Biology subjects

Zhang, J.

Publications and source records attributed to Zhang, J..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Dual role of the RIG-I 2CARD as a signaling module and a brake on dsRNA translocation

RIG-I is an innate immune receptor for viral double-stranded RNA (dsRNA). Upon binding dsRNA, RIG-I nucleates MAVS filaments through its two caspase activation and recruitment domains (2CARD). However, how the 2CARD behaves during activation has remained unclear. Using high-speed atomic force microscopy, we visualized the 2CARD in full-length RIG-I across its apo, dsRNA-bound, translocating, multimeric, and polyubiquitin-bound states. Protrusions consistent with the 2CARD appeared only transiently in the apo state, whereas a mobile 2CARD emerged upon RNA binding. During ATP-driven translocation, wild-type RIG-I moved approximately twofold slower and showed more frequent pauses and multimers than RIG-I {Delta}2CARD. Within multimers, 2CARDs formed a complex that polyubiquitin stabilized into larger, dsRNA-deforming assemblies. These findings reveal the 2CARD as a brake on the RIG-I motor, beyond signaling.

biophysics↗

bioRxiv2026

Endothelial CD36 links arteriolar remodeling to metabolic and immune alterations in Alzheimer's disease

Alzheimer's disease (AD) is accompanied by profound cerebrovascular dysfunction, yet it remains unclear whether endothelial abnormalities reflect only vascular injury or altered regulatory states connecting vascular remodeling with metabolic and immune function. We integrated human brain transcriptomic and histopathological data with complementary mouse genetic and human iPSC-derived endothelial models to examine a CD36-centered endothelial-state framework in AD. Analysis of the Seattle Alzheimer's Disease Brain Cell Atlas identified three CD36-expressing endothelial populations; intermediate-CD36 Endo 2 predominated in both reference and AD samples, although the relative subset distributions differed. In hippocampal and cortical tissue from six AD patients, endothelial CD36 expression was observed in structurally abnormal arterioles with disrupted mural organization. In complementary mouse studies, endothelial PKD1 deficiency was accompanied by increased vascular CD36 and cerebrovascular abnormalities, whereas endothelial CD36 deletion altered lipid-metabolic and innate-immune-associated transcriptional programs, including AD-relevant genes and pathways, under metabolic-inflammatory stress. To assess whether distinct human endothelial backgrounds remained pharmacologically responsive, we treated control and CRISPR-engineered PSEN1 E276A iPSC-derived ECs with GS4898, a small molecule previously linked to arterial specification. Both maintained endothelial identity but displayed different baseline transcriptional profiles and shared as well as cell-line-dependent responses to GS4898. Together, our study identifies a CD36-associated vascular phenotype in human AD, demonstrates CD36-dependent regulation of brain endothelial metabolic-immune transcriptional programs in vivo, and reveals endothelial transcriptional responsiveness to pharmacologic perturbation. The observed endothelial transcriptional plasticity may provide a basis for developing state-selective therapeutic strategies targeting cerebrovascular dysfunction in AD.

neuroscience↗

bioRxiv2026

FLASH X-rays preserve neutrophil chromatin to boost antitumor immunity

Ultrahigh dose-rate FLASH radiotherapy spares normal tissue while preserving antitumor activity, positioning it as a promising technology in radiation oncology, but its immunomodulatory mechanisms remain elusive. Here, using a bilateral subcutaneous tumor model in mice, we show that 8-Gy FLASH X-rays, versus an equal dose of conventional dose-rate (CONV) X-rays, elicit a robust abscopal antitumor effect with anti-PD-1 therapy. Single-cell transcriptome and T cell receptor (TCR) profiling reveal that FLASH X-rays plus anti-PD-1 enhance antitumor immune infiltration and TCR clonal expansion in both irradiated and abscopal tumor lesions. Mechanistically, the ultrashort temporal continuity of FLASH dose delivery conserves chromatin compaction in neutrophils during exposure and inhibits neutrophil extracellular trap (NET) formation, thereby dismantling NET-mediated CD8+ T-cell exclusion within primary tumors. Conversely, CONV or split-dose FLASH X-rays induce marked chromatin modifications prior to dose completion, leading to chromatin hyper-relaxation which promotes NETosis and consequently abrogates systemic antitumor immunity. Notably, this detrimental effect can be reversed by pharmacologically suppressing PARylation-mediated chromatin modification and decondensation in neutrophils. These findings identify radiation-induced aberrant chromatin relaxation in neutrophils as a critical determinant of radioimmunotherapy outcomes, providing a rationale for redefining the FLASH effect and advancing its clinical translation.

cancer biology↗

bioRxiv2026

Cross-species analysis identifies APOBEC3-associated spliceosomal snRNA hypermutability

Spliceosomal small nuclear RNA (snRNA) genes show unusually high germline mutation rates, with R-loop formation previously implicated in this mutability. Our cross-species rare-variant and de novo mutation analyses show that hypermutability is concentrated in RNA polymerase II-transcribed spliceosomal snRNA genes, with strong enrichment in primates but a much weaker excess in rodents and chicken, consistent with lineage differences in APOBEC3 repertoires. Human Pol II-transcribed spliceosomal snRNA genes show mutational strand asymmetry, APOBEC3-associated mutational signatures and strong APOBEC3B binding signals. R-loops are also frequent at these loci, including in mouse genes with much weaker hypermutability, indicating that R-loop formation alone is insufficient to explain the phenotype. Together, cross-species comparisons support lineage-specific APOBEC3 activity, rather than R-loop formation alone, as a major contributor to spliceosomal snRNA gene hypermutability.

genomics↗

bioRxiv2026

A 21-Color Spectral Flow Cytometry Panel for Comprehensive Immunophenotyping of Rat Tissues and a Companion 9-Color T-Cell Functional Assay

Although rats are crucial translational research models due to their immunological homology and surgical feasibility, the scarcity of conjugated antibodies has hampered high-dimensional immune profiling. To bridge this gap, we created a synergistic two-panel method that uses full-spectral flow cytometry: a 21-color comprehensive immunophenotyping panel and a 9-color intracellular cytokine staining (ICS) panel. The 21-color panel navigates the limited fluorophore pool and maps innate and adaptive lineages at high resolution. While it can be used to profile neutrophils and monocytes in peripheral blood it reaches its full potential in lymphoid organs, allowing for the simultaneous evaluation of tissue-resident macrophages, dendritic cells, T cell differentiation (including Tregs), and APC function. Based on this phenotypic paradigm, the 9-color ICS panel dissects effector T cell activation and Th1/Th2/Th17 cytokine production. Furthermore, we reserved the PE color during panel creation, allowing for the use of antibodies and probes with PE or comparable fluorophores in conjunction with this panel, hence increasing overall flexibility. This combination technique, designed for rat peripheral blood, spleen, and lymph nodes, combines panoramic phenotyping with functional analysis, offering an adaptable foundation for complicated tissue microenvironments in tumor immunology, rheumatology, and autoimmunity research.

immunology↗

bioRxiv2026

Neprilysin 1 in the Mushroom Body controls Feeding behavior by regulating SIFamide levels in Drosophila melanogaster

Feeding-related behavior in Drosophila melanogaster encompasses olfactory and gustatory detection of odors, foraging, and food intake. In Drosophila melanogaster, the neuropeptide SIFamide (SIFa), has been shown to integrate hunger signals to promote feeding in Drosophila and is considered a central regulator of mutually exclusive behavioral states. Here, we identify the mushroom bodies as a key downstream circuit of SIFamidergic neurons for regulation of food-seeking and feeding. Furthermore, we show that mushroom bodies are not merely downstream effectors but actively shape SIFamidergic signaling through the peptidase Neprilysin 1 for which SIFamide is a substrate. Thus, SIFa signaling is embedded within a feedforward-feedback circuit that couples internal state to the selection and execution of feeding behavior. We propose that the distinct neuronal subtypes postsynaptic to the elaborately arborized SIFamidergic neurons define discrete neuronal subroutines that differentially control the mutually exclusive behaviors related to sexual reproduction, sleep and feeding. Our findings reveal an evolutionary ancient peptidergic system that is modified by recruitment of novel genes for the flexible control of distinct behavioral programs and feeding strategies.

animal behavior and cognition↗

bioRxiv2026

UniMedSeg: Unified Multi-Modal Medical Image Segmentation via Uncertainty Guided Encoding and Frequency-Spatial Dual-Prompt Decoding

Text-driven medical image segmentation demands unified models based on multi-modal learning, capable of processing diverse imaging modalities while providing spatially reliable prediction estimates for clinical practice. Nevertheless, existing vision-language model solutions suffer from poor domain generalization and exhibit limited capability for uncertainty estimation to model the cumulative unreliability of cross-modal alignment across network layers. In this paper, we propose UniMedSeg, a unified vision-language framework for multi-modal medical image segmentation built upon frozen pre-trained vision-language backbones. Our framework incorporates modality-aware adaptation, cross-layer uncertainty-guided encoding, and a frequency-spatial dual-prompt decoder, wherein the progressive uncertainty propagation mechanism of the encoder suppresses misleading cross-modal features, whereas the decoder disentangles anatomical structure and boundary details in the frequency domain under dual textual prompts. Auxiliary losses further sharpen boundary representations and calibrate pixel-wise uncertainty maps. Extensive experiments demonstrate that UniMedSeg preserves competitive in-domain segmentation performance, improves domain generalization, and yields clinically useful spatial risk estimation.

pathology↗

bioRxiv2026

Ligand-specific endothelial Notch signaling coordinates brain pericyte specification and expansion

Pericyte specification and expansion must be coordinated with vascular growth to establish a functional cerebrovascular network, yet how endothelial signals control these distinct developmental transitions remains incompletely understood. Here, using genetic manipulation, single-cell transcriptomic analysis, and longitudinal in vivo imaging in zebrafish, we identify ligand-specific endothelial Notch signaling as a mechanism coordinating brain pericyte development. Endothelial Jag2b is required for efficient pericyte specification from pericerebral progenitor pools and subsequently promotes Notch-dependent pericyte proliferation and population expansion. By contrast, endothelial Dll4 restrains pericyte proliferation and functionally opposes Jag2b-dependent expansion, demonstrating that distinct endothelial Notch ligands generate different developmental outputs. Endothelial Notch activation increases jag2b expression, and genetic interaction analyses establish Jag2b as an important mediator of Notch-dependent pericyte expansion. Moreover, genetic disruption of piezo1 reduces brain pericyte abundance, whereas endothelial jag2b expression rescues this phenotype, placing Jag2b downstream of Piezo1-dependent hemodynamic signaling. Together, these findings reveal a ligand-specific endothelial Notch program that integrates hemodynamic cues with endothelial-pericyte communication to coordinate the specification and expansion of brain pericytes during cerebrovascular development.

developmental biology↗

bioRxiv2026

Interspecific differences in second-site modifiers reshape dominance in a Mendelian trait by altering environmental plasticity

Dominance is an important and evolvable property of the genotype-phenotype map. A longstanding debate in evolutionary genetics concerns whether dominance is determined primarily by intrinsic properties of alleles at the focal locus or by modifiers elsewhere in the genome. Theoretical models show that second-site modifiers of dominance can evolve under some conditions. However, direct empirical tests of these models are rare because they require holding the focal heterozygous genotype constant while changing the rest of the genome. In the Drosophila montium species subgroup, female pigmentation is a Mendelian trait controlled by a single gene, POU domain motif 3 (pdm3), but the dominance relationships between pdm3 alleles differ among species. Using reciprocal introgressions among three closely related species, we compared females carrying the same Light/Dark pdm3 allele combinations in different homozygous or heterozygous genomic backgrounds and across different temperatures. In both species-pair comparisons, changing genomic background significantly altered the phenotype of identical pdm3 heterozygotes, demonstrating the existence of second-site modifiers of dominance. The effects of dominance modifiers depend on the particular pair of pdm3 alleles and on rearing temperature. These results show that dominance in this system is a genotype-by-genotype-by-environment trait, rather than a fixed attribute of individual alleles. The finding that second-site modifiers can alter dominance by reshaping reaction norms provides a developmental mechanism that links the evolution of dominance to phenotypic plasticity.

evolutionary biology↗

bioRxiv2026

An ancestral tRNA maturation enzyme repurposed for cytoplasmic non-coding RNA processing

Ribonuclease Z enzymes remove 3' trailers from precursor tRNAs. In human cells, ELAC2/RNase ZL matures nuclear and mitochondrial pre-tRNAs, whereas the cytosolic short paralog ELAC1/RNase ZS repairs ANKZF1-cleaved tRNAs, but its broader substrate repertoire remains unclear. We investigated ELAC1 function using transcriptome profiling, small RNA sequencing, CLIP-seq, and biochemical reconstitution. ELAC1 was dispensable for canonical tRNA processing but associated with structured RNA polymerase III transcripts, prominently Y RNAs and vault RNAs (vtRNAs). Purified ELAC1 cleaved all four human vtRNAs near their 3' ends, with high-resolution mapping identifying a conserved cleavage position within the 3' extension. Efficient cleavage required structural features of the vtRNA terminal region. In contrast, ELAC2 showed little or no vtRNA cleavage under the conditions tested and displayed stricter substrate and cleavage-site selection on pre-tRNA. Loss and re-expression of ELAC1 altered structured ncRNA abundance and small-RNA end profiles. These findings identify vtRNAs as direct ELAC1 substrates and support functional specialization of human ELAC paralogs, with ELAC2 favoring precise pre-tRNA maturation and ELAC1 exhibiting broader RNA substrate specificity.

molecular biology↗

bioRxiv2026

TorPause: Efficient Static Organ Preservation for Transplants

Transplantation is limited by how long organs survive outside the body. Existing preservation methods slow metabolism or sustain physiological support, but neither eliminates ischemia-reperfusion injury (IRI), which shortens storage and drives organ discard. Embryonic diapause and hibernation show that mammalian cells retain a latent capacity for reversible metabolic arrest. Screening the PI3K-mTOR axis, we identified a dual inhibitor that pauses embryonic stem cells reversibly at ambient oxygen and holds intact mouse embryos in arrest for 11 days. Combined with a mitochondria-targeted hydrogen sulfide donor, this yields TorPause: a two-component flush pairing metabolic pausing with mitochondrial protection, compatible with existing preservation protocols. In a rat liver transplantation model, TorPause reduced structural injury and improved recipient survival after severe warm ischemic storage, potentially expanding the usable donor pool.

developmental biology↗

bioRxiv2026

De novo protein design in an expanded chemical space

Generative protein design has made sequence and structure programmable, yet its chemical alphabet remains largely confined to the canonical twenty. Here, we establish CheMoDesign, an experimentally validated generative framework for designing proteins de novo around user-specified chemistry. CheMoDesign weakens pair-representation conditioning in a pretrained all-atom structure-prediction model while preserving chemical anchors, then refines generated backbones through sequence-conditioned denoising. By treating post-translational modifications, synthetic residues, and chemical modifications as user-defined building blocks, the framework generated proteins with chemistry-dependent recognition and reactivity in single-round experimental campaigns. Sulfotyrosine and nitrotyrosine enabled modification-dependent recognition of thrombin and HER2, respectively. Genetically encoded noncanonical residues enabled bioorthogonal affinity switching and light- or proximity-triggered covalent target capture. Post-expression chemical modifications yielded a light-activated covalent PD-L1 binder and an isoform-selective CA IX inhibitor (KD = 45 nM) designed to engage catalytic Zn2+;. CheMoDesign makes chemical mechanism a programmable dimension of de novo protein design.

biochemistry↗

bioRxiv2026

Cross-Tissue Inflammatory Convergence Supports a Putative Muscle-Brain Axis in Alzheimer's Disease

Background Reduced muscle strength is associated with cognitive decline and Alzheimer's disease (AD), suggesting that skeletal-muscle aging and AD-related neurodegeneration may share biological mechanisms. Vascular dysfunction, immune activation, and extracellular-matrix remodeling have been implicated in both tissues, but the extent of shared cellular and molecular programs remains unclear. We investigated cross-tissue transcriptional programs in aging skeletal muscle and AD-related brain tissue and evaluated whether related signals are detectable in peripheral blood. Methods We analyzed independent, unpaired human transcriptomic datasets from skeletal muscle (23 donors), the SEA-AD middle temporal gyrus atlas (84 donors), and peripheral blood. Donor-aware models identified age-associated changes in muscle and transcriptomic changes across continuous pseudoprogression score (CPS) in brain. Cross-tissue comparisons focused on 30 brain donors within an early CPS window. Shared tissue-derived programs were assessed in peripheral blood mononuclear cells and independently tested in frailty bulk-blood and Alzheimer's Disease Neuroimaging Initiative (ADNI) whole-blood datasets. CellOracle simulations were used to prioritize candidate transcriptional regulators. Results Aging muscle showed increased inflammatory, extracellular-matrix, and stromal communication programs. During early AD-related brain progression, vascular and immune populations showed increasing inflammatory and matrix-associated activity together with shifts in intercellular communication. Cross-tissue analysis identified six concordantly enriched pathways comprising 109 leading-edge genes in endothelial populations and four pathways comprising 51 genes in myeloid populations. Related peripheral-blood signatures varied across cohorts and cell types. However, in independent frailty and ADNI mild cognitive impairment and AD datasets, 23 of 30 predefined tissue-derived pathway-subset tests showed significant positive enrichment after false-discovery-rate correction, whereas individual gene-level bulk-blood associations did not survive correction. CellOracle analyses prioritized ETS2 and BHLHE40 as exploratory endothelial regulators whose simulated perturbation consistently reduced selected shared program scores across tissues. Conclusions Aging skeletal muscle and AD-related brain tissue exhibit convergent endothelial and myeloid inflammatory programs, with related pathway-level signals detectable in peripheral blood. These cross-tissue programs and candidate endothelial regulators provide testable hypotheses for mechanisms linking systemic aging, muscle dysfunction, and AD-related neurodegeneration.

neuroscience↗

bioRxiv2026

Adenosylhomocysteinase drives epigenetic and metabolic reprogramming in ZFTA-RELA ependymoma

Supratentorial ependymomas (ST-EPNs) are aggressive pediatric brain tumors predominantly driven by the recurrent ZFTA-RELA fusion, an oncogenic chromatin regulator that establishes an aberrant transcriptional program. Although metabolic pathways modulate epigenetic regulation by controlling the availability of metabolic cofactors, how ZFTA-RELA coordinates metabolic reprogramming with epigenetic regulation is not well understood. Here, we show that ZFTA-RELA-positive ependymomas exhibit enhanced methionine dependency, elevated adenosyl homocysteinase (AHCY) expression, and epigenetically control aspartate metabolism for tumor growth. Mechanistically, ZFTA-RELA upregulates AHCY, increasing cellular methylation potential which promotes H3K4me3-dependent expression of CAD, the first enzyme complex of de novo pyrimidine biosynthesis, while simultaneously enforcing H3K27me3 mediated repression of ASNS, which encodes asparagine synthetase. Through this coordinated epigenetic program, aspartate utilization is directed toward pyrimidine biosynthesis while endogenous asparagine production is limited. Restricting S-adenosylmethionine availability or genetically or pharmacologically inhibiting AHCY reverses these epigenetic states, leading to CAD downregulation, ASNS upregulation, impaired nucleotide synthesis, and suppression of tumor growth in vitro and in vivo. Similarly, EZH2 inhibition also restores ASNS expression and suppresses tumor proliferation. These findings suggest that ZFTA-RELA EPN maintain ASNS-low phenotype which conditionally make them dependent on extracellular asparagine. We further show that enhanced de novo pyrimidine synthesis not only supports nucleotide production but also provides UDP-sugars required for N-glycosylation and stabilization of the asparagine transporter SLC1A5, thereby promoting extracellular asparagine uptake and tumor proliferation. Collectively, our findings identify AHCY as a critical metabolic regulator of epigenetic and metabolic reprogramming that drives pyrimidine synthesis and establishes extracellular asparagine dependency, revealing actionable metabolic vulnerabilities in ZFTA-RELA-positive ST-EPNs.

cancer biology↗

bioRxiv2026

MERFISH-based pooled genetic screening reveals cell non-autonomous phenotypes in intact tissue

Genetic perturbations can reshape both the state of a targeted cell and the behavior of neighboring cells. Measuring these effects systematically in intact tissues requires pooled screening methods that jointly identify perturbations, molecular phenotypes, and spatial context of individual cells. Here, we report an imaging-based pooled screening method that detects perturbation identities and endogenous RNAs without enzymatic amplification. Relative to our previous enzymatic-amplification-based workflow, amplification-free MERFISH detection with direct hybridization increased recovery of perturbation barcodes by ~10-fold and endogenous transcripts by 2.5-fold, improving perturbation assignment as well as molecular profiling of both perturbed and neighboring cells. Applying this method to a genetic mosaic mouse liver screen targeting ~200 genes in hepatocytes, we profiled 1.5 million cells in intact tissues and mapped both cell-autonomous responses of perturbed hepatocytes and cell non-autonomous changes in neighboring immune and vascular populations. These included localized accumulation of pDC-like cells near hepatocytes with impaired V-ATPase function and angiogenic responses in vascular cells near Vhl-perturbed hepatocytes with hypoxia activation. Our method provides a simplified, scalable approach to linking genetic perturbations with cell state, multicellular response, and tissue organization.

genomics↗

bioRxiv2026

Lifespan Trajectories of Resting State Bipolar EEG Power

Normative trajectories of resting state bipolar EEG power over the lifespan were derived from a sample of 5781 participants from the Collaborative Study on the Genetics of Alcoholism (COGA), a large multi site study, using 12,906 observations from ages 12 through 70. Trajectories were analyzed using the means, variances, and correlations of data in seven frequency bands (from low theta to high beta) and 24 bipolar channels obtained from 17 electrodes of the 10-20 system. In order to make the study more useful for understanding EEG in the general population, only subjects never having an alcohol use disorder (AUD) diagnosis were included in the study. Bipolar EEG data is derived from the differencing of the signals in adjacent electrodes, either in a lateral (left-right) or sagittal (anterior-posterior) orientation; each difference is called a channel. The power values for the individual observations were calculated by standard Fourier transform based methods. In all cases there are sharp decreases in EEG power from ages 12 to the early 20s after which there are number of divergent patterns: general increases in the beta frequencies, and mixed patterns of increase and subsequent decrease in the theta and alpha frequencies. In these characteristics the lifespan trajectories presented here are similar to the monopolar trajectories described in our previous study \citet{Cho2026}. Sagittal and lateral bipolar trajectories are similar within each sex and between sexes; the primary difference is the much lower degree of regional difference in the sagittal trajectories as compared to the lateral trajectories. The pairwise inter-frequency (within channel) correlation trajectories between the four theta and alpha frequency bands and the four high alpha and beta frequency bands at each channel show striking sex differences unlike the corresponding monopolar correlations. There are a number of features in the bipolar power trajectories that suggest that the differencing procedure reduces not only local phase synchrony, but also effects of global and regional phase synchrony present in the monopolar data from which the bipolar signals are derived. The inter-frequency correlations at the individual channels are much higher in the bipolar data than the monopolar data, suggesting that global and regional phase synchrony components retained in the monopolar data have greater frequency specificity than the more purely local components in the bipolar data. Further analyses to examine many other features of the data will be undertaken in our subsequent work.

neuroscience↗

bioRxiv2026

Breedbase 2.0 - expanding the functionality for traditional breeding and transgenics

Breedbase ( is a comprehensive, web-based, open-source breeding management and analysis software for plant breeding that was introduced to address gaps with existing software for plant breeding data. Breedbase is continually improved and developed, with new features being added as required by the breeding community. Since its inception, the capabilities of Breedbase were improved to better serve the diverse data modeling needs of additional crops beyond our original ensemble of cassava, banana, yam, sweet potato, tomato, rice, and wheat. We describe here major updates that have been made in the past 4 years, including (1) improved handling of repetitive measurements; (2) a redesigned experimental treatments interface; (3) a more fine-grained user permission system; (4) improved trial quality control workflows; (5) intercropping support; (6) the addition of a decision meeting feature that helps decision makers make the best selection with the available data; (7) transgenics and tracking tools and finally, (8) an improved field layout tool which consolidates several trials in one field. These new features integrate seamlessly with the previous feature set of Breedbase - making it one of the most feature rich breeding management softwares available.

bioinformatics↗

bioRxiv2026

A learned oral signal drives long-lasting thirst satiation

Drinking quenches thirst long before the ingested water has been absorbed. Here we investigate the mechanism by combining sham drinking, which uncouples water ingestion from rehydration, with recordings of thirst-promoting neurons in the brain. We show that sham drinking suppresses thirst and rapidly inhibits thirst-promoting neurons despite no water absorption. Remarkably, this suppression of thirst neurons in the absence of rehydration is proportional to the amount of water consumed and persists for tens of minutes after drinking has stopped. This sustained inhibition is triggered by passage of water through the oral cavity, but not licking or swallowing alone, and undergoes extinction with repeated sham drinking, indicating it is learned. Complementary experiments using hypertonic saline demonstrate this learning is bidirectional. These findings reveal that the experience of rapid thirst quenching is not a hard-wired response to the consumption of water, but rather a learned prediction of future bodily state.

neuroscience↗