, understanding direct causal links between population dynamics and behavior requires the ability to manipulate mesoscale activity and observe the effect of manipulation across multiple brain regions simultaneously. Here, we develop a novel system enabling simultaneous recording and manipulation of activity across the dorsal cortex of awake mice, compatible with large-scale electrophysiology from any region across the brain. Transgenic mice expressing the GCaMP calcium sensor are injected systemically with an adeno-associated virus driving expression of the ChrimsonR excitatory opsin. This strategy drives expression of the blue-excited calcium indicator, GCaMP, in excitatory neurons and red-excited Chrimson opsin in inhibitory neurons. We demonstrate widefield single-photon calcium imaging and simultaneous galvo-targeted laser stimulation over the entire dorsal cortical surface. The light channels of the imaging and the opsin do not interfere. We characterize the spatial and temporal resolution of the method, which is suitable for targeting specific cortical regions and specific time windows in behavioral tasks. The preparation is stable over many months and thus well-suited for long-term behavioral experiments. This technique allows for studying the effect of cortical perturbations on cortex-wide activity, on subcortical spiking activity, and on behavior, and for designing systems to control cortical activity in closed-loop.

neuroscience↗

bioRxiv2024

Speed modulations in grid cell information geometry

Grid cells, known for their hexagonal spatial firing patterns, are widely regarded as essential to the brains internal representation of the external space. Maintaining an accurate internal spatial representation is challenging when an animal is running at high speeds, as its self-location constantly changes. Previous studies of speed modulation of grid cells focused on individual or pairs of grid cells, yet neurons represent information via collective population activity. Population noise covariance can have significant impact on information coding that is impossible to infer from individual neuron analysis. To address this issue, we developed a novel Gaussian Process with Kernel Regression (GKR) method that allows study the simultaneously recorded neural population representation from an information geometry framework. We applied GKR to grid cell population activity, and found that running speed increases both grid cell activity toroidal-like manifold size and noise strength. Importantly, the effect of manifold dilation outpaces the effect of noise increasement, as indicated by the overall higher Fisher information at increasing speeds. This result is further supported by improved spatial information decoding accuracy at high speeds. Finally, we showed that the existence of noise covariance is information detrimental because it causes more noise projected onto the manifold surface. In total, our results indicate that grid cell spatial coding improves with increasing running speed. GKR provides a useful tool to understand neural population coding from an intuitive information geometric perspective.

neuroscience↗

bioRxiv2024

Brain-like border ownership signals support prediction of natural videos

To make sense of visual scenes, the brain must segment foreground from background. This is thought to be facilitated by neurons in the primate visual system that encode border ownership (BOS), i.e. whether a local border is part of an object on one or the other side of the border. It is unclear how these signals emerge in neural networks without a teaching signal of what is foreground and background. In this study, we investigated whether BOS signals exist in PredNet, a self-supervised artificial neural network trained to predict the next image frame of natural video sequences. We found that a significant number of units in PredNet are selective for BOS. Moreover these units share several other properties with the BOS neurons in the brain, including robustness to scene variations that constitute common object transformations in natural videos, and hysteresis of BOS signals. Finally, we performed ablation experiments and found that BOS units contribute more to prediction than non-BOS units for videos with moving objects. Our findings indicate that BOS units are especially useful to predict future input in natural videos, even when networks are not required to segment foreground from background. This suggests that BOS neurons in the brain might be the result of evolutionary or developmental pressure to predict future input in natural, complex dynamic visual environments.

neuroscience↗

bioRxiv2024

Temporal asymmetry of neural representations predicts memory decisions

A stimulus can be familiar for multiple reasons. It might have been recently encountered, or is similar to recent experience, or is similar to typical experience. Understanding how the brain translates these sources of similarity into memory decisions is a fundamental, but challenging goal. Here, using fMRI, we computed neural similarity between a current stimulus and events from different temporal windows in the past and future (from seconds to days). We show that trial-by-trial memory decisions (is this stimulus old?) were predicted by the difference in similarity to past vs. future events (temporal asymmetry). This relationship was (i) evident in lateral parietal and occipitotemporal cortices, (ii) strongest when considering events from the recent past (minutes ago), and (iii) most pronounced when veridical (true) memories were weak. These findings suggest a new perspective in which the brain supports memory decisions by comparing what actually occurred to what is likely to occur.

neuroscience↗

bioRxiv2024

Tailoring the self-blinking of sulfonamide rhodamine for long-term protein-localizing super-resolution imaging

Life continually changes its protein arrangements, yet the molecular ultradetails are covered by the short-lived deficiency of fluorophore blinking for super-resolution imaging. Herein, we proposed a crowding strategy to conserve the self-blinking events for prolonging the imaging time. We engineered sulfonamide rhodamines through atom-radii expansion (O-C-Si), rationally reversing xanthene intersection and creating stacking to enhance ring-opening energetical barriers. Our stacked rhodamines demonstrated decreased recruiting rates and extended survival lifetimes at single-molecule level, validating the decreased self-blinking kinetics from stacking strategy. Accordingly, our silicon-substituted rhodamine enabled persistent molecular localization imaging of various sub-organelle proteins to state-of-art time (0.5 h) in living cells, with versatile capabilities for three-dimensional and dual-color imaging. We envision our crowding strategy sets a new stage for prolongating super-resolution imaging through structural engineering.

biochemistry↗

bioRxiv2024

Global analysis of protein turnover dynamics in single cells

Even with recent improvements in sample preparation and instrumentation, single-cell proteomics (SCP) analyses mostly measure protein abundances, making the field unidimensional. In this study, we employ a pulsed stable isotope labeling by amino acids in cell culture (SILAC) approach to simultaneously evaluate protein abundance and turnover in single cells (SC-pSILAC). Using state-of-the-art SCP workflow, we demonstrated that two SILAC labels are detectable from [~]4000 proteins in single HeLa cells recapitulating known biology. We investigated drug effects on global and specific protein turnover in single cells and performed a large-scale time-series SC-pSILAC analysis of undirected differentiation of human induced pluripotent stem cells (iPSC) encompassing six sampling times over two months and analyzed >1000 cells. Abundance measurements highlighted cell-specific markers of stem cells and various organ-specific cell types. Protein turnover dynamics highlighted differentiation-specific co-regulation of core members of protein complexes with core histone turnover discriminating dividing and non-dividing cells with potential in stem cell and cancer research. Our study represents the most comprehensive SCP analysis to date, offering new insights into cellular diversity and pioneering functional measurements beyond protein abundance. This method distinguishes SCP from other single-cell omics approaches and enhances its scientific relevance in biological research in a multidimensional manner.

systems biology↗

bioRxiv2024

The Folding of Germ Granule mRNAs Controls Intermolecular Base Pairing in Germ Granules and Maintains Normal Fly Development

Drosophila germ granules enrich mRNAs critical for fly development. Within germ granules, mRNAs form multi-transcript clusters marked by increased mRNA concentration, creating an elevated potential for intermolecular base pairing. However, the type and abundance of intermolecular base pairing in mRNA clusters is poorly characterized. Using single-molecule super-resolution microscopy, chemical probing for base accessibility, phase separation assays, and simulations, we demonstrated that mRNAs remain well-folded upon localization to germ granules. While most base pairing is intramolecular, mRNAs still display the ability for intermolecular base pairing, facilitating clustering without high sequence complementarity or significant melting of secondary structure. This base pairing among mRNAs is driven by scattered and discontinuous stretches of bases appearing on the surface of folded RNAs, providing multivalency to clustering but exhibits low probability for sustained interactions. Notably, engineered germ granule mRNAs with exposed GC-rich complementary sequences (CSs) presented within stable stem loops induce sustained base pairing in vitro and enhanced intermolecular interactions in vivo. However, the presence of these stem loops alone disrupts fly development, and the addition of GC-rich CSs exacerbates this phenotype. Although germ granule mRNAs contain numerous GC-rich CSs capable of stable intermolecular base pairing, they are primarily embedded by RNA folding. This study emphasizes the role of RNA folding in controlling the type and abundance of intermolecular base pairing, thereby preserving the functional integrity of mRNAs within the germ granules.

molecular biology↗

bioRxiv2024

Brain-wide functional connectome analysis of 40,000 individuals reveals brain networks that show aging effects in older adults

The functional connectome changes with aging. We systematically evaluated aging related alterations in the functional connectome using a whole-brain connectome network analysis in 39,675 participants in UK Biobank project. We used adaptive dense network discovery tools to identify networks directly associated with aging from resting-state fMRI data. We replicated our findings in 499 participants from the Lifespan Human Connectome Project in Aging study. The results consistently revealed two motor-related subnetworks (both permutation test p-values <0.001) that showed a decline in resting-state functional connectivity (rsFC) with increasing age. The first network primarily comprises sensorimotor and dorsal/ventral attention regions from precentral gyrus, postcentral gyrus, superior temporal gyrus, and insular gyrus, while the second network is exclusively composed of basal ganglia regions, namely the caudate, putamen, and globus pallidus. Path analysis indicates that white matter fractional anisotropy mediates 19.6% (p<0.001, 95% CI [7.6% 36.0%]) and 11.5% (p<0.001, 95% CI [6.3% 17.0%]) of the age-related decrease in both networks, respectively. The total volume of white matter hyperintensity mediates 32.1% (p<0.001, 95% CI [16.8% 53.0%]) of the aging-related effect on rsFC in the first subnetwork.

neuroscience↗

bioRxiv2024

Structural insights into transcription regulation of the global virulence factor PhoP from Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb), remaining as the leading cause of the worldwide threat Tuberculosis, relies heavily on its transcriptional reprogramming of diverse stress genes to swiftly adapt to adverse environments and ensure infections. The global virulence factor PhoP plays a pivotal role in coordinating transcription activation or repression of the essential phosphate-nitrogen metabolic remodeling genes. However, what defines PhoP to deferentially act as an activator or a repressor remains largely unexplored. Here, we determine one cryo-EM structure of Mtb RNAP-promoter open complex, three cryo-EM structures of PhoP-dependent transcription activation complexes (PhoP-TACs) consisting of Mtb RNA polymerase (RNAP), different number of PhoP molecules binding to different types of well-characterized consensus promoters, and one cryo-EM structure of Mtb PhoP-dependent transcription repression complex (PhoP-TRC) comprising of Mtb RNAP, PhoP, the nitrogen metabolism regulator GlnR and their co-regulated promoter. Structural comparisons reveal phosphorylation of PhoP is required for stabilization of PhoP-TACs, PhoP specifically recognizes promoters as novel tandem dimers and recruits RNAP through extensively interacting with its conserved {beta} flap and {sigma}AR4 domains. Strikingly, the distinct promoter spacer length and PhoP-GlnR interactions in PhoP-TRC constrain the upstream DNA into a distinct topology and retain PhoP in a novel dragging repression mode. Collectively, these data highlight the dual regulatory mechanisms of PhoP-dependent transcription regulation in governing stress adaptation. These findings provide structural basis for developing potential anti-tuberculosis drugs and/or interventions.

microbiology↗

bioRxiv2024

Persistent lung inflammation and alveolar-bronchiolization due to Notch signaling dysregulation in SARS-CoV-2 infected hamster

Long COVID or Post-acute sequalae of COVID-19 (PASC) defines the persistent signs, symptoms, and conditions long after initial SARS-CoV-2 infection which affecting over 10% of COVID-19 patients, with 40% of them affecting respiratory system. The lung histopathological changes and underlying mechanism remain elusive. Here we systemically investigate histopathological and transcriptional changes at 7, 14, 42, 84 and 120 days-post-SARS-CoV-2-infection (dpi) in hamster. We demonstrate persistent viral residues, chronic inflammatory and fibrotic changes from 42dpi to 120dpi. The most prominent lung histopathological lesion is multifocal alveolar-bronchiolization observed in every animal from 14dpi until 120dpi. However, none of the above are observed in hamsters recovered from influenza A infection. We show airway progenitor CK14+ basal cells actively proliferate, differentiate into SCGB1A+ club cell or Tubulin+ ciliated cells, leading to alveolar-bronchiolization. Most importantly, Notch pathway is persistently upregulated. Intensive Notch3 and Hes1 protein expression are detected in alveolar-bronchiolization foci, suggesting the association of sustained Notch signaling with dysregulated lung regeneration. Lung spatial transcriptomics show upregulation of genes positively regulating Notch signaling is spatially overlapping with alveolar-bronchiolization region. To be noted, significant upregulation of tumor-related genes was detected in abnormal bronchiolization region by spatial transcriptomics analysis, indicating possible risk of lung carcinoma. Collectively, our data suggests SARS-CoV-2 infection caused chronic inflammatory and fibrotic tissue damages in hamster lung, sustained upregulation of Notch pathway signaling contributed to the dysregulated lung regeneration and CK14+ basal cells-driven alveolar-bronchiolization. The study provides important information for potential therapeutic approaches and probable long-term surveillance of malignancy in PASC management.

microbiology↗

bioRxiv2024

Molecular stratification of human fetal vaginal epithelium by spatial transcriptome analysis

The human vaginal epithelium is a crucial component in numerous reproductive processes and serves as a vital protective barrier against pathogenic invasion. Despite its significance, a comprehensive exploration of its molecular profiles, including molecule expression and distribution across its multiple layers, remains elusive. In our study, we undertook a spatial transcriptomic analysis within the vaginal wall of human fetuses to fill this knowledge gap. We successfully categorized vaginal epithelium into four distinct zones based on their transcriptomic profiles and anatomical features. This approach unveiled unique transcriptomic signatures within these regions, allowing us to identify differentially expressed genes and uncover novel markers for distinct regions of the vaginal epithelium. Additionally, our findings have highlighted the varied expression of KRT genes across different zone of the vaginal epithelium, with a gradual shift in expression patterns observed from the basal layer to the surface/superficial layer. This suggests a potential differentiation trajectory of human vaginal epithelium, shedding light on the dynamic nature of this tissue. Furthermore, abundant biological processes were found to be enriched in the basal zone by the KEGG pathway analysis, indicating an active state of the basal zone cells. Subsequently, the expression of latent stem cell markers in the basal zone were identified. In summary, our research provides crucial understanding of human vaginal epithelial cells and the complex mechanisms of the vaginal mucosa, with potential applications in vaginal reconstruction and drug delivery, making this atlas a valuable tool for future research in womens health and reproductive medicine.

cell biology↗

bioRxiv2024

Photo-Uncaging Triggers on Self-Blinking to Control Single-Molecule Fluorescence Kinetics for Super-Resolution Imaging

Super-resolution imaging in a single-molecule localization approach has transformed the bulk fluorescence requirements to a single-molecule level, raising a revolution in the fluorophore engineering. Yet, it is a challenge to structurally devise fluorophores manipulating the single-molecule blinking kinetics. In this pursuit, we have developed a new strategy by innovatively integrating the photoactivatable nitroso-caging strategy into self-blinking sulfonamide, to forming a nitroso-caged sulfonamide rhodamine (NOSR). Our fluorophore demonstrated controllable self-blinking events upon photo-triggered uncaging release. This exceptional blink kinetics improved integrity in super-resolution imaging microtubules compared to self-blinking analogues. With the aid of paramount single-molecule fluorescence kinetics, we successfully reconstructed the axial morphology of mitochondrial outer membranes. We foresee that our synthetic approach of photoactivation and self-blinking would set a new avenue for devising rhodamines for super-resolution imaging. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/580074v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@18d51d5org.highwire.dtl.DTLVardef@f7a1cdorg.highwire.dtl.DTLVardef@19fcc7dorg.highwire.dtl.DTLVardef@2a5bcb_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2024

The type of inhibition provided by thalamic interneurons alters the input selectivity of thalamocortical neurons.

A fundamental problem in neuroscience is how neurons select for their many inputs. A common assumption is that a neurons selectivity is largely explained by differences in excitatory synaptic input weightings. Here we describe another solution to this important problem. We show that within the first order visual thalamus, the type of inhibition provided by thalamic interneurons has the potential to alter the input selectivity of thalamocortical neurons. To do this, we developed conductance injection protocols to compare how different types of synchronous and asynchronous GABA release influence thalamocortical excitability in response to realistic patterns of retinal ganglion cell input. We show that the asynchronous GABA release associated with tonic inhibition is particularly efficient at maintaining information content, ensuring that thalamocortical neurons can distinguish between their inputs. We propose a model where alterations in GABA release properties results in rapid changes in input selectivity without requiring structural changes in the network.

neuroscience↗