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neuroscience

neuroscience: explore 87 source-linked works published from 2026 to 2026, with original documents and citations.

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Sources: biorxiv. Collection updated 2026-09-17. Counts describe this index, not the complete source archives.

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↗

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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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-minutes) 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. To better understand this change, we examine the impact of social isolation on the complex pattern of calcium elevation during clinical iTBS. In social isolation, the calcium peaks rise more prominently, but the induction peak no longer predicts 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-minutes) in the adult prefrontal cortex limits calcium elevation during induction and yields reliable 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.

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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.

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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.

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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.

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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↗

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.

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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.

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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.

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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.

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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.

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Parabrachial-amygdala circuit cooperates with a posterior striatal area to drive opioid withdrawal aversion

Opioid addiction treatment is often hampered by the severe dysphoria of opioid withdrawal, but withdrawal treatments are limited by incomplete understanding of brain mechanisms involved. One area frequently implicated in withdrawal symptoms is the central amygdala, whose capsular portion (CeC) is particularly strongly activated during withdrawal. Additionally, a ventral posterior striatal region that resides near CeC, the interstitial nucleus of the posterior limb of the anterior commissure (IPACc), is also activated as strikingly as CeC. However, it is still unknown how these regions are activated, nor whether their activation explains the high intensity of withdrawal dysphoria. Using RNAscope, we found that c-fos expression is induced in the parabrachial nucleus (PB), a key glutamatergic afferent of CeC, after precipitated morphine withdrawal. Chemogenetic inhibition of PB glutamatergic neurons (VG2PB) nearly eliminated withdrawal-induced CeC c-Fos, without affecting IPACc c-Fos, indicating these two nuclei are activated by distinct sources. Furthermore, VG2PB inhibition markedly reduced somatic (jumping) and modestly reduced affective (place avoidance) withdrawal behavior. On the other hand, inhibition of CeC-projecting PB neuronal subtypes expressing calcitonin gene-related peptide (CGRP) or mu opioid receptor (MOR) reduced place avoidance without affecting jumping, indicating their specific role in withdrawal aversion. Strikingly, simultaneous inhibition of VG2PB and posterior striatal region containing IPACc robustly reduced withdrawal-induced place avoidance much more than the modest effects of either inhibition alone, suggesting their cooperative action in driving aversion. Our data suggests that PB-CeC circuit and posterior striatal area constitute a cooperative system driving opioid withdrawal aversion.

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MAPT regulates autophagic-lysosomal function and phagocytosis in human microglia

Tauopathies are characterized by the accumulation and spread of pathogenic tau aggregates throughout the brain, a process that is increasingly recognized to involve not only neurons but also microglia. However, whether pathogenic MAPT directly alters microglial degradative capacity remains poorly understood. Here, using isogenic human induced pluripotent stem cell-derived microglia carrying the pathogenic MAPT IVS10+16 mutation, we identify tau as a regulator of microglial lysosomal function. MAPT IVS10+16 microglia exhibited coordinated suppression of lysosomal and autophagic pathways, reduced lysosomal protease abundance and activity, and impaired autophagosome-lysosome fusion. Mutant microglia also showed reduced uptake of extracellular tau aggregates, reduced tau accumulation in acidic compartments, and a blunted lysosomal response to proteopathic stress. Conversely, genetic loss of MAPT increased lysosomal degradative capacity and accumulation of extracellular tau aggregates within acidic compartments, supporting a cell-intrinsic role for endogenous tau in regulating microglial degradative function. Pharmacologic enhancement of the autophagy lysosome pathway in MAPT IVS10+16 microglia increased proteolytic activity and improved tau handling. Together, these findings reveal a reciprocal relationship between tau and microglial lysosome function and identify degradative capacity as a modifiable component of the microglial response to tau pathology.

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Excessive cholesterol accumulation in microglia increases neuronal synaptic vulnerability to amyloid-beta

Cholesterol efflux is an important determinant of cellular lipid homeostasis. However, how microglial excessive cholesterol accumulation affects neuronal synaptic integrity remains poorly understood, particularly in the context of Alzheimer's disease. Here, we utilized a conditional knockout mouse model targeting the cholesterol transporters ABCA1 and ABCG1 in microglia. The microglia-specific ABCA1/ABCG1 deficiency triggered marked cholesterol accumulation, microglial hypertrophy, downregulation of the homeostatic marker P2ry12, and upregulation of the reactivity-associated marker CD11b, indicating shift toward a reactive phenotype. This phenotype was accompanied by increased reactive oxygen species, consistent with enhanced oxidative stress in ABCA1/ABCG1-deficient microglia compared with control. Using organotypic hippocampal slice cultures, we investigated the downstream neuronal outcomes of microglial ABCA1/ABCG1 deficiency. Under basal conditions, microglial ABCA1/ABCG1 knockdown did not significantly alter dendritic spine density in CA1 pyramidal neurons. However, upon exposure to amyloid-beta (A{beta}) stress, microglial ABCA1/ABCG1 deficiency markedly exacerbated dendritic spine loss in CA1 pyramidal neurons. Taken together, our findings highlight an important role for ABCA1/ABCG1-dependent cholesterol efflux in maintaining microglial homeostasis and limiting neuronal synaptic vulnerability to A{beta}-associated stress. These results support further investigation of microglial cholesterol transport as a potential target for preserving synaptic resilience in Alzheimer's disease.

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Compare source metadata on this page
WorkPublishedSource identifierSource
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
Parabrachial-amygdala circuit cooperates with a posterior striatal area to drive opioid withdrawal aversion2026-09-0110.64898/2026.08.27.747629v1biorxiv
MAPT regulates autophagic-lysosomal function and phagocytosis in human microglia2026-09-0110.64898/2026.08.27.747662v1biorxiv
Excessive cholesterol accumulation in microglia increases neuronal synaptic vulnerability to amyloid-beta2026-09-0110.64898/2026.08.27.747668v1biorxiv

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