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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2025

Assisted gene flow yields Acropora palmata corals with robust physiological performance under warmer water temperatures in a land-based nursery

Assisted gene flow (AGF) is a conservation approach that facilitates the spread of alleles and may accelerate the recovery of genetically depauperate cohorts. The threatened Caribbean coral Acropora palmata is approaching regional extinction within the western Atlantic partly due to increasing water temperatures associated with global climate change. Previously, AGF was conducted by crossing gametes collected from three regions (Curacao - CU, Florida - FL, and Puerto Rico - PR) characterized by contrasting temperature regimes and low gene flow between them. Here, we tested the thermal tolerance of these AGF cohorts in comparison to purebred Florida and Curacao cohorts. Exposure to high temperatures resulted in few physiological changes, likely because the corals hosted the thermally tolerant algal symbiont, Durusdinium trenchii. However, the FL x FL cohort was the most sensitive to the high temperatures with a significant reduction in net photosynthesis and maximum electron transport rate under this treatment. Like the phenotypic responses, gene expression changes in response to heat stress were muted overall. Consequently, there was little power to detect correlations between genotype and phenotype. Relative to mid-parent values, CUxFL AGF cohorts showed 26 overexpressed and 48 underexpressed genes. Differentially expressed genes included known stress responders. Importantly, hybrid crosses harbored 879 private alleles that were previously not recovered in representative genets from Florida and thus carry important conservation value. These findings suggest that AGF corals not only carry novel alleles but also represent novel gene expression patterns.

ecology↗

bioRxiv2025

A small periplasmic protein governs broad physiological adaptations in Vibrio cholerae via regulation of the DbfRS two-component system

Two-component signaling pathways allow bacteria to sense and respond to environmental changes, yet the sensory mechanisms of many remain poorly understood. In the pathogen Vibrio cholerae, the DbfRS two-component system controls the biofilm lifecycle, a critical process for environmental persistence and host colonization. Here, we identified DbfQ, a small periplasmic protein encoded adjacent to dbfRS, as a direct modulator of pathway activity. DbfQ directly binds the sensory domain of the histidine kinase DbfS, shifting it toward phosphatase activity and promoting biofilm dispersal. In contrast, outer membrane perturbations, caused by mutations in lipopolysaccharide biosynthesis genes or membrane-damaging antimicrobials, activate phosphorylation of the response regulator DbfR. Transcriptomic analyses reveal that DbfR phosphorylation leads to broad transcriptional changes spanning genes involved in biofilm formation, central metabolism, peptidoglycan synthesis, and cellular stress responses. Constitutive DbfR phosphorylation imposes severe fitness costs in an infection model, highlighting this pathway as a potential target for anti-infective therapeutics. We find that dbfQRS-like genetic modules are widely present across bacterial phyla, underscoring their broad relevance in bacterial physiology. Collectively, these findings establish DbfQ as a new class of periplasmic regulator that influences two-component signaling and bacterial adaptation.

microbiology↗

bioRxiv2025

Unreal? A Behavioral, Physiological, and Computational Model of the Sense of Reality

Our awareness of dreams, hallucinations, and illusions reflects an intriguing human capacity to recognize potentially false perceptions, known as the Sense of Reality (SoR). Though central to mental health, the study of SoR has been hindered by the subjective nature of hallucinatory experiences. Here we employed a novel virtual reality paradigm simulating virtual hallucinations, mirroring the phenomenology of clinical hallucinations. Combining psychophysics, physiological recordings, and computational modeling in one exploratory (n = 31) and one preregistered experiment (n = 32), we found that SoR varied with virtual hallucination magnitude and domain. SoR judgments were associated with distinct motor, pupillary, and cardiac responses, allowing classification of virtual hallucination exposure. We present a computational model in which SoR judgments arise from comparing current sensory input to an internal model of the world. Our results shed light on the age-old question how do we know what is real?

neuroscience↗

bioRxiv2025

AMPK is dispensable for physiological podocyte and glomerular functions but prevents glomerular fibrosis in experimental diabetes

AMP-activated protein kinase (AMPK) has been postulated to be crucial in regulating various renal physiology and pathophysiology processes, including energy metabolism, ion and water transport, inflammation, and hypertrophy. However, the specific roles of AMPK in the podocyte, a cell critical for maintaining glomerular filtration, have not been fully explored using genetic model animals. In this study, we generated mice lacking both AMPK 1 and 2 catalytic subunits in glomerular podocytes (pmut). Our findings revealed that, surprisingly, AMPK is dispensable for normal podocyte function. These knockout mice could live as long as their wild-type littermates without showing any pathological alterations in their glomeruli or glomerular function at two years of age. However, under type 1 diabetic conditions, the diabetic pmut mice exhibited increased lipid and collagen accumulation and an elevated expression of mesenchymal proteins in their glomeruli. They also showed more significant albuminuria compared to control diabetic mice. Under high glucose culture conditions, glomeruli isolated from pmut mice demonstrated a reduced expression of mitochondrial genes (e.g., Ndufv2) and increased leakage of mitochondrial components. Additionally, there was heightened expression of genes associated with nucleotide sensing and pro-inflammatory pathways (including mb21d2, IL-1 beta, and NF-kB). These observations suggest that while AMPK is not necessary for podocyte function in healthy kidneys, it is crucial for preventing glomerular fibrosis resulting from lipotoxicity and inflammation under diabetic conditions.

cell biology↗

bioRxiv2025

Quantification of Wnt3a, Wnt5a and Wnt16 Binding to Multiple Frizzleds Under Physiological Conditions using NanoBit/BRET

Upon engagement of one of the 19 secreted Wnt signalling proteins with one of the 10 Frizzled transmembrane Wnt receptors (FZD1-10), a wide variety of cellular Wnt signalling responses can be elicited, the selectivity of which depends on: 1) the specific Wnt-FZD pairing, 2) the participation of Wnt co-receptors, and 3) the cellular context. Co-receptors play a pivotal role in guiding the specificity of Wnt signaling, most notably between {beta}-catenin dependent and independent pathways, where co-receptors such as LRP5/6 and ROR1/2 / PTK7 play major roles, respectively. It remains less understood how specific Wnt/FZD combinations contribute to the selectivity of downstream Wnt signaling and we lack accurate comparative data on their binding properties under physiological conditions. Here, using fluorescently-tagged Wnt3a, Wnt5a and Wnt16 proteins and cell lines expressing HiBiT-tagged Frizzled, we build on our ongoing efforts to provide a complete overview of the biophysical properties of all Wnt/FZD interactions using full-length proteins. Our real-time NanoBRET analysis using living cells expressing low receptor levels provides more accurate quantification of binding and will help us understand how these binary engagements control Wnt signaling outputs. We also provide evidence that LRP6 regulates the binding affinity of Wnt/FZD interactions in the trimeric Wnt-FZD-LRP6 complex.

biochemistry↗

bioRxiv2025

Genome sequencing and physiological characterization of three Neoarthrinium moseri strains

Fungi play essential ecological roles and have been utilized by humans for diverse applications such as industrial enzyme production or as sources of bioactive compounds. Recent research has highlighted the Amphisphaeriales order (Ascomycota) as promising producers of secondary metabolites of pharmaceutical importance. Within this family, the recently established genus Neoarthrinium includes species such as N. brasiliensis, N. lithocarpicola, N. moseri, N. trachycarpi, and N. urticae. Existing literature has primarily focused on the taxonomy and phylogeny of Neoarthrinium, leaving its physiology, ecology, and metabolic potential unexplored. This study presents the first investigation of the metabolic and genomic potential of N. moseri. We describe the isolation of two South-Asian N. moseri strains and the genome sequencing of these strains alongside the Colombian ex-type strain for the species. Comparative genome analysis reveals an exceptionally high number of biosynthetic gene clusters (BGCs), surpassing those of many other fungi in the Amphisphaeriales order. Additionally, the genome of N. moseri contains a diverse repertoire of carbohydrate-active enzymes (CAZymes), supporting its hypothesized ecological role as a phyllosphere fungus (putatively an endophyte and/or saprotroph). Ecophysiological assays, including BIOLOG phenotyping, demonstrate its ability to utilize a broad range of carbon sources, emphasizing ecological versatility. This study highlights N. moseri as a promising candidate for secondary metabolite discovery, providing foundational insights into the metabolic and genomic potential of the Neoarthrinium genus and related fungi.

microbiology↗

bioRxiv2025

Liposome Encapsulation Enables Near-Native Cryo-EM Structural Determination by Shielding Macromolecules from Non-Physiological Interfaces

Cryo-electron microscopy (cryo-EM) has emerged as a very powerful tool for high-resolution structure determination of macromolecule complexes. However, sample preparation remains a major bottleneck in cryo-EM workflows. Most structures were resolved not in a native solution environment, but rather in the non-physiological interfaces such as the air-water interface (AWI), where the folding/unfolding energy landscape of macromolecules may be significantly altered, leading to artifact, preferential orientation, particle disassembly or even denaturation. To address this challenge, we developed a robust, sample-independent method utilizing liposome encapsulation that preserve macromolecules in a solution-like and near native environment throughout sample preparation. Using equine spleen apoferritin and the Escherichia coli (E. coli) ribosome as model systems, we demonstrate efficient particle incorporation into liposomes and successful high-resolution structure determination. Notably, our method yields significantly reduced particle disassembly, denaturation, and preferential orientation compared to samples on holey carbon and graphene grids. We anticipate that this approach will facilitate structural studies of other challenging macromolecular complexes that are sensitive to interfacial effects.

biophysics↗

bioRxiv2025

Transcriptomic and physiological responses of soybean plants subjected to a combination of water deficit and heat stress under field conditions

Water deficit, heat stress, and a combination of water deficit and heat stress are highly disruptive to crop yield worldwide. Unfortunately, the frequency and intensity of these conditions is gradually increasing due to climate change. Previous studies of water deficit and heat stress combination were primarily conducted under controlled growth conditions, revealing that the combination of water deficit and heat stress resulted in the activation of unique stress responses and acclimation pathways. However, whether similar responses to stress combination occur in the field remained largely unknown. Here we report on a two-year field study in which the transcriptomic and physiological responses of vegetative and reproductive tissues of soybean (Glycine max) to water deficit, heat treatment and their combination were studied. Our findings reveal that the transcriptomic responses of soybeans grown in the field are different from those grown under controlled growth chamber conditions. These differences were especially noticeable in plants subjected to the heat or water deficit treatments, and less in plants subjected to the stress combination. In addition, we report that differential transpiration between leaves and pods, that was originally discovered in plants grown under controlled growth conditions, occurs in field grown soybeans in response to heat stress, as well as heat stress combined with water deficit. We hope that the transcriptomic datasets generated by our study will contribute to future studies of crop responses to different stresses in the field, as well as highlight the need for more omics studies of plants grown under field conditions.

plant biology↗

bioRxiv2025

Physiological febrile heat stress increases cytoadhesion through increased protein trafficking of Plasmodium falciparum surface proteins into the red blood cell

Fever is a hallmark of malaria. Several studies have linked febrile temperatures to reduced parasite viability, but also to increased cytoadhesion, a key driver of pathology. However, different mechanisms have been proposed to cause changes in cytoadhesion and parasite sensitivity to heat. Here, we demonstrate that exposure of Plasmodium falciparum-infected red blood cells (iRBCs) to physiologically relevant febrile heat stress (39 {degrees}C), derived from patient data, enhances cytoadhesion through increased trafficking of the major virulence factor PfEMP1 to the iRBC surface. This phenomenon is not limited to PfEMP1 and common laboratory strains, as it extends to the surface nutrient channel PSAC in four clinical isolates of diverse geographic origin. The increased surface protein display occurs without changes in overall protein expression or parasite developmental progression. Using phosphoproteomics and proximity labelling, we find that elevated temperature also increases trafficking and phosphorylation of exported proteins into the RBC. Enhanced export is likely reliant on the presence of a transmembrane domain as shown by NanoLuc reporter assays. Collectively, our results indicate that febrile temperatures commonly experienced during infection can accelerate protein export, likely at the parasitophorous vacuole. This enhanced export following heat stress is relevant because increased cytoadhesion could influence disease severity through earlier iRBC sequestration and elevated bound parasite mass.

cell biology↗

bioRxiv2025

Spatiotemporal dynamics of CD73 in mouse retina under physiological conditions

Adenosine is essential to energy metabolism and neuromodulation in the central nervous system. The retina is a highly energy-demanding neural tissue, and dysregulation of adenosine signaling causes retinal diseases. However, the dynamics of ecto-5-nucleotidase (CD73), a key enzyme for extracellular adenosine generation, remain elusive. Here, we investigate its spatiotemporal profile from development to adulthood using two transgenic mouse lines. We found that CD73 is transiently expressed in the early astrocyte lineage (Embryonic day 16.5 to Postnatal day [P] 3), becomes prominent in the rod-photoreceptor lineage by P3, and appears in the inner nuclear layer from P7 onward. CD73 deletion delays rod-response recovery and shortens the implicit time in scotopic ERG under dim light. These findings indicate that light and other physiological cues influence CD73 expression, which has significant consequences for retinal function, thereby providing a foundation for exploring disease-related alterations in CD73 and designing therapies that restore adenosine homeostasis.

developmental biology↗

bioRxiv2025

Differential Expression and Microsystem Physiology Reveal Predominant and Drug Reversible CFTR-Related Defects in Idiopathic Pancreatitis

Pancreatitis is a potentially fatal and difficult to control exocrine-tissue defect with no FDA approved therapies. Variants of a chloride/bicarbonate transporter cystic fibrosis transmembrane conductance regulator (CFTR) pose multi-fold increased risk of pancreatitis accounting for up to 40% of the patients with idiopathic pancreatitis. However, the relationship between the duct-restricted CFTR-function and total exocrine tissue defect during pancreatitis remains less known and animal models do not translate well to human disease. To overcome this challenge, we developed a robust and highly durable iPSC-derived model system of pancreatic ductal tissues from an idiopathic pancreatitis patient with a common pancreatitis-associated CFTR variant. In the patient line termed PANx, we found deficient CFTR function and a distinct gene expression signature for ductal tissue pancreatitis marked by aberrant mucin production, inflammatory cytokines and cystic neoplasms. By applying clinically used CFTR-modulator drug ivacaftor, we observed a remarkable restoration of deficient CFTR-mediated fluid secretion as well as upto 40% reversal of the differential gene signature for PANx including the reduction in mucinous neoplasms and immunogenic cytokines such as IL-11, CCL20 and CXCL8. We further employed a microsystem device to model hyperamylasemia, a diagnostic feature of acute pancreatitis attack, due to a ductal reaction causing acinar injury. The key mucinous signature was validated in primary pancreatitis ductal tissues with a CFTR variant. Overall, we unraveled new layers of CFTR-related pathology in pancreatitis to help us better understand the early course of this debilitating condition. The test methods and model systems discovered in this study will significantly expedite the discovery of diagnostic and therapeutic tools for treating idiopathic pancreatitis. For the first time, we provided molecular and physiologic evidence supporting the benefit of CFTR modulator drug ivacaftor in human CFTR-related pancreatitis.

pathology↗

bioRxiv2025

Molecular Regulation and Physiological Role of 1 GOLPH3-mediated Golgi retention

The Golgi complex serves as the central hub of the biosynthetic pathway, where anterograde and retrograde trafficking converge. How cargo and Golgi-resident proteins traverse this organelle has long been debated. Recent studies have identified a molecular machinery that sorts resident proteins into retrograde-directed COPI vesicles during cisternal maturation. Golgi phosphoprotein 3 (GOLPH3) is a key component of this system; however, its physiological relevance and regulatory mechanisms remain poorly defined. Here, we show that GOLPH3 depletion in mice disrupts both protein and lipid glycosylation, causes partially penetrant embryonic lethality, and severely impairs growth and bone mineralization. At the molecular level, we find that GOLPH3 is regulated by functionally antagonistic S-acylation events that control the topology of its membrane association. To mediate retrograde trafficking of Golgi-resident glycosyltransferases, GOLPH3 must bind their cytosolic tails. This occurs via a negatively charged surface region, which is correctly oriented only in one of the S-acylated GOLPH3 conformations. Together, these findings reveal a lipid-mediated regulatory mechanism for intra-Golgi trafficking and establish the critical role of GOLPH3 in vertebrate development.

cell biology↗

bioRxiv2025

Characterizing behavioral and physiological changes in threespine stickleback (Gasterosteus aculeatus) with changing thermal regimes in the Canadian Pacific west coast

Understanding the impacts of sea temperature changes on marine fishes physiology and behavior is critical for marine ecosystem management. Around Vancouver Island, threespine stickleback (Gasterosteus aculeatus) populations thrive in areas that differ by {+/-} 10{degrees}C. To understand the acclimatory potential of stickleback, fish were exposed to cold (10{degrees}C), control (15{degrees}C), or warm (20{degrees}C) water treatments for 4 weeks. Their acclimation response was tested using the novel tank test (NTT), black-white test (BWT), measuring growth, determining critical thermal maxima (CTmax), and measuring heat shock proteins (HSPs). We found that CTmax differed significantly between treatments, however, the increase in acclimation temperature was not proportional to the increase in CTmax. In the BWT, the average number of crosses and duration that fish spent in the white zone was lower in the cold treatment than the control, while these metrics were higher in the warm treatment. A similar trend was observed in the NTT test, with warm treatment having the highest number of crosses and duration in the top third of the tank, and the cold treatment having the lowest. Surprisingly, fish in the cold treatment had a significantly greater change in weight and lowest HSP content than fish kept in the other treatments, which may be associated with energy expenditure and trade-offs for activity. Given these results, greater trade-offs in fish energy usage are anticipated in changing climates due to the acclimation limits of their bodies which would starkly affect ecosystem dynamics. HIGHLIGHTSO_LIClimate change is driving variability in habitats thermal regimes directly impacting the function and performance of animals. C_LIO_LIBehavioral changes (in anxiety or anti-predatory and exploratory behaviors) ensue under changing thermal environments. C_LIO_LIStickleback are reaching the ends of their acclimatory capacity under current peak summer water temperatures. C_LIO_LIConsequences are anticipated with continued warming through trade-offs among energetically expensive processes like behavior, growth, and stress response. C_LI

ecology↗

bioRxiv2025

Early seed priming with closely related Bacillus strains induces divergent physiological and defense responses in melon

Early microbial seed priming is a promising strategy to improve crop resilience, yet it remains unclear whether plants can discriminate among closely related beneficial strains and integrate dose-dependent microbial cues. We primed melon (Cucumis melo) seeds with two phylogenetically similar Bacillus strains (B. subtilis NCIB3610 and B. velezensis FZB42) and combined transcriptomic, metabolomic and physiological analyses across development. Despite comparable colonization, the strains provoked contrasting host programs and distinct dose responses. B. subtilis promoted radicle elongation, chloroplastic starch storage and drought tolerance irrespective of inoculum level, together with L-tryptophan and palatinose accumulation. By contrast, B. velezensis displayed a clear dose effect: low inoculum sustained normal radicle growth, whereas high inoculum transiently repressed it, coinciding with retrotransposon activation, suppression of AOS and proteasome genes, and enrichment of flavonoids and glutathione in leaves. Chemical assays showed that radicle inhibition requires the combination of surfactin, produced by both strains, with bacillomycin D, an iturin-type lipopeptide unique to FZB42; neither molecule alone reproduced the effect. This synergy links the strain-specific lipopeptide repertoire to the dose-dependent growth response. Although their early trajectories diverged, both primings converged on improved above-ground performance. 3610-primed plants restricted Botrytis cinerea via caffeic- and rosmarinic-acid accumulation, whereas FZB42-primed plants curtailed jasmonate-sensitive Tetranychus urticae mites through early JA-pathway activation. Our results demonstrate that melon perceives inoculum dose and microbial identity, translating them into distinct metabolic and defense programs that converge on stress resilience. These mechanistic insights-linking lipopeptide fingerprints, sentinel metabolites and defense transcripts-provide a framework for precision seed treatments in horticultural crops.

plant biology↗

bioRxiv2025

Behavioural and physiological evidence for the development of cardiac-exteroceptive integration during the first year of life

Continuous integration of environmental exteroceptive and internal interoceptive signals is fundamental for perception and adaptive behaviours, yet its developmental trajectory remains poorly understood. Here, we introduced a modified iBEATs paradigm, based on prior work, to investigate cardiac-exteroceptive integration in 3-8-month-old infants. Using behavioural measures of looking time and physiological measures of pupillometry, we found that the ability to detect cardiac-exteroceptive synchrony emerges during the first year of life. Critically, this was evident only when stimuli coincided with systole, the baroreceptor-active phase of the cardiac cycle, supporting central multimodal integration interpretable within a predictive coding framework. Furthermore, individual differences in behavioural sensitivity were accounted for by the degree of autonomic maturation. These findings provide the first evidence for the developmental emergence and mechanisms of cardiac-exteroceptive integration, and establish the modified iBEATs paradigm as a promising tool for assessing interoceptive development in early life.

neuroscience↗

bioRxiv2025

Physiological Reconstitution of Microtubule Doublets

The formation of microtubule doublets (MTDs) is a foundational step in cilia biogenesis, yet how B-tubule nucleation is initiated at the molecular level remains elusive. Here, we identify FAP53 as a crucial factor that promotes B-tubule assembly. Molecular dynamics simulations revealed that FAP53 alleviates steric hindrance from the -tubulin C-terminal tail and stabilizes B-tubule docking at the A-tubule surface. In vitro reconstitution demonstrated that recombinant FAP53 is sufficient to drive MTD formation under physiological tubulin conditions. In cultured HeLa cells, co-expression of CFAP53 and CFAP20--an inner junction protein--induced ectopic MTD-like structures in the cytoplasm. Furthermore, a structurally homologous protein in C. elegans, WFAP-53, localized to sensory cilia; however, when overexpressed, it triggered ectopic MTD formation in neuronal dendrites and concomitantly led to sensory cilia disassembly. These findings uncover a conserved mechanism of B-tubule initiation and underscore the necessity for spatially restricted expression of MTD assembly factors during ciliogenesis.

cell biology↗

bioRxiv2025

Specific Combinations of Physiological Tau Phosphorylation Regulate Tau-Microtubule Interactions in Developing Neurons

Tau phosphorylation is a defining feature of Alzheimers disease, yet it also plays an important physiological role in regulating functional interactions with microtubules (MTs), particularly during normal neuronal development. While individual tau phosphorylation sites have been well-studied, how combinatorial phosphorylation impacts taus behavior in both contexts is poorly understood. We hypothesized that contrasting developmental and pathological models of tau phosphorylation would yield insights into mechanisms of impaired neuronal resilience in tauopathies. We use transgenic PS19 tau mice to demonstrate that increases in individual tau phospho-epitopes with aging do not correlate with their enrichment in tau aggregates in these mice. Using seeded aggregation of tau in neurons, we observe that tau aggregate formation does not necessarily result in MT destabilization; instead, aggregation diminishes taus ability to counteract destabilization when MTs are externally perturbed. We identify that combinations of tau phospho-signatures are responsive to MT destabilization, and phosphorylation at residues S235 and S262 as particularly critical for regulation of interactions with MTs. Phosphorylation of these residues was associated both with significantly reduced binding to MTs, as well as impaired phosphatase response in aggregates. As a whole, this work provides mechanistic insight into phospho-regulation of tau function and prompts reconsideration of the canonical view that tau phosphorylation precedes MT destabilization in disease. Rather, we provide compelling evidence that phosphorylation of tau may be a response to changes in MT stability and that cell death may result from aggregated taus inability to function in this manner. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=162 SRC="FIGDIR/small/669485v2_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@dd84e5org.highwire.dtl.DTLVardef@14001eaorg.highwire.dtl.DTLVardef@13db7a0org.highwire.dtl.DTLVardef@e26d16_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGRAPHICAL ABSTRACTC_FLOATNO Schematic model of our findings: Tau phosphorylation is dynamically regulated in specific combinatorial patterns in response to shifting MT growth cycles. C_FIG

neuroscience↗

bioRxiv2025

Normative neural and physiological correlates of parent-child observational threat extinction

The dyadic relationship between a parent and child is a critical facilitator of social learning, particularly in the management of fear. Vicarious extinction, the process of learning by observing a parent extinguish learned threat responses, holds critical translational potential in understanding adolescent psychopathology involving aberrant threat responses. However, normative biological profiles of vicarious extinction have yet to be uncovered. Here, a community sample of 97 parent-child dyads, enriched for trauma-exposure, completed a validated vicarious extinction paradigm. Youth completed all phases during functional magnetic resonance imaging, while caregivers simultaneously completed the behavioral task. Linear models interrogating normative behavioral, physiological, and neural correlates of acquisition and direct and vicarious extinction, controlled for trauma and symptom severity. The degree of parent-child autonomic synchrony was used to predict the strength of extinction learning. Youth behavioral and skin conductance response markers suggest successful threat acquisition and direct and vicarious extinction. Autonomic arousal during active vicarious extinction learning processes was significantly associated with the strength of parent-child synchrony. Neural activation analyses reveal patterns of early encoding of threat and safety discrimination that were reactivated during later threat reinstatement. Finally, results corroborate and expand known models of direct and vicarious extinction, respectively involving the ventromedial and ventrolateral prefrontal cortex. Altogether, this data confirms that youth can directly and vicariously modify learned threat associations with distinct neurobiological profiles. This delineation of vicarious extinction neural circuitry within a normative population is pivotal for understanding how these processes may be altered by the environment and/or psychopathology during adolescence.

neuroscience↗