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neuroscience: explore 57 source-linked works published from 2026 to 2026, with original documents and citations.

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Includes records with this source-supplied label or an explicit phrase match in their metadata. Matches indicate a mention, not proof that a paper uses a method or tests a material. Source versions are consolidated by DOI.

Sources: biorxiv. Collection updated 2026-09-15. Counts describe this index, not the complete source archives.

bioRxiv2026

Profiling and modulating astrocyte borders at injected biomaterials in mice

Astrocyte border formation is a conserved neuroprotective response to neural tissue disruption, yet astrocyte border states at implanted biomaterials remain less well characterized than injury responses. Here, we developed the Astrocyte Border Characterization (ABC) Tool, which leverages a shear-thinning, injectable biomaterial to locally deliver astrocyte-specific RiboTag AAVs and small molecule regulators in the mouse striatum, enabling molecular profiling and phenotypic modulation of astrocyte border (AB) cells. Spatially precise delivery of AAV using the ABC Tool yielded enhanced specificity and robust RiboTag expression in AB cells from 7-70 days post injection. Temporal transcriptomic profiling of AB cells revealed predominantly acute, transient changes in genes governing dedifferentiation, proliferation, metabolic reprogramming, and inflammation regulation. Persistent changes accounted for only 14% of regulated genes but involved critical gain of functions in immune regulation and host defense that mirrored astrocyte border responses at chronic CNS injuries. Local delivery of indiscriminate or astrocyte-selective ablation molecules delayed, rather than prevented, border formation, ultimately yielding thicker astrocytes borders with increased inflammation and fibrosis at the biomaterial-tissue interface. Conversely, local delivery of {beta}-hydroxybutyrate (BHB) from the ABC Tool altered key aspects of the transcriptional reprogramming to attenuate chronic astrocyte reactivity and prevent biomaterial contraction without exacerbating inflammation or fibrosis. Our findings establish the ABC Tool as a bioassay for studying and manipulating astrocyte borders at implanted biomaterials and identify focal metabolic regulation as a strategy to modulate AB cell phenotypes and enhance the CNS biocompatibility of biomaterials.

neuroscience↗
bioRxiv2026

Test-Retest Reliability of Motor Evoked Potentials Across Eight Bilateral Lower-Limb Muscles

Objectives: Transcranial magnetic stimulation (TMS) is widely used to probe corticospinal excitability by eliciting motor evoked potential (MEP)s in targeted muscles, with MEP characteristics such as magnitude and latency reflecting the physiological state of the pathways being stimulated. Although numerous studies have examined MEP reliability in upper extremity muscles, less is known about the reliability of this measurement across the lower extremity. We hypothesized that inter-session, test-retest reliability of MEPs recorded simultaneously from multiple lower-limb muscles, from a single TMS location, would differ by muscle, stimulation intensity, and quantification method. Materials and Methods: Ten healthy participants (5 males, 5 females) completed three TMS sessions separated by atleast one week. At each session, the stimulation hotspot was identified using a five-location virtual grid anchored at the vertex, with electromyography (EMG) recorded from all eight muscles of interest at each grid location; the grid location producing the largest and most consistent MEPs in the tibialis anterior (TA), the primary target muscle, was selected as the stimulation site and held constant across all three sessions. MEPs were then recorded bilaterally from the TA, soleus, rectus femoris, and biceps femoris muscles at two stimulation intensities (110% and 120% resting motor threshold (RMT)). MEP size was quantified using mean rectified magnitude and peak-to-peak amplitude, and inter-session reliability was assessed using intraclass correlation coefficients (ICC). Bland-Altman analysis was used to characterize the range of measurement variability across all eight muscles. Results: MEP size differed across sessions, and reliability varied by muscle, intensity, and quantification method. The highest reliability was observed in the right TA, the muscle used to establish the stimulation hotspot, using mean rectified magnitude at 120% RMT. Reliability was comparatively lower in the seven non-target muscles recorded from the same fixed stimulation site, indicating that MEP consistency was not uniform across the lower-limb musculature. Conclusions: MEP reliability in the lower extremity depends heavily on the muscle, stimulation intensity, and quantification method used, and is highest in the muscle for which the stimulation site was optimized. These findings support the interpretation that coil positioning targeted to a specific muscle yields more consistent responses in that muscle than in others recorded from the same fixed site, and underscore the importance of careful muscle selection and hotspot optimization when designing TMS protocols for longitudinal or clinical lower-limb research.

neuroscience↗
bioRxiv2026

Multidimensional diffusion MRI reveals heterogeneous microstructural remodeling associated with amyloid pathology

Alzheimer's disease (AD) pathology involves amyloid deposition, reactive gliosis, and localized tissue alterations that coexist within the same brain regions, creating heterogeneous microstructural environments within individual imaging voxels. Conventional diffusion MRI averages these environments into aggregate measures, potentially obscuring their distinct contributions. Frequency-dependent multidimensional MRI ({omega}MD-MRI) resolves distributions of water components with different diffusion length scales, anisotropies, and relaxation properties, providing sensitivity to microstructural restriction, heterogeneity, and shape-size correlations within a voxel. Whether these measurements reveal microstructural complexity associated with AD pathology remains unclear. Here, we performed {omega}MD-MRI on ex vivo brain specimens from approximately 8-month-old 5xFAD and wild-type mice and interpreted the imaging findings alongside complementary histology. {omega}MD-MRI revealed widespread but spatially nonuniform differences between 5xFAD and wild-type brains. Measurements sensitive to microstructural restriction, heterogeneity, and shape-size correlations consistently indicated greater microstructural heterogeneity in 5xFAD brains, with the most prominent differences in the hippocampal formation and major cerebral white matter tracts. Complementary qualitative histology demonstrated extensive amyloid deposition and glial activation in affected regions, while overall cytoarchitecture and myelin organization remained largely preserved. Thus, the {omega}MD-MRI abnormalities occurred in tissue characterized by multiple coexisting pathological and relatively preserved microstructural environments rather than widespread structural degeneration. These findings demonstrate that {omega}MD-MRI can reveal the spatial and microstructural heterogeneity associated with amyloid pathology and provide a more comprehensive characterization of AD-related tissue alterations.

neuroscience↗
bioRxiv2026

Development and pharmacological evaluation of an intranasal liposomal norbinaltorphimine formulation for the prevention of pain-induced negative affect

Chronic pain is frequently accompanied by negative affect and motivational deficits due to dysregulated mesocorticolimbic dopamine and kappa opioid receptor (KOR) signalling. Although intracranial KOR antagonism prevents pain-induced negative affect in preclinical models, systemic KOR antagonists can produce adverse off-target effects in the periphery, thereby limiting its clinical utility. Consistent with this, we found that systemic administration of KOR antagonist norbinaltorphimine (NorBNI), exacerbated motivational deficits in rats with persistent inflammatory pain. We hypothesized that maximizing central and minimizing peripheral KOR antagonism could overcome these limitations. To test this, we engineered an intranasal liposomal NorBNI formulation incorporated into an in-situ forming mucoadhesive hydrogel to enable selective nose-to-brain delivery (Nor-BNILV-HG). We characterized its physicochemical properties and functional efficacy in rats with inflammatory pain produced by Complete Freund's Adjuvant (CFA). NorBNI-loaded liposomes exhibited high drug entrapment efficiency, nanometric size, and suitable surface charge for intranasal administration. The selected thermosensitive hydrogel demonstrated appropriate gelation properties and sustained drug release. Intranasal administration of NorBNI-LV-HG produced negligible systemic NorBNI levels compared with intraperitoneal delivery. In vivo microdialysis showed that NorBNI-LV-HG prevented KOR agonist-induced reductions in nucleus accumbens (NAc) dopamine release, confirming functional central KOR blockade. Behaviourally, intranasal NorBNI-LV-HG attenuated pain-induced impairments in sucrose motivation. Importantly, unlike systemic NorBNI, repeated intranasal NorBNI-LV-HG did not alter mechanical nociceptive thresholds in pain-naive animals, suggesting this strategy mitigates unwanted peripheral nociceptive effects. Together, these findings demonstrate that intranasal NorBNI-LV-HG achieves functional brain KOR antagonism while minimizing systemic exposure and off-target effects. Selective nose-to-brain delivery of KOR antagonists therefore represents a promising therapeutic strategy to prevent and potentially reverse the affective and motivational consequences of pain and may overcome key translational barriers associated with systemic KOR treatments.

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bioRxiv2026

GABAB Receptors Gate Sex-Specific Synaptic Plasticity in the Nucleus Accumbens

Excitatory synaptic plasticity within the nucleus accumbens (NAc) drives motivated behaviors, and dysregulation is implicated in several psychiatric disorders marked by impaired reward processing. The NAc integrates glutamatergic input, which conveys information about reward, context, and behavioral goals, with local GABAergic signaling that regulates excitatory transmission and medium spiny neuron (MSNs) output. However, little is known regarding GABA-dependent modulation of activity-dependent excitatory synaptic plasticity. Here, we investigated GABAB receptor (GABABR) regulation of plasticity at hippocampus (Hipp)-NAc synapses, at which plasticity is a key mediator of reward-related behaviors. Using whole-cell electrophysiological recordings in mouse brain slices, we found that pharmacological inhibition of GABABRs converts long-term potentiation (LTP) into long-term depression (LTD) selectively in females, identifying a sex-specific role for GABABRs in modulating long-term plasticity of Hipp-MSN synapses. This LTD required mGluR5 activation and estrogen receptor alpha (ER) in both D1- and D2-expressing MSN subtypes, while only D1-MSNs suggested that LTD was expressed presynaptically through a CB1 receptor-dependent mechanism. Notably, GABABR inhibition did not alter basal synaptic transmission, indicating a specific role for these receptors in gating plasticity beyond regulation of basal excitatory drive. Together, these findings identify a novel, sex-specific mechanism by which GABABRs control the direction of synaptic plasticity.

neuroscience↗
bioRxiv2026

MHC class II in dopaminergic neurons prunes GABAergic synapses in neurodevelopmental disorders

Although the brain was traditionally considered immune-privileged, recent studies show immune factors play key roles in brain function. Dysfunction of these factors is linked to neurodevelopmental disorders, but mechanisms remain unclear. Using a maternal immune activation (MIA) mouse model, we investigated immune-related genes in neurodevelopmental disorder pathogenesis. MIA mice showed increased locomotor activity and disrupted prepulse inhibition. RNA-seq and qPCR analyses revealed persistent increases in major histocompatibility complex class II (MHCII) expression and persistent decreases in GABAergic synapse-related gene expression, particularly glutamate decarboxylase (Gad) expression, in dopaminergic regions. These expressions were negatively correlated, and immunohistochemistry showed MHCII at postsynaptic GABAergic synapses on dopaminergic neurons. Patch-clamp recordings confirmed reduced mIPSC frequency in MIA mice. MHCII knockout mice showed opposite phenotypes, while MHCII overexpression in dopaminergic neurons decreased Gad expression. These results suggest MIA-induced MHCII upregulation enhances pruning of GABAergic synapses on dopaminergic neurons, leading to behavioral deficits.

neuroscience↗
bioRxiv2026

Neural spiketrains and population vectors entangle neural representations

Neural recordings are usually analyzed by comparing neural spiketrains or comparing time bins (population vectors). If multiple variables drive the neural activity these comparisons will be affected by all of them. Our aim is to disentangle these different latent variables or covariates that drive neural activity and reveal their structure and geometry. The central idea of the paper is that a matrix is disentangled when its rows and columns are local on each other, a condition we call bidirectional locality. In such a matrix, rows and columns encode the same geometry and they respond to only one localized part of it. This suggests finding bidirectional local matrices in a given data matrix, from which we can recover the geometry of the covariates driving it in a straightforward way. We present two ways of doing just this. The first method, coherent projections, works by finding non-negative projections of the neural data matrix (neurons by time bins) that are bidirectionally local. The second method, clumps, works by finding dense submatrices of the neural data matrix, that each identify a local region of one covariate. We apply these methods to two neural datasets, showing that they can separate grid cell modules and reveal a movement-driven low-dimensional structure in the motor cortex.

neuroscience↗
bioRxiv2026

Dysregulated splenic glucocorticoid sensitivity in aging and an α-synuclein transgenic mouse model of Parkinson's disease

Introduction: Parkinson's disease (PD) and aging both disrupt hypothalamic-pituitary-adrenal (HPA) axis function and peripheral immune homeostasis. Whether aging or -synuclein (-syn) pathology alters glucocorticoid (GC) sensitivity of peripheral immune cells has not been investigated. Methods: Using an ex vivo GC sensitivity assay, we assessed the responsiveness of isolated and lipopolysaccharide (LPS)-stimulated splenocytes to the anti-inflammatory effects of increasing doses of corticosterone (CORT) in a wild-type (WT) aging cohort and in a PD -syn transgenic mouse model and respective age-matched controls. Results: Compared with splenocytes from 6-month-old WT mice, splenocytes from 20-month-old WT mice were less sensitive to 0.1 and 0.5 M CORT. Isolated splenocytes from PD vs. control mice were less sensitive to 0.05, 0.1, and 0.5 M CORT specifically at 16 months of age, but not at 6 or 20 months of age. As peripheral immune phenotyping revealed neither differences in HPA axis-related parameters nor in splenic GC receptor expression between PD and age-matched control mice at 6, 16, and 20 months, splenic GC resistance in PD mice at 16 months of age seems to be mediated by downstream GR signaling dysfunction. Conclusion: Together, our results support the hypothesis that -syn pathology accelerates an aging-associated decline in the peripheral sensitivity to anti-inflammatory GCs and may thereby sustain systemic and neuroinflammatory processes in PD.

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bioRxiv2026

Spacing theta-burst stimulation enhances synaptic potentiation in the vulnerable prefrontal cortex

Neuromodulation with intermittent theta-burst stimulation (iTBS) is a clinical treatment for major depression. One postulated mechanism of iTBS is to strengthen the synaptic connections which activate the prefrontal cortex to regulate mood. With ex vivo electrical stimulation and neuronal calcium imaging, we demonstrate that a common, clinical iTBS pattern (600-stimuli, ~3-min) reliably strengthens the synaptic recruitment of the adult mouse prefrontal cortex. This synaptic potentiation, however, becomes less reliable in the depressive-like mouse model of prolonged social isolation. Examining the complex calcium elevations during clinical iTBS reveals that the induction peaks rise higher in social isolation but no longer predict the synaptic potentiation outcome. To better regulate calcium dynamics during induction, we test a paradigm with fewer iTBS episodes, separated by longer intervals. This spaced iTBS (90-stimuli, ~10-min) in the adult prefrontal cortex limits calcium elevation during induction and yields greater long-term potentiation (LTP) following either juvenile- or adult-onset social isolation. This research illustrates new strategies to interrogate and to enhance synaptic plasticity in the vulnerable prefrontal cortex.

neuroscience↗
bioRxiv2026

Sensory neuron dysfunction and hyperexcitability in dorsal root ganglia at disease onset in the SOD1G93A mouse model of ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder traditionally characterized by motor neuron degeneration, but emerging evidence indicates sensory system involvement. Despite reports of sensory abnormalities in some patients, the molecular and functional alterations in dorsal root ganglion (DRG) neurons remain insufficiently characterized. We investigated DRG pathology at disease onset in 12-week-old SOD1G93A mice using an integrated transcriptomic, morphological, and electrophysiological approach. RNA sequencing of lumbar DRG identified 35 differentially expressed genes, predominantly upregulated, enriched in oxidative stress-related and phagosome pathways. Comparative analysis with motor neuron transcriptomes revealed distinct gene expression profiles, indicating sensory neuron-specific molecular responses. Immunohistochemistry demonstrated reduced soma diameter in both A- and C-fiber DRG neurons. Nav channel colocalization increased for Nav1.7 in A fibers and Nav1.8 in both fiber types, whereas Nav1.6 was unchanged. Whole-cell patch-clamp recordings showed depolarized resting membrane potential, increased spike amplitude, and enhanced repetitive firing in A-fiber neurons, consistent with hyperexcitability, while C fibers showed no significant functional changes. These findings demonstrate early molecular, structural, and functional alterations in primary sensory neurons in ALS, supporting pathology beyond motor neurons and identifying sensory neuron excitability as a potential therapeutic target.

neuroscience↗
bioRxiv2026

Hypothermic Conditions Impair GnRH Pulse Generator Activity and Gametogenesis

Mammalian reproductive function is driven by arcuate kisspeptin neurons, pacemakers of gonadotropin secretion. During energy shortages, animals reallocate resources from reproduction to survival; however, the underlying neural mechanisms remain elusive. Here we used fiber photometry to chronically monitor synchronized episodes of arcuate kisspeptin neuron activity (SEskiss) in adult mice under various energy-saving conditions. In both sexes, SEskiss frequency was markedly suppressed during fasting-induced torpor and pharmacologically induced hypothermia, whereas hypometabolism alone had no discernible effect. A Q neuron-induced hypothermic state (QIH) robustly suppressed SEskiss, leading to impaired gamete maturation, whereas warming the body temperature during QIH fully restored SEskiss frequency. These findings demonstrate that hypothermia, rather than hypometabolism, is the primary driver of suppression of the hypothalamic reproductive axis during energy-saving conditions. This study provides insights into how thermal signals act as critical gatekeepers in the mammalian reproductive system.

neuroscience↗
bioRxiv2026

Anxiety-Related Traits Are Associated with Subjective Biases but not Altered Threat-Safety Discrimination

Anxiety-related traits (ARTs) have been linked to altered fear learning, but previous studies have typically examined different experimental phases and response systems, limiting the comparability of findings and the accumulation of consistent evidence. Here, we comprehensively examined associations between ARTs and fear conditioning across acquisition, extinction and renewal and across subjective, physiological and neural response systems in a well-powered sample (N = 267) using a two-day differential conditioning paradigm. ARTs were operationalized as a composite of trait anxiety, neuroticism, and intolerance of uncertainty and conditioned responding was assessed using skin conductance responses, fear-potentiated startle, US expectancy ratings, fear ratings, and functional magnetic resonance imaging. Higher ARTs were consistently associated with elevated subjective fear and US expectancy to both threat and safety cues during extinction and renewal, without corresponding elevations in physiological responding. At the same time, ARTs were not associated with threat-safety discrimination in subjective or physiological measures across phases, while neural associations were limited to reduced dorsal anterior cingulate cortex discrimination during early renewal. These findings suggest that ARTs are characterized by a CS unspecific cognitive bias toward heightened threat expectancy and evaluation rather than altered associative fear learning, highlighting the importance of distinguishing conditioned discrimination from general levels of responding across response systems.

neuroscience↗
bioRxiv2026

Linking continuous behavior to aesthetic enjoyment in a walkable virtual-reality museum tour: effects of agency and a painting-level analysis framework

Museum visits typically follow curator-defined routes that constrain how visitors shape their own experience, yet choice is widely held to heighten engagement, autonomy, and enjoyment. Virtual reality (VR) offers a setting in which to study these processes because it combines ecological immersion with precise, continuous behavioral measurement. We investigated (i) whether VR- derived behavioral signals are associated with self-reported enjoyment during a virtual museum tour, and (ii) whether the level of agency afforded to visitors influences enjoyment. Forty-eight adults completed a room-scale, life-size VR tour (8 * 4 m) of seven paintings from the Tel Aviv Museum of Art, each accompanied by a synchronized audio guide. Synchronized gaze and head- position streams were logged continuously (50 Hz) and segmented into painting-level viewing episodes using a trial-and-tile pipeline that intersects each painting's trial interval with an empirically defined spatial window in front of the canvas. Participants were randomly assigned to one of three agency conditions, Active (choice before every artwork), Semi-Active (choice for the first three), or Passive (fixed route),while the artwork sequence was held identical. Self- reported enjoyment at the tour and painting levels did not differ reliably across agency conditions. Among VR-derived measures, gaze engagement during the audio guide showed the clearest (though modest) association with painting-level liking, whereas locomotion and pacing measures were weak and inconsistent predictors. Agency nonetheless reliably modulated several gaze- and time-based viewing measures. The findings reveal a dissociation between subjective enjoyment and the micro-structure of viewing, and establish a reusable framework for full-tour, painting-level behavioral analysis in immersive settings.

neuroscience↗
bioRxiv2026

Motor planning and execution establish distinct feedforward and feedback motor histories

Movements are systematically affected by the recent motor history. These history effects may be induced either by reused motor plans or from lingering tuning of the previous movements' execution. We dissociated planning and execution using four experimental manipulations across two complementary motor paradigms. We isolated planning by preventing execution with stop signals and mechanical blocks, and execution by moving participants' hand passively using a robot manipulandum. History effects emerged in feedforward movement aspects - reaction time and early movement kinematics - following isolated planning. In contrast, they were absent or markedly reduced for isolated execution. History effects emerged also in late movement aspect that involves sensory feedback during execution - movement accuracy and precision - but only when movements were both planned and executed. Feedforward effects generalized across hands, whereas feedback effects were effector specific. Thus, prior motor planning and execution make distinct and complementary contributions in shaping future motor behavior.

neuroscience↗
bioRxiv2026

Feature-based valuation and its impairment in people with compulsive and addictive symptoms

Effective decision-making requires evaluating options based on relevant features while reducing attention to those that are not. However, how attention prioritizes one source of information over another during value-based decisions remains unknown. Across 7 experiments, we show that irrelevant features both constructively and destructively interfered with how values are assigned to choice options. When relevant and irrelevant features agreed, choice accuracy and speed were facilitated; when they conflicted, accuracy decreased and choices slowed in proportion to the value of the irrelevant feature. We modeled this interference as a weighted sum of relevant and irrelevant feature values. This model explained individual differences in choice behavior and, critically, tracked psychiatric symptom severity related to substance abuse and obsessive-compulsive disorder. This suggests that these symptoms may, in part, reflect an impaired ability to weigh relevant against irrelevant information when assigning value to choice options - a process we term feature-based valuation.

neuroscience↗
bioRxiv2026

Hyperglycemia Activates Retinal Photoreceptors to Induce Neuroglial Inflammation

Abstract Diabetic retinopathy (DR) is a major cause of vision loss in working-age adults. Accumulating evidence suggests that retinal photoreceptors contribute to the initiation and progression of diabetic retinopathy. In this study, we investigated whether hyperglycemia directly alters photoreceptor signaling and whether photoreceptor-derived inflammatory mediators activate downstream Muller glial cells. Primary photoreceptors were isolated from adult mice and cultured with normal glucose, high D-glucose, or high L-glucose as an osmotic control. Photoreceptorconditioned media were analyzed for inflammatory and growth factors and used to stimulate primary Muller glia. High glucose exposure increased photoreceptor production of TNF-a, IL-6, and VEGF. Photoreceptorconditioned media from high glucose-treated photoreceptors induced Muller glial expression of IL-1b, TNF-a, and IL-6. Muller glia exposed to photoreceptor-conditioned media increased VEGF expression and secretion and enhanced MMP-9 expression, secretion, and gelatinase activity. Together, these findings support a direct role for photoreceptors as glucose-responsive neuronal cells that can initiate and amplify neuroglial inflammatory signaling in hyperglycemic conditions.

neuroscience↗
bioRxiv2026

A transcriptomic and spatial map of serotonin autoreceptor expression in Drosophila

Serotonin is an evolutionarily ancient neurotransmitter that modulates an array of behaviors such as mood, sleep, and appetite across species. Serotonin acts primarily by binding to serotonin receptors, which are expressed in post-synaptic neurons (heteroreceptors) and serotonergic neurons themselves (autoreceptors). Serotonin autoreceptors modulate serotonergic tone, the foundational principles of which have been excellently demonstrated in vertebrate and invertebrate models. However, many aspects of the mechanisms and contexts in which this modulation occurs are still unclear. Drosophila melanogaster is a powerful model organism that can provide unique insights into autoreceptor function by the ability to perform precise spatial and temporal genetic manipulation with structural and functional readouts / behaviors of serotonin systems. However, a systematic characterization of serotonin autoreceptor expression in Drosophila has not been conducted. Here we use single-cell sequencing and genetic labeling to show that all five serotonin receptors are expressed in serotonergic neurons and map their expression at both the larval and adult stages of development. This is the first evidence of 5-HT2A and 5-HT7 expression in serotonergic neurons in any organism. Moreover, the unique combinations of autoreceptor expression in specific neuronal clusters will aid in the development of novel hypotheses for autoreceptor function, and demonstrates the utility of Drosophila as a model organism to study the function of serotonin autoreceptors.

neuroscience↗
bioRxiv2026

VDAC1 regulates stress-associated matrix localization of DJ-1 to support mitochondrial homeostasis and neuronal survival

DJ-1 is a redox-sensitive protein implicated in early-onset Parkinson's disease, and its mitochondrial localization protects against oxidative stress, but the mechanisms regulating its submitochondrial targeting and functional impact on mitochondrial integrity remain poorly understood. We identify voltage-dependent anion channel 1 (VDAC1) as a regulator of the submitochondrial distribution of DJ-1 during stress. Endogenous DJ-1 interacted with VDAC1, and loss of VDAC1 reduced stress-induced DJ-1 accumulation within the mitochondrial matrix. VDAC1-deficient neurons exhibited mitochondrial fragmentation, impaired oxidative phosphorylation, reduced ATP levels, altered reactive oxygen species (ROS) responses, and increased sensitivity to MPP+;. Matrix-targeted, but not outer-membrane-targeted, DJ-1 rescued basal, ATP-linked, and maximal respiration, improved mitochondrial morphology, and enhanced neuronal survival. ATP synthase inhibition also rapidly increased mitochondrial DJ-1, suggesting bioenergetic stress promotes its mitochondrial accumulation. Our findings identify compartment-specific localization as a key determinant of DJ-1 function and establish VDAC1-dependent matrix targeting as a critical mechanism supporting mitochondrial integrity during stress.

neuroscience↗
Compare source metadata on this page
WorkPublishedSource identifierSource
Profiling and modulating astrocyte borders at injected biomaterials in mice2026-09-0110.64898/2026.08.26.747354v1biorxiv
Test-Retest Reliability of Motor Evoked Potentials Across Eight Bilateral Lower-Limb Muscles2026-09-0110.64898/2026.08.26.747367v1biorxiv
Multidimensional diffusion MRI reveals heterogeneous microstructural remodeling associated with amyloid pathology2026-09-0110.64898/2026.08.26.747377v1biorxiv
Development and pharmacological evaluation of an intranasal liposomal norbinaltorphimine formulation for the prevention of pain-induced negative affect2026-09-0110.64898/2026.08.26.747378v1biorxiv
GABAB Receptors Gate Sex-Specific Synaptic Plasticity in the Nucleus Accumbens2026-09-0110.64898/2026.08.26.747391v1biorxiv
MHC class II in dopaminergic neurons prunes GABAergic synapses in neurodevelopmental disorders2026-09-0110.64898/2026.08.26.747425v1biorxiv
Neural spiketrains and population vectors entangle neural representations2026-09-0110.64898/2026.08.27.744867v1biorxiv
Dysregulated splenic glucocorticoid sensitivity in aging and an α-synuclein transgenic mouse model of Parkinson's disease2026-09-0110.64898/2026.08.27.745197v1biorxiv
Spacing theta-burst stimulation enhances synaptic potentiation in the vulnerable prefrontal cortex2026-09-0110.64898/2026.08.27.746330v1biorxiv
Sensory neuron dysfunction and hyperexcitability in dorsal root ganglia at disease onset in the SOD1G93A mouse model of ALS.2026-09-0110.64898/2026.08.27.747263v1biorxiv
Hypothermic Conditions Impair GnRH Pulse Generator Activity and Gametogenesis2026-09-0110.64898/2026.08.27.747452v1biorxiv
Anxiety-Related Traits Are Associated with Subjective Biases but not Altered Threat-Safety Discrimination2026-09-0110.64898/2026.08.27.747474v1biorxiv
Linking continuous behavior to aesthetic enjoyment in a walkable virtual-reality museum tour: effects of agency and a painting-level analysis framework2026-09-0110.64898/2026.08.27.747505v1biorxiv
Motor planning and execution establish distinct feedforward and feedback motor histories2026-09-0110.64898/2026.08.27.747554v1biorxiv
Feature-based valuation and its impairment in people with compulsive and addictive symptoms2026-09-0110.64898/2026.08.27.747558v1biorxiv
Hyperglycemia Activates Retinal Photoreceptors to Induce Neuroglial Inflammation2026-09-0110.64898/2026.08.27.747567v1biorxiv
A transcriptomic and spatial map of serotonin autoreceptor expression in Drosophila2026-09-0110.64898/2026.08.27.747575v1biorxiv
VDAC1 regulates stress-associated matrix localization of DJ-1 to support mitochondrial homeostasis and neuronal survival2026-09-0110.64898/2026.08.27.747597v1biorxiv

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