Biology subjects

Feng, G.

Publications and source records attributed to Feng, G..

At least 19 recordsLinked to original sources

bioRxiv2026

From micro-architecture to networks: canonical neurobiological architecture of functional brain organization across the lifespan and in psychopathology

Understanding how macroscale functional network connectivity (FNC) across the lifespan and in psychopathology is spatially organized with respect to microscale neurobiological architecture remains a challenge. Here, we constructed a cross-omics mapping framework by linking resting-state fMRI data (5,349 individuals, 6-80 years) with 49 neurobiological markers (24 cell types, 19 neurotransmitters, 6 mitochondria). We show that FNC development and aging unfold along cellular and molecular gradients. Specifically, spatial correspondence between age-related FNC changes and neurobiological microprofile networks varied by life stage, peaking for cell types in adolescence, neurotransmitter systems in mid-young adulthood and mitochondrial phenotypes in early adulthood. Applying normative modeling to 5 psychiatric disorders (schizophrenia, bipolar disorder, major depressive disorder, autism, and attention-deficit/hyperactivity disorder), we identified disorder-specific and cross-disorder FNC phenotypes spatially associated with neurobiological architecture. Together, these findings provide a hypothesis-generating framework linking functional brain organization and dysfunction to canonical neurobiological architecture across the lifespan and psychiatric disorders.

neuroscience↗

bioRxiv2026

Human brain white matter charts in international populations

Brain charts provide normative references for identifying neurodevelopmental milestones and clinically meaningful deviations. Existing white matter (WM) charts are derived predominantly from European and North American populations, limiting generalizability. Here, we established the first set of population-specific WM charts of 198 morphological and microstructural phenotypes for both Chinese (N=19,215) and Western (N=15,584) populations across the human lifespan. Developmental trajectories and spatial organization of WM maturation and degeneration were broadly conserved across the populations, whereas maturational timing varied across pathways and metrics. The Chinese population showed earlier maturation in several projection and sensorimotor pathways, but more protracted maturation in higher-order association and limbic pathways. Chinese population-matched charts more accurately predicted WM phenotypes and detected more extreme disease-related deviations in brain health in the Chinese population than Western-derived models. Individual deviation patterns further discriminated patients from healthy controls and predicted cognitive performance and plasma biomarkers. Our findings reveal population-specific WM maturation and show that reference-population mismatch can reduce the accuracy and clinical sensitivity of normative brain charts.

neuroscience↗

bioRxiv2026

Baseline growth rate shapes pollutant impacts in aquatic environments: Evidence from antibiotic responses in the harmful cyanobacterium Microcystis

Hormesis is an important consideration in chemical risk assessment across most aquatic environments. Evidence suggests that hormetic responses are shaped by organismal physiological processes. Accordingly, predictions of hormesis under environmentally realistic conditions should account for physiological traits. Yet the role of these traits remains largely unexplored. This study investigated how baseline growth rate modulates antibiotic responses in the harmful cyanobacterium Microcystis and the underlying mechanisms. Results showed that at an antibiotic concentration of 200 ng L-1 (representing environmental concentration levels), slow-growing Microcystis populations exhibited an obvious growth enhancement more than 4-fold greater than that of fast-growing populations, and this enhancement was positively correlated with cellular reserves. A baseline growth rate below 0.19 day-1 emerged as the threshold below which hormetic responses were consistently observed. This study provides pioneering insights into how organisms' physiological states influence pollutant-induced hormetic responses in aquatic environments. Our findings point to a central principle for extrapolation that laboratory-derived toxicological responses may not translate directly to the field unless key physiological traits of the organisms are explicitly considered. In this regard, baseline growth rate and energy reserves may be key physiological traits for reliably predicting toxic effects at the population level. This study also makes an initial attempt to conceptualize a physiology-anchored framework for strengthening risk assessment of low-level emerging contaminants.

ecology↗

bioRxiv2026

Telomerase RNA regulates the epigenome primed for human lineage commitment

Telomerase RNA (TERC) is known as the essential template for telomere elongation. Here, we report an unexpected role for TERC in regulating chromatin accessibility, which is primed for determining the cell fate of human embryonic stem cells (hESCs). TERC-deficient hESCs retain critical markers for pluripotency but fail to undergo lineage differentiation as shown by standard in vivo teratoma formation as well as in vitro differentiation assays, which is consistent with repressed transcription during differentiation into the three germ lineages. Notably, transient re-introduction of TERC into TERC-deficient hESCs rescued lineage differentiation capacity without restoring telomere length. TERC binds to the promoters and enhancers of developmental genes marked by H3K27ac to maintain an open chromatin state. Loss of TERC reduces H3K27ac deposition and decreases chromatin accessibility through the remodelling of three-dimensional genome organization, including TAD boundary insulation and compartment switching. Collectively, our findings reveal that TERC is a chromatin-associated noncoding RNA that regulates the epigenomic architecture that governs cell fate for lineage commitment during development.

cell biology↗

bioRxiv2026

Cerebellar microRNA-206 tunes Purkinje neuron firing dynamics to control sensorimotor gating

MicroRNAs are potent regulators of gene expression in the brain, yet the cellular mechanisms through which they shape neuronal activity and behavior remain poorly understood. MicroRNA-206 (miR-206) has been genetically and transcriptionally linked to schizophrenia and other neuropsychiatric disorders, but its functions in the nervous system are largely unknown. Here we show that miR-206 expression in the brain is restricted to postnatal cerebellar Purkinje cells (PCs). miR-206 was dispensable for PC cell fate specification, dendritic morphogenesis, and cerebellar-regulated motor coordination. Transcriptional profiling with single-nucleus and spatial resolution, integrated with Ago2-associated miRNA-target repression mapping (HITS-CLIP) and ribosome-associated RNA profiling (TRAP-seq), showed that miR-206 regulates translational programs in PCs controlling neuronal excitability. Accordingly, miR-206 deficiency increased the tonic firing of PCs, whereas elevating miR-206 expression shifted PCs from tonic to high-frequency burst firing. Constitutive or PC-specific deletion of miR-206 impaired prepulse inhibition (PPI) of the acoustic startle response, a conserved form of sensorimotor gating disrupted in schizophrenia and related disorders. Restoration of miR-206 expression in PCs rescued PPI deficits in miR-206-deficient mice, while elevating miR-206 expression in PCs impaired PPI in wild-type animals. Together, these findings reveal that a schizophrenia-linked microRNA tunes Purkinje neuron firing dynamics to control sensorimotor gating.

neuroscience↗

bioRxiv2026

Combined Checkpoint Inhibition Amplifies Post-Infarction Injury via T Cell-Mediated Macrophage Activation

BackgroundThis study aimed to investigate whether combined PD-1/CTLA-4 immune checkpoint inhibition predisposes the heart to a hyperinflammatory state, thereby exacerbating cardiac injury following acute myocardial infarction (MI), a critical unresolved question in cardio-oncology. MethodsMyocardial infarction was induced in Pd1-/-Ctla4+/- mice, a genetic model mimicking combined checkpoint inhibition. Key mechanistic insights were gained through in vivodepletion of CD8+ T cells (using anti-CD8a antibody) and pharmacological inhibition of the JAK-STAT1 pathway (using Tofacitinib). Cardiac function, structural injury, and immune responses were comprehensively assessed via echocardiography, flow cytometry, immunofluorescence, and molecular analyses. ResultsCompared to wild-type controls, Pd1-/-Ctla4+/- mice exhibited significantly increased post-MI mortality, worse cardiac function, and larger infarct size. Mechanistically, the aggravated injury was driven by an amplified infiltration of activated, IFN-{gamma}-producing CD8+ T cells, which activated the JAK-STAT1 pathway in macrophages, polarizing them towards a pro-inflammatory state. Depleting CD8+ T cells or inhibiting the JAK-STAT1 pathway effectively attenuated macrophage-driven inflammation and improved all aspects of post-MI injury. ConclusionsCombined PD-1/CTLA-4 blockade exacerbates post-infarction cardiac injury by promoting CD8+ T cell-mediated activation of macrophages via the JAK-STAT1 axis. This work elucidates MI as a context-dependent immune-related adverse event in ICI therapy and identifies CD8+ T cells and the JAK-STAT1 pathway as promising therapeutic targets for cardioprotection in these patients. RESEARCH PERSPECTIVEO_ST_ABSWhat Is New?C_ST_ABSO_LIThis study identifies acute myocardial infarction (MI) as a potential, context-dependent immune-related adverse event in the setting of combined PD-1/CTLA-4 checkpoint inhibition, shifting the paradigm beyond the classic focus on myocarditis. C_LIO_LIIt elucidates a novel pathogenic axis where combined checkpoint deficiency exacerbates post-MI injury specifically through CD8+ T cell-derived IFN-{gamma}, which activates macrophages via the JAK-STAT1 pathway. C_LI What Question Should Be Addressed Next?O_LIFuture studies should employ anti-PD-1/CTLA-4 monoclonal antibodies in wild-type or humanized mouse models to validate findings and better recapitulate the pharmacokinetics of clinical ICI therapy, strengthening translational relevance. C_LIO_LIThe long-term consequences of this primed inflammatory state on chronic cardiac remodeling, heart failure development, and the potential interplay with atherosclerosis warrant further investigation. C_LI

immunology↗

bioRxiv2026

Computational aberration-corrected volumetric imaging of single retinal cells in the living eye

The eye offers a unique non-invasive window for accessing single-cell level structures and functions of the central nervous system (CNS) throughout the retina. However, strong and space-varying ocular aberrations, along with limited volume rates, challenge large-scale cellular imaging in living eyes and stymie the full potential of possible biological and pathological studies in retina. Here, we present plenoptic illumination scanning laser ophthalmoscopy (PI-SLO), a 3D fluorescent retinal imaging modality that enables high-speed, widefield, volumetric single-cell imaging with low phototoxicity. By capturing multiple angular images of fluorescence signals from the entire volume, PI-SLO enables digital aberration correction and 3D imaging across a >20{o} FOV with >23 Hz volume rate. We leverage this structural and functional imaging modality to investigate three key aspects of CNS physiology through the living mouse retina, including: microglial process dynamics, vascular perfusion, and light evoked calcium fluxes in inner retinal neurons. PI-SLO is a versatile non-invasive platform for in vivo investigation of retinal and CNS physiology at the cellular level.

bioengineering↗

bioRxiv2026

An Asynchronous Production Line of Meiotic Prophase I in the Mouse Fetal Ovary

The initiation of meiosis in the mammalian female germline has long been described as a synchronous event, occurring within a narrow developmental window. Here, we challenge this paradigm through a systematic, quantitative analysis of meiotic entry and progression in the mouse fetal ovary. Using dynamic expression profiling of key regulators Stra8, Sycp1, and Sycp3 alongside proliferation markers, we demonstrate that germ cells enter meiosis asynchronously and continuously between embryonic days E12.5 and E16.5. During this extended period, mitotic proliferation persists, indicating that germ cells are progressively recruited into the meiotic pathway rather than halting division simultaneously. Homologous chromosome synapsis, marked by Sycp1/Sycp3 co-localization, initiates at E14.5 and is completed prenatally by E18.5. Integrating these data into a continuous-time Markov chain model, we derive a "meiotic clock" that predicts fixed temporal intervals from meiotic entry to synapsis completion ([~]72 hours) and to meiotic arrest ([~]91 hours), regardless of entry time. This model provides a predictive framework for germ cell development and establishes that female meiotic initiation is a prolonged, asynchronous production line rather than a synchronized transition, reshaping our understanding of oogenesis and its regulatory logic. TEASERThe initiation of female meiosis in mice is redefined as an asynchronous, continuous production line from E12.5 to E16.5, supported by a predictive "meiotic clock" model with fixed temporal intervals for synapsis and arrest.

developmental biology↗

bioRxiv2025

Genomic Structural Variation Underlies Cell-Type-Specific Betacyanin Variegation in Chenopodium quinoa

The allotetraploid crop quinoa (Chenopodium quinoa) accumulates red/violet betacyanins, which function as vital stress-mitigating antioxidants. We investigated the genetic basis of red/green variegation observed in the aerial organs of the P0429 accession. We demonstrated that this color mosaic is primarily localized to the epidermal bladder cells (EBCs), with red EBCs accumulating [~]50-fold higher betacyanin levels than colorless EBCs. Cell-type-specific RNA-sequencing of EBCs identified the cytochrome P450 gene Cqu0091301 (CYP76AD) as the dominant and rate-limiting factor, exhibiting strong upregulation in red EBCs. This high pigmentation requires a specific structural variation in the P0429 accession: a [~]4-kb genomic insertion that restores the full functionality of Cqu0091301, which is otherwise truncated and non-functional in common reference genomes. Genomic analysis reveals that Cqu0091301 is part of a CYP76AD-DODA gene cluster. Notably, expression analysis revealed functional divergence between the quinoa subgenomes, with B-subgenome CYP76AD genes highly dominant in EBCs, while A-subgenome homologs were preferentially expressed in other tissues. Our results establish a clear link between structural genomic variation and cell-type-specific betalain biosynthesis, providing molecular insight into pigment regulation and subgenome specialization in allotetraploid quinoa.

plant biology↗

bioRxiv2025

A cross-species spatial transcriptomic atlas of the human and non-human primate basal ganglia

The basal ganglia are interconnected subcortical nuclei with complex topographical organization that orchestrate goal-directed behaviors and are implicated in neurodegenerative movement disorders. We generated a cellular-resolution, spatial transcriptomic atlas of the basal ganglia in human, rhesus macaque, and common marmoset, sampling over one million cells in each species. By integrating spatial data with a cross-species, consensus snRNA-seq cell type taxonomy, this atlas reveals conserved principles of molecular organization within and across structures. The cellular architecture is complex but highly stereotyped, with gene expression gradients superimposed onto discrete compartments. Extensive spatial sampling illuminates 3D gradients of molecular organization in the striatum and reveals cell type-specific core and shell compartments in the primate internal globus pallidus, which is conserved with mouse. This unified, cross-species spatial transcriptomic atlas will be a foundational resource for characterizing the molecular and functional organization of the basal ganglia and their roles in health and disease.

neuroscience↗

bioRxiv2025

Spatial patterning of transcriptional and regulatory programs in the primate subcortex

Mammalian brain cell identity is shaped by intrinsic factors and external context. We present a spatially resolved transcriptomic and gene regulatory atlas of cell types across all subcortical regions in a primate, the common marmoset. Dense sampling and cross-species integration revealed spatially precise neuronal assemblies, including in complex midbrain and diencephalic structures. Chromatin accessibility and transcriptional identity are spatially tuned within and across subcortical structures; spatial gradients within hippocampal subfields are orchestrated by graded transcription factors acting through graded enhancers. The primate-expanded thalamic GABAergic population shares transcriptional and regulatory syntax with conserved midbrain populations, reflecting an evolutionary adaptation compared with rodents. Similar regional expression across cell types can arise by distinct regulatory architectures, as for telencephalic astrocytes and neurons. Conversely, distant cell types can share regulatory programs despite divergent identities: striatal GABAergic medium spiny neurons and telencephalic glutamatergic neurons share a postsynaptic regulatory program despite divergent lineage, region, and neurotransmitter identity.

neuroscience↗

bioRxiv2025

Next-generation enhancer AAVs for selective interspecies targeting of midbrain dopaminergic neurons

Using single-nucleus multiomic profiling of the marmoset midbrain, we develop and benchmark enhancer-AAVs to selectively access dopamine (DA) neurons in wild-type animals without combinatorial systems. In vivo candidate screenings identified one highly specific DA enhancer, cjDAE8, in both mice and marmosets. To overcome low-level off-target (leaky) expression, a common limitation for enhancer AAVs, we engineered next-generation AAV backbones that strengthen expression while minimizing leakiness. Quantitative histology comparing natural versus antibody-amplified fluorescence defined AAV doses to achieve high labeling efficiency with greater than 90-95% DA-neuron specificity across species and injection routes. We further demonstrate applications of DA-enhancer-AAVs for (i) retrograde targeting of projection-defined DA populations in marmoset, (ii) fiber-photometric recording of divergent DA-axonal dynamics in striatal subregions, and (iii) optogenetic VTA-DA self-stimulation in mice. Our results establish a resource for cross-species DA targeting and two practical guidelines: backbone context critically shapes enhancer performance, and antibody-amplified readouts rigorously assess specificity.

neuroscience↗

bioRxiv2025

Targeted α-Synuclein mRNA Degradation by PMO-Based RNA-Degrading Chimeras

-Synucleinopathies are devastating neurodegenerative diseases characterized by pathological accumulation of a neuronal protein, -synuclein (Syn). Lowering soluble Syn levels is a promising therapeutic strategy to limit aggregation and neurotoxicity, but directly targeting this protein is hindered by its intrinsically disordered structure and other factors, such as its conformational heterogeneity and intracellular drug delivery barriers. Consequently, increasing attention has been directed toward targeting the SNCA transcript, which encodes Syn. Here, we developed phosphorodiamidate morpholino oligonucleotide (PMO)-based RNA-degrading chimeras (RDCs) that selectively bind the 5' untranslated region of SNCA mRNA and recruit RNase L for targeted RNA degradation. Through the systematic evaluation of 10 RDCs, we identified and optimized 4-D1, which effectively reduced SNCA mRNA and Syn protein expression in HEK293T cells in an RNase L-dependent manner. 4-D1 lowered SNCA transcript and Syn protein levels in both primary cortical neurons from humanized SNCA mice and in human induced pluripotent stem cell-derived cortical neurons. This reduction prevented prion-like seeding induced by patient-derived Syn fibrils and protected neurons from fibril-induced cytotoxicity. Finally, in vivo studies confirmed the efficacy of 4-D1 in reducing Syn mRNA expression in humanized SNCA mice. These findings indicate that PMO-based RDCs may represent a promising therapeutic modality for -synucleinopathies. Significance StatementAbnormal aggregation of the neuronal protein -synuclein is central to Parkinsons disease and related disorders, yet therapeutic candidates that directly target this protein have yet to demonstrate efficacy. in clinical trials. We developed a new strategy that lowers -synuclein production at the RNA level using phosphorodiamidate morpholino oligonucleotide (PMO)-based RNA-degrading chimeras (RDCs). These molecules recruit a natural RNA-degrading enzyme to selectively destroy the RNA transcript encoding -synuclein. Our lead RDC reduced -synuclein levels in cultured cells, humanized mouse and human neurons, blocked -synuclein pathological aggregation, and protected neurons from toxicity. This study establishes RDCs as a promising therapeutic platform for Parkinsons disease and other neurodegenerative diseases driven by -synuclein.

biochemistry↗

bioRxiv2025

InsP3R signaling mediates mitochondrial stress-induced longevity through actomyosin-dependent mitochondrial dynamics

Certain forms of mitochondrial impairment confer longevity, while mitochondrial dysfunction arising from aging and disease-associated mutations triggers severe pathogenesis. The adaptive pathways that distinguish benefit from pathology remain unclear. Here we reveal that longevity induced by mitochondrial Complex I/nuo-6 mutation in C. elegans is dependent on the endoplasmic reticulum (ER) Ca2+ channel, InsP3R. We find that the InsP3R promotes mitochondrial respiration, but the mitochondrial calcium uniporter is dispensable for both respiration and lifespan extension in Complex I mutants, suggesting InsP3R action is independent of matrix Ca2+ flux. Transcriptomic profiling and imaging reveal a previously unrecognized role for the InsP3R in regulating mitochondrial scaling, where InsP3R impairment results in maladaptive hyper-expansion of dysfunctional mitochondrial networks. We reveal a conserved InsP3R signaling axis through which calmodulin and actomyosin remodeling machineries, including Arp2/3, formin FHOD-1, and MLCK, constrain mitochondrial expansion and promote longevity. Disruption of actin remodeling or autophagy mimics InsP3R loss. Conversely, driving fragmentation ameliorates mitochondrial expansion and rescues longevity, supporting a model in which InsP3R-dependent actin remodeling sustains mitochondrial turnover. These findings establish an inter-organelle signaling axis by which ER calcium release orchestrates mitochondrial-based longevity through cytoskeletal effectors.

physiology↗

bioRxiv2025

Cellular and molecular underpinnings of functional networks in the human brain

Understanding how cellular and molecular architecture underpins the large-scale organization of human brain function is a central challenge in neuroscience. By integrating transcriptomic (microarray and single-nucleus RNA-sequencing), molecular imaging, and neuroimaging datasets, we observe spatial correspondences indicating that the distributions of diverse cell types, neurotransmitter systems, and mitochondrial phenotypes align with intrinsic connectivity networks (ICNs). These associations extend beyond local correspondence to reflect network-level structure: inter-ICN similarity networks derived from cellular and molecular profiles recapitulate static and dynamic patterns of functional network connectivity (FNC), mirroring canonical functional domains. Mediation analyses reveal that specific ICNs mediate the relationship between microscale cell-type architecture and domain-specific cognitive processes, while FNCs capture mediating pathways linking cell-type and neurotransmitter similarity networks to cognitive organization. Together, our findings show that the brains functional architecture systematically aligns with cellular and molecular organization, which may constrain functional network formation and contribute to the neural basis of cognition.

neuroscience↗

bioRxiv2025

Key genes and pathways in asparagine metabolism in Alzheimers Disease: a bioinformatics approach

BackgroundAsparagine (Asn) metabolism is essential for maintaining cellular homeostasis and supporting neuronal energy demands. Recent studies have suggested its dysregulation may contribute to Alzheimers disease (AD) pathogenesis; however, the specific genes and regulatory mechanisms involved remain incompletely understood. MethodsFour publicly available microarray datasets (GSE5281, GSE29378, GSE36980, and GSE138260) were utilized to investigate genes with differential expression between control and AD samples. Asparagine metabolism-related genes (AMGs) were retrieved from the GeneCards database, and their intersection with DEGs yielded candidate asparagine metabolism-related differentially expressed genes (AMG-DEGs). Functional enrichment analysis (Gene Set Enrichment Analysis, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes), protein-protein interaction (PPI) network analysis, and centrality scoring identified hub genes. Regulatory mechanisms were investigated through construction of competing endogenous RNA and transcription factor networks. Potential therapeutic compounds were predicted via drug-gene enrichment and evaluated using molecular docking simulations. ResultsThirty-nine AMG-DEGs were identified and found to be enriched in neurodevelopmental, synaptic transmission, and inflammatory signaling pathways. PPI analysis and centrality screening revealed seven hub genes (HPRT1, GAD2, TUBB3, GFAP, CD44, CCL2, and NFKBIA). Regulatory network analysis highlighted specific miRNAs, long non-coding RNAs, and transcription factors involved in their modulation. Drug screening and docking identified Bathocuproine disulfonate, DL-Mevalonic acid, and Phenethyl isothiocyanate as promising compounds with strong binding affinities to hub proteins. ConclusionThis study comprehensively maps the dysregulation of asparagine metabolism in Alzheimers disease and reveals a set of hub genes and regulatory elements potentially involved in disease progression. The predicted therapeutic compounds provide a foundation for further experimental validation and may contribute to the development of novel metabolism-targeted strategies for AD treatment.

neuroscience↗

bioRxiv2025

Housekeeping genes are enriched in rheumatoid arthritis-related genes

Housekeeping genes are often considered to be stably expressed in any tissue, cell, or disease state, and the relationship between housekeeping genes and rheumatoid arthritis (RA) has never been systematically analyzed. Therefore we aimed to explore whether housekeeping genes are abnormally expressed in RA by analyzing 15 datasets that were filtered from 140 gene expression profiles. By cumulative hypergeometric test, for 73.3% (11/15) of the datasets, housekeeping genes were significantly (p < 0.05) enriched in differentially expressed genes (DEGs) between RA patients and healthy controls. Using the relative enrichment factor (Re) as an effect size, a Meta-analysis strategy was adopted to integrate the individual results. The logarithmic Re estimation for multiple studies was 0.48 with the 95% confidence interval ranging from 0.17 to 0.80. The combined effect size was significantly higher than that of the randomized case (p = 0.0012) suggesting a consistent result with the hypergeometric test. The robustness of results was verified by sensitivity and subgroup analyses. Furthermore, the expression fluctuation of housekeeping genes was higher in RA patients than healthy controls and the correlation between DNA methylation and gene expression of housekeeping genes was significantly higher than that of non-housekeeping genes, which indicates the potential epigenetic regulation relationship between housekeeping genes and the pathogenesis of RA. This study identified for the first time a significant enrichment of housekeeping genes in DEGs of RA, which might provide new perspectives for understanding the potential role of housekeeping genes in RA.

bioinformatics↗

bioRxiv2024

Biophysical modeling of thalamic reticular nucleus subpopulations and their differential contribution to network dynamics

The burst firing mode of thalamic reticular neurons plays a pivotal role in the generation and maintenance of sleep rhythms and is implicated in sleep-related deficits characteristic of neurodevelopmental disorders. Although several models of reticular neurons have been developed to date, we currently lack a biophysically detailed model able to accurately reproduce the heterogeneity of burst firing observed experimentally. Using electrophysiology recordings of patch-clamped fluorescently tagged Spp1+ and Ecel1+ reticular neurons, we leverage a previously established statistical framework to introduce differentiation of cell types in model thalamic reticular neurons. We developed a population of biophysically detailed models of thalamic reticular neurons that capture the diversity of their firing properties, particularly their ability to generate rebound bursts. These models incorporate key ion channels, such as T-type Ca2+ and small conductance potassium channels (SK), and enable systematic investigations into the impact of these channels on single-cell dynamics. By integrating these models into a thalamic microcircuit, we demonstrate that T-type Ca2+ and SK channel conductances have opposing effects on spindle oscillations. We identify a simple relationship between these conductances and the peak firing frequency of spindles, maintained across circuits with mixed reticular neuron populations, providing a framework for understanding how ion channel expression influences thalamic network dynamics. Collectively, these models establish a foundation for relating intrinsic cellular properties of reticular cell populations to network-level activity in both healthy and pathological conditions.

neuroscience↗