Neuroscience[JOURNAL]
Sun
200 papers
Voltage dynamics of cortical dendrites in vivo.
Wong-Campos JD, Park P, Lee BH … +9 more , Davis HC, Qi Y, Tian H, Itkis DG, Kim D, Grimm JB, Plutkis SE, Lavis LD, Cohen AE
Nat Neurosci · 2026 Jun · PMID 42321471 · Publisher ↗
Voltage dynamics in dendrites, which result both from integrating synaptic inputs and back-propagating action potentials (bAPs) from the soma, contribute to plasticity. Mapping these dynamics in the dendritic arbors of l...
Voltage dynamics in dendrites, which result both from integrating synaptic inputs and back-propagating action potentials (bAPs) from the soma, contribute to plasticity. Mapping these dynamics in the dendritic arbors of live animals is crucial for understanding neuronal computation and plasticity rules. Here we combine targeted channelrhodopsin activation with dual-plane structured illumination voltage imaging for simultaneous monitoring of dendritic and somatic voltage response dynamics in cortical layer 2/3 pyramidal neurons in anesthetized and awake mice. We examined the integration of synaptic inputs and compared the dynamics of optogenetically evoked, spontaneous and sensory-evoked subthreshold and bAP dynamics. Our measurements revealed a broadly correlated membrane voltage throughout the dendritic arbor and only weak signatures of electrical compartmentalization within individual dendritic branches. However, we observed strong spiking-history-dependent modulation of bAP propagation into distal dendrites. We propose that this dendritic filtering of bAPs may have a critical role in the regulation of bursting and in activity-dependent plasticity.
Tryptamine from wake-active monoaminergic neurons regulates sleep homeostasis.
Cao H, Wang K, Zhao J … +19 more , Zha ZH, Zhang Q, Xiu Y, Wu B, Huang S, Zhu XN, Li X, Chen J, Wen H, Pan S, Yang KX, Hu J, Yu JT, Liu ZJ, Hua T, Mu Y, Hu Z, Yuan P, Zhang Z
Nat Neurosci · 2026 Jun · PMID 42321470 · Publisher ↗
Wakefulness produces sleep-promoting substances and the cerebrospinal fluid contains substances that reflect homeostatic sleep pressure. However, identities of such molecules, and the neural mechanisms for producing and...
Wakefulness produces sleep-promoting substances and the cerebrospinal fluid contains substances that reflect homeostatic sleep pressure. However, identities of such molecules, and the neural mechanisms for producing and sensing them, remain mysterious. Here we show that cerebrospinal fluid levels of tryptamine (TrpA) track homeostatic sleep pressure in nocturnal mice and diurnal pigs, reflecting physical activity history independently of light-dark cycles. We developed a ratiometric fluorescent sensor for TrpA and showed that TrpA is produced by wake-active monoaminergic nuclei in the diencephalon and brainstem and is secreted in an activity-dependent manner. We showed that released TrpA binds to G-protein-coupled receptor 139 (GPR139) and enhances neuronal excitability in the hypothalamic preoptic area to promote sleep. TrpA-GPR139 signaling was necessary for homeostatic sleep rebound and small-molecule GPR139 agonists promoted sleep duration and quality. Together, our study reveals TrpA as a signal related to sleep homeostasis and GPR139 as a druggable target against its disruption.
A fatty acid amide activates myeloid cells and improves neurovascular outcomes in retinal degeneration.
Wei G, Chatterjee S, Yang Q … +18 more , Vijayakumar S, Ogasawara D, Giles S, Biscocho K, Westenskow P, Wang J, Fan R, Pham H, Aguilar E, Robinson J, Usui-Ouchi A, Bonelli R, Eade K, Siuzdak G, Cravatt B, Sailor MJ, Boger D, Friedlander M
Nat Neurosci · 2026 Jun · PMID 42321469 · Publisher ↗
Neurovasculoglial cross-talk underlying breakdown of the neurovascular unit is a central, yet poorly understood, component of many neurodegenerative disorders of the CNS, including retinal disease. Primary fatty acid ami...
Neurovasculoglial cross-talk underlying breakdown of the neurovascular unit is a central, yet poorly understood, component of many neurodegenerative disorders of the CNS, including retinal disease. Primary fatty acid amides have been identified to regulate this cross-talk between vasculature and neuronal tissues, but specific molecules and mechanisms remain unresolved. Here we show, using an unbiased high-resolution metabolomics screen, that erucamide, a 22:1 monounsaturated omega-9 fatty acid amide, is highly dysregulated during photoreceptor degeneration in mice. In vivo delivery of erucamide using organosilane-modified porous silicon nanoparticles activated retinal myeloid cells, leading to the upregulation of angiogenic and neurotrophic cytokines that limited vascular and neuronal degeneration. We identified TMEM19 as a binding protein for erucamide that is crucial for myeloid cell activation and subsequent neuroprotection. These findings reveal a previously unknown primary fatty acid amide pathway that modulates neuroimmune interactions during retinal degenerative diseases. We propose erucamide and analogs as candidate therapeutics.
Molecular crosstalk between MAPK signaling and neuroprotective pathways in Parkinson's disease: from pathogenesis to therapeutic potential.
Shalabi MG, Al-Kuraishy HM, Shokr MM … +1 more , Batiha GE
Neuroscience · 2026 Jun · PMID 42320726 · Publisher ↗
Mitogen-activated protein kinase (MAPK) signaling is increasingly recognized as a central regulator in the pathogenesis of Parkinson's disease (PD). PD is a chronic neurodegenerative disorder characterized by the progres...
Mitogen-activated protein kinase (MAPK) signaling is increasingly recognized as a central regulator in the pathogenesis of Parkinson's disease (PD). PD is a chronic neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), driven by a complex interplay of mitochondrial dysfunction, oxidative stress, and neuroinflammation. While basal MAPK activity is essential for neuroprotection and neuronal growth, its overactivation, specifically via the JNK and p38 cascades, accelerates neurodegeneration. This review explores the molecular landscape of MAPK signaling, detailing how its dysregulation promotes the accumulation of alpha-synuclein and the activation of microglia. Furthermore, it highlights critical crosstalk between MAPK and other vital pathways, including the inhibition of the neuroprotective PI3K/AKT and PP2A pathways and the detrimental activation of GSK-3β and PTEN signaling. Preclinical evidence strongly supports the use of MAPK inhibitors to mitigate dopaminergic neurotoxicity and reduce proinflammatory cytokine release. Despite promising results in experimental models and the development of highly selective inhibitors, clinical translation remains challenging due to potential systemic toxicities. This manuscript provides a comprehensive synthesis of mounting and mooting evidence, positioning MAPK inhibition as a potent, albeit complex, adjuvant strategy for delaying the onset and progression of PD neuropathology.
BDNF-modulated plastic changes to dendritic spines in the hippocampus and prefrontal cortex underlie the NMDA-induced pre-convulsive stereotyped behavior in rats.
Hernández-González M, Barrera-Cobos FJ, Guevara MA … +3 more , González-González D, Flores-Soto M, González-Burgos I
Neuroscience · 2026 Jun · PMID 42320725 · Publisher ↗
Systemic administration of NMDA induces stereotyped behavior followed frequently, but not always, by generalized epileptiform seizures. Increased NMDA activity provokes overstimulation of NMDA glutamate receptors in neur...
Systemic administration of NMDA induces stereotyped behavior followed frequently, but not always, by generalized epileptiform seizures. Increased NMDA activity provokes overstimulation of NMDA glutamate receptors in neurons with dendritic spines. Systemic administration of 100 mg/kg of NMDA i.p. induced stereotyped behavior in adult male rats 5-10 min post-injection. Then, the density and proportion of the various types of spines were counted in pyramidal neurons of the hippocampus and prefrontal cortex of two groups: NMDA-treated rats and a Saline control. Dendritic spine density increased in the experimental rats in both study regions, manifested in a higher proportion of stubby and wide (neckless) types. This type of spine showed a significant interaction between groups and brain structures. No changes were observed in the thin or mushroom spines. BDNF increased in the prefrontal cortex but remained unchanged in the hippocampus, suggesting that differential modulatory BDNF-mediated mechanisms are involved in synaptic plasticity in these two brain areas. The predominance of neckless (stubby, wide) spines suggests their involvement in synaptic overstimulation in both the hippocampus and prefrontal cortex. This possibility requires further research using diverse methodologies. This is the first study of the synaptic plasticity -mediated by dendritic spines- that underlie the pre-convulsive, stereotyped behavior in an experimental model based on epileptiform seizures.
Developmental patterns of the C. elegans neural circuits using community detection.
Wang X, Qin R, Shi G … +2 more , Zheng L, Liu H
Neuroscience · 2026 Jun · PMID 42320724 · Publisher ↗
C. elegans serves as a prime model for dissecting the developmental trajectories of nervous systems, yet, few studies have probed the functional development of its neural connectome. In this work, we utilized an enhanced...
C. elegans serves as a prime model for dissecting the developmental trajectories of nervous systems, yet, few studies have probed the functional development of its neural connectome. In this work, we utilized an enhanced version of BIGCLAM, a community detection algorithm tailored for weighted and directed networks that explicitly captures overlapping modules, to delineate neural circuits across C. elegans' developmental stages (from L1 larvae to adults) based on developmental neural connectome datasets. Our findings reveal that neural circuits are initially small and simple during early development, whereas they undergo marked expansion, increased structural complexity and functional diversification in later phases. Notably, neural circuits emerge progressively: neurons integrate sequentially into functional assemblies, enabling a transition from basic survival-centric behaviors to complex behavioral repertoires. In contrast to conventional experiment-based approaches, this topological analysis framework facilitates quasi-precise detection of neural circuits with minimal resource consumption.
Age-related susceptibility to paraquat-induced neurotoxicity in male wistar rats: effects on neurobehaviour, substantia nigra cytoarchitecture, and alpha-synuclein levels.
Ichie K, Asomugha A, Okafor I
BMC Neurosci · 2026 Jun · PMID 42316013 · Full text
BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder strongly associated with dopaminergic neuronal degeneration and alpha-synuclein pathology. Paraquat (PQ) has been implicated in Parkinsonia...
BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder strongly associated with dopaminergic neuronal degeneration and alpha-synuclein pathology. Paraquat (PQ) has been implicated in Parkinsonian neurodegeneration; however, the influence of age on susceptibility to PQ-induced neuropathology remains insufficiently characterized. AIM: This study investigated age-dependent effects of paraquat exposure on neurobehaviour, substantia nigra histomorphology, and serum alpha-synuclein levels in male Wistar rats. METHODS: Sixty-three male Wistar rats were assigned into juvenile, young adult, and adult age categories, each further subdivided into control, PQ-treated, and PQ+recovery groups. Paraquat (10 mg/kg, intraperitoneally) was administered twice weekly for three weeks. Recovery groups were maintained for a two-month post-exposure period. Neurobehavioral assessments were conducted to evaluate locomotor and anxiety-related functions. Serum and nigral alpha-synuclein concentrations were quantified using enzyme-linked immunosorbent assay (ELISA), while histological examination of the substantia nigra was performed to assess neuronal integrity. RESULTS: Adult rats exhibited a significant reduction in locomotor activity following PQ exposure (p = 0.020) and showed more prominent histopathological alterations within the substantia nigra compared with juvenile and young-adult animals. Although improvement in tissue architecture was observed following paraquat withdrawal, residual alterations persisted, particularly in adults. Nigral alpha-synuclein concentrations did not differ significantly among treatment groups in any age cohort. Serum alpha-synuclein levels were similarly unchanged in most groups, except for a reduction observed in recovering young-adult animals (p = 0.039). CONCLUSION: Age influences vulnerability to PQ-induced neurotoxicity, with adult animals showing greater susceptibility to behavioral and histological damage. However, serum total alpha-synuclein levels did not consistently parallel central neuropathology, suggesting limited reliability as a standalone peripheral biomarker of PQ-induced Parkinsonism.
Unilateral striatal deep brain stimulation improves cognitive control.
Sachse EM, Dastin-van Rijn EM, Bennek JP … +5 more , Buccini MC, Mensinger ME, Iacobucci FA, Reimer AE, Widge AS
J Neurosci · 2026 Jun · PMID 42315348 · Publisher ↗
Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VCVS) can treat obsessive-compulsive disorder (OCD) and other psychiatric conditions. Yet, optimizing its clinical efficacy is a major challenge, ofte...
Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VCVS) can treat obsessive-compulsive disorder (OCD) and other psychiatric conditions. Yet, optimizing its clinical efficacy is a major challenge, often hindered by incomplete knowledge of how stimulation parameters and targets affect neural activity and behavior. VCVS DBS is thought to work in part by improving cognitive control, an important decision-making component that is impaired in OCD and other illnesses. The magnitude of this cognitive control enhancement was shown to be lateralized, with right-unilateral stimulation being the most effective. Prior work developed a preclinical model of VCVS DBS by leveraging the cognitive control construct, which can be measured in humans and rodents and is modulated by analogous brain circuits. However, this work did not address laterality effects observed in humans or examine left/right stimulation differences. These effects may be critical for maximizing therapeutic benefit while avoiding aversive outcomes. This study aimed to investigate lateralization in the rodent model, where bilateral stimulation of the mid-striatum was previously shown to improve cognitive control. Right and left-unilateral stimulation reduced response times without changing accuracy, replicating the cognitive control improvement from bilateral stimulation. With computational modeling, we show that bilateral and unilateral stimulation modifies the same decision-making variables to drive this behavior change. We also establish that females have the same cognitive control improvement from stimulation as males. These findings increase our understanding of cognitive control circuits and strengthen the validity of the rodent model as a translational platform to study VCVS DBS's therapeutic mechanisms. Here, we demonstrate that stimulating just one side of the brain (e.g. unilaterally) can be as effective as bilateral stimulation for improving cognitive control, the ability to adjust thoughts and decisions in response to environmental changes. These findings in rodents match results from prior human deep brain stimulation (DBS) studies, highlighting the validity of this preclinical model to study DBS's therapeutic mechanisms. We hypothesize that unilateral stimulation may be preferable to maximize cognitive benefits without causing off-target effects, while also reducing surgical invasiveness. Further, we demonstrate that females have the same cognitive control improvement from stimulation as males. Overall, this work answers important outstanding clinical questions regarding laterality and sex in DBS therapies for psychiatric illnesses.
Investigation of the task- or muscle-specific organisation of motor cortex representations of shoulder muscles in pain-free adults.
Ma Y, Nardese G, Kerr G … +2 more , van den Hoorn W, Hodges PW
Neuroscience · 2026 Jun · PMID 42314795 · Publisher ↗
Coordination between the deltoid and rotator cuff (including subscapularis) muscles is critical to maintain dynamic stability of the glenohumeral joint. Organisation of the primary motor cortex (M1) might provide insight...
Coordination between the deltoid and rotator cuff (including subscapularis) muscles is critical to maintain dynamic stability of the glenohumeral joint. Organisation of the primary motor cortex (M1) might provide insight into how this coordination is controlled. Task specific organisation of the motor cortex would imply that individual muscles are controlled by multiple cortical regions subserving different functions, and that multiple muscles involved in a task are controlled by a common region. Alternatively, the cortex might be organised in a muscle-specific manner. This study compared these alternatives. Transcranial Magnetic Stimulation (TMS) was used to investigate the motor cortex representations of the middle deltoid and subscapularis muscles during two tasks (isometric abduction and internal rotation) in nineteen pain-free adults. Muscle-specific hotspots and active motor thresholds were identified. TMS maps were generated for each muscle during the tasks. Novel measures were used to quantify the extent of overlap between TMS map pairs. Overlap was observed between deltoid and subscapularis maps during the same task - consistent with TASK-specific organization. Overlap was also evident within the same muscle between tasks - aligning with a MUSCLE-specific organization. Subscapularis had a greater bias to MUSCLE-specific organisation. Results suggest coexisting principles of MUSCLE- and TASK-specific representations in M1 for the control of shoulder muscles. Differences between organisation of the rotator cuff and deltoid muscles might have functional relevance. This study provides insight into the M1 cortical organization principles underlying shoulder motor control.
Auditory evoked potentials in suspected idiopathic normal pressure hydrocephalus: longitudinal associations with tap test and clinical outcomes.
Silva LAF, Mielle LP, Santos NP … +2 more , Matas SLA, Matas CG
Neuroscience · 2026 Jun · PMID 42314794 · Publisher ↗
New biomarkers are needed to improve the clinical profile of idiopathic normal pressure hydrocephalus (iNPH), a potentially reversible cause of cognitive and functional decline in older adults. The Tap Test (TT) is commo...
New biomarkers are needed to improve the clinical profile of idiopathic normal pressure hydrocephalus (iNPH), a potentially reversible cause of cognitive and functional decline in older adults. The Tap Test (TT) is commonly used to support clinical decision-making regarding ventriculoperitoneal shunt (VPS) surgery; however, objective markers of treatment response remain limited. This study aimed to investigate whether auditory brainstem response (ABR) and cortical auditory evoked potentials (CAEP) measures are associated with clinical response to the TT and with longitudinal clinical outcomes in older adults with suspected iNPH. Fifty-five older adults (mean age: 75 ± 7.04 years) were evaluated before and after lumbar puncture and during follow-up (3-12 months). Participants were categorized into three clinical outcome groups: TT-negative without VPS, TT-positive without VPS, and those who underwent VPS. Clinical assessment included gait and neuropsychological testing, while neurophysiological evaluation comprised ABR and CAEP. A high prevalence of previously undiagnosed hearing loss highlighted the importance of systematic audiological assessment in this population, given its potential impact on cognition and functional outcomes. ABR abnormalities were frequent but not associated with clinical changes. CAEP did not reflect response to lumbar puncture during the TT. However, shorter P1 latencies were associated with better gait performance, and reduced P2 latency after VPS may reflect improved cortical processing. CAEP measures, particularly P1 and P2 latencies, represent a potential candidate marker for monitoring postoperative improvement in older adults with iNPH; however, this requires further validation in future studies.
Astaxanthin alleviates ischemia-reperfusion injury by regulating the JAK2/STAT3 signaling pathway.
Zhang Y, Jiang J, Ma Z … +1 more , Gong H
Int J Neurosci · 2026 Jun · PMID 42310989 · Publisher ↗
BACKGROUND: Cerebral ischemia-reperfusion injury (CIRI) lacks effective treatments. Astaxanthin (AST) ameliorates CIRI, but the underlying mechanisms remain unclear. METHODS: An oxygen-glucose deprivation/reoxygenation (...
BACKGROUND: Cerebral ischemia-reperfusion injury (CIRI) lacks effective treatments. Astaxanthin (AST) ameliorates CIRI, but the underlying mechanisms remain unclear. METHODS: An oxygen-glucose deprivation/reoxygenation (OGD/R) model in PC12 cells and a middle cerebral artery occlusion/reperfusion (MCAO/R) rat model were used. Cell viability (MTT), apoptosis (flow cytometry), oxidative damage (8-OHdG, 4-HNE, MDA, ROS), inflammatory factors (TNF-α, IL-1β, IL-6, MCP-1), and JAK2/STAT3 pathway proteins (p-JAK2, p-STAT3) were assessed, with or without AST treatment and JAK2 agonist intervention. RESULTS: OGD/R significantly reduced PC12 cell viability, increased apoptosis, and elevated oxidative and inflammatory markers, while activating JAK2/STAT3. AST treatment reversed these effects-promoting proliferation, inhibiting apoptosis, and reducing damage markers. AST also suppressed p-JAK2 and p-STAT3 expression. Activation of the JAK2/STAT3 pathway abolished AST's protective effects against OGD/R-induced damage. In vivo, AST effectively alleviated ischemia-reperfusion injury in rats.
Non-invasive deep-brain neuromodulation by transcranial radio frequency stimulation.
Yaghmazadeh O
Nat Rev Neurosci · 2026 Jun · PMID 42310407 · Publisher ↗
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Heading into the wild: setting the course to natural neuroscience.
Beetz MJ
Nat Rev Neurosci · 2026 Jun · PMID 42310406 · Publisher ↗
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Stage- and Region-Dependent Proteomic Alterations in a Mouse Model of Creatine Transporter Deficiency.
Ito S, Iwata Y, Uemura T … +14 more , Sugimoto M, Kumabe H, Miyano A, Nakamura T, Tashiro N, Ieiri M, Umezaki M, Chikamatsu S, Masuda T, Nakao S, Nakagata N, Takeo T, Araki K, Ohtsuki S
J Neurosci · 2026 Jun · PMID 42309815 · Publisher ↗
SLC6A8 encodes the creatine transporter (CRT), which mediates creatine transport across the plasma membrane in the brain, including the blood-brain barrier and neurons. Creatine transporter deficiency (CTD), caused by pa...
SLC6A8 encodes the creatine transporter (CRT), which mediates creatine transport across the plasma membrane in the brain, including the blood-brain barrier and neurons. Creatine transporter deficiency (CTD), caused by pathogenic variants in , leads to cerebral creatine depletion and cognitive impairment. Here, we investigated the developmental molecular mechanisms underlying CTD using the pathogenic c.1681G>C (G561R) variant of , which corresponds to a variant identified in in a patient with CTD. analyses using HEK293 cells expressing mutant mouse CRT carrying the G561R variant demonstrated impaired N-glycan maturation and plasma membrane localization of the transporter, resulting in markedly reduced creatine uptake, consistent with previous reports on the corresponding human CRT variant. To investigate the in vivo effects of this pathogenic variant, we generated CRT-G561R knock-in mice by introducing the c.1681G>C point mutation into the mouse gene using the CRISPR/Cas9 system. These male mice exhibited severe reductions in brain creatine levels, postnatal growth retardation, and impaired spatial memory, despite preserved gross brain morphology. Quantitative proteomic analyses of the hippocampus and cerebral cortex during postnatal development revealed region-dependent protein alterations in CTD. The hippocampus showed pronounced early postnatal remodeling involving proteins related to actin cytoskeleton organization and vesicle-mediated membrane trafficking, whereas the cerebral cortex exhibited a more gradual response involving creatine biosynthesis-related enzymes and later-emerging mitochondrial pathways, including the mitochondrial translation machinery. These findings demonstrate stage- and region-dependent proteomic remodeling during postnatal brain development in CTD. Creatine transporter deficiency (CTD) causes cerebral creatine depletion and intellectual disability; however, the developmental mechanisms linking creatine loss to brain dysfunction remain unclear. We performed developmental proteomic profiling of the hippocampus and cerebral cortex using a mouse model carrying a pathogenic variant identified in patients with CTD. Creatine transporter dysfunction induces distinct region- and stage-dependent molecular responses during postnatal brain maturation. The hippocampus shows early alterations in cytoskeleton-dependent membrane trafficking pathways, consistent with impaired synaptic and circuit maturation, whereas the cerebral cortex exhibits progressive metabolic and mitochondrial adaptations. These findings suggest that impaired creatine-dependent energy buffering disrupts distinct developmental programs across brain regions, potentially contributing to cognitive dysfunction by hindering early hippocampal circuit maturation.
Astrocytic FTO-dependent m6A demethylation drives sevoflurane-induced perioperative neurocognitive disorders in mice.
Li J, Liao Z, Zhang K … +9 more , Liu Y, Xu H, Cao D, Yang J, Han J, Zeng L, Shen Z, Wu Y, Li J
J Neurosci · 2026 Jun · PMID 42309814 · Publisher ↗
The pathogenesis of perioperative neurocognitive disorders (PND) involves a complex interplay of genetic vulnerability and environmental insults, with epigenetic regulation acting as a dynamic mediator. However, the cell...
The pathogenesis of perioperative neurocognitive disorders (PND) involves a complex interplay of genetic vulnerability and environmental insults, with epigenetic regulation acting as a dynamic mediator. However, the cell-specific epitranscriptomic responses to perioperative stressors like sevoflurane anesthesia, and their functional consequences for cognitive decline, are not well defined. Here, we report that the m6A demethylase FTO is significantly upregulated in the medial prefrontal cortex (mPFC) of male mice exposed to sevoflurane anesthesia. Astrocytic FTO, but not neuronal or endothelial FTO, is highly sensitive to sevoflurane exposure. Conditional knockout of FTO in astrocytes attenuated sevoflurane-induced cognitive deficits, while astrocyte-specific FTO overexpression exacerbated sevoflurane-induced cognitive deficits. Mechanistically, astrocytic FTO mediated m6A demethylation of glutamate transporter-1 (GLT-1) mRNA, leading to enhanced GLT-1 protein expression and aberrant glutamatergic transmission. Sevoflurane exposure disrupted synaptic transmission, neuronal morphology, and calcium activity in the mPFC, which were rescued by astrocytic FTO deletion. Supplementation with the methyl donor S-adenosylmethionine (SAMe) normalized m6A levels and improved cognitive performance. This study demonstrates that astrocytic FTO is a critical epitranscriptomic modulator of sevoflurane-induced PND and a potential therapeutic target for PND. PND are a major clinical concern for which effective mechanism-based interventions are lacking. This study identifies astrocytic FTO as a cell-type-selective epitranscriptomic driver of sevoflurane-induced PND and establishes that its m6A-demethylase activity disrupts glutamate homeostasis by post-transcriptionally regulating the astrocytic glutamate transporter GLT-1. Astrocyte-restricted deletion of FTO preserves synaptic transmission, neuronal structure, and calcium dynamics, thereby preventing cognitive decline, while astrocytic FTO overexpression exacerbates deficits. Therapeutic restoration of m6A methylation with the methyl donor SAMe normalizes the epitranscriptomic landscape and rescues cognitive function. These findings reveal astrocytic m6A regulation as a previously unrecognized pathogenic mechanism and a druggable target for PND.
Multidimensional feature tuning in category-selective areas of human visual cortex.
van Dyck LE, Hebart MN, Dobs K
J Neurosci · 2026 Jun · PMID 42309813 · Publisher ↗
Two prominent accounts describe the functional organization of human high-level visual cortex. A categorical view emphasizes category-selective areas, while a dimensional view highlights continuous feature maps spanning...
Two prominent accounts describe the functional organization of human high-level visual cortex. A categorical view emphasizes category-selective areas, while a dimensional view highlights continuous feature maps spanning these areas. Here, we asked whether these two views reflect complementary expressions of the same underlying organization. Using a data-driven decomposition of fMRI responses from human participants (female and male) in face-, body-, and scene-selective areas, we identified spatially overlapping activity patterns that were shared across individuals. Each area encoded multiple interpretable dimensions capturing both finer within-category and coarser between-category distinctions, even in the most category-selective voxels. These dimensions formed distinct clusters within category-selective areas but extended as distributed maps across visual cortex. Together, these findings reveal an underlying organization that links category-selective areas to continuous feature maps, thereby reconciling categorical and dimensional accounts of high-level visual cortex. What functional organization in human visual cortex could give rise to both category-selective areas and continuous feature maps? Using a data-driven decomposition of fMRI responses to natural images, we identified interpretable dimensions that explain activity in face-, body-, and scene-selective areas. These dimensions captured both within-category and between-category distinctions, formed distinct clusters within category-selective areas, and extended as distributed maps across visual cortex. This underlying functional organization reconciles categorical and dimensional accounts and helps explain how visual cortex balances specificity and flexibility to support diverse perceptual and cognitive demands.
Targeting Circadian Rhythm to Treat Cancer Pain.
Sankar N
J Neurosci · 2026 Jun · PMID 42309811 · Full text
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Plant-based neuroprotection against memory impairment: Insights from Drosophila melanogaster models of neurodegenerative diseases.
Cynthia Irene Kasi, Azhagu Saravana Babu Packirisamy, Meivelu Moovendhan
Neuroscience · 2026 Jun · PMID 42309440 · Publisher ↗
Neurodegenerative diseases are characterised by the progressive dysfunction of neurons, and memory impairment is one of their most debilitating clinical manifestations. The etiopathogenic mechanisms are multifactorial, s...
Neurodegenerative diseases are characterised by the progressive dysfunction of neurons, and memory impairment is one of their most debilitating clinical manifestations. The etiopathogenic mechanisms are multifactorial, such as protein misfolding, oxidative stress, and mitochondrial malfunction and synaptic degeneration along with neuroinflammation. As yet, therapists still focus mainly on symptomatic treatment and no agents are found to halt or reverse the decline of cognitive, indicating what is more needed is other kinds of neuroprotective strategy. In this context, the plant-derived phytochemicals stand out as promising candidates owing to their multi-targeted mode of action, favourable safety profile and long-standing use in traditional medicine systems. These bioactive compounds modulate oxidative stress, inflammatory signalling, neurotransmitter balance, apoptotic pathways and protein aggregation to elicit neuroprotection. The attention of the research community has also turned towards using Drosophila melanogaster as a model system for neurodegenerative-related studies due to its genetic tractability, accessible behavioural learning and memory tests, and the evolutionary conservation of potentially important biological pathways. This review consolidates recent evidence regarding plant-based neuroprotective strategies against memory impairment, with a specific focus on mechanistic mechanisms elucidated from Drosophila models of neurodegenerative diseases. Integrating findings across molecular, cellular and behavioural levels, the review illustrates the therapeutic promise of phytochemicals and reaffirms Drosophila as a valuable preclinical tool. It also addresses practical translational considerations, such as bioavailability, standardisation, and clinical validation, and sets forth future directions for effectiveness of plant-based interventions to facilitate improvements out in the real world.
Red-shifted GRAB acetylcholine sensors for multiplex imaging in vivo.
Xie S, Miao X, Li G … +10 more , Zheng Y, Li M, Ji E, Wang J, Li S, Cai R, Geng L, Feng J, Wei C, Li Y
Nat Neurosci · 2026 Jun · PMID 42303796 · Publisher ↗
The neurotransmitter acetylcholine (ACh) is essential in both the central and peripheral nervous systems. Recent studies highlight the significance of interactions between ACh and various neuromodulators in regulating co...
The neurotransmitter acetylcholine (ACh) is essential in both the central and peripheral nervous systems. Recent studies highlight the significance of interactions between ACh and various neuromodulators in regulating complex behaviors. The ability to simultaneously image ACh and other neuromodulators can provide valuable information regarding the mechanisms underlying these behaviors. Here we developed a series of red fluorescent G-protein-coupled receptor activation-based ACh sensors, with a wide detection range and expanded spectral profile. The high-affinity sensor rACh1h reliably detects ACh release in various brain regions, including the nucleus accumbens, amygdala, hippocampus and cortex. Moreover, rACh1h can be coexpressed with green fluorescent sensors to record ACh release together with other neurochemicals in various behavioral contexts using fiber photometry, mesoscopic imaging and two-photon imaging with high spatiotemporal resolution.
Different brain regions support deliberation during food choice in disordered and healthy eating.
Muratore AF, Hartnett EA, Foerde K … +5 more , Uniacke BW, Walsh BT, Steinglass JE, Shohamy D, Bakkour A
J Neurosci · 2026 Jun · PMID 42303575 · Publisher ↗
The brain is wired to drive behavior towards foods that are high in sugar and fat. Yet, individuals with anorexia nervosa (AN) prefer low-sugar and low-fat foods to the point of starvation and even death. Here, we aimed...
The brain is wired to drive behavior towards foods that are high in sugar and fat. Yet, individuals with anorexia nervosa (AN) prefer low-sugar and low-fat foods to the point of starvation and even death. Here, we aimed to understand how alterations in decision-making processes and associated neural activity contribute to the pattern of maladaptive food-related decisions observed in AN. We combined decision-making tasks with computational modeling of behavior and fMRI to examine food-specific and general (nonfood)-related decisions in female individuals with AN and healthy controls (HC). Results from this pre-registered study suggest that patients with AN, like HC, employ a decision-making process that relies on sampling and evaluating evidence, regardless of the type of decision. However, neural activity patterns differed between groups when deliberating about what to eat: food choice-related activation among HC was localized to the hippocampus, whereas individuals with AN engaged both the hippocampus and the striatum, regions apparently serving as sources of evidence in the decision process. These findings suggest that the maladaptive reversal of food preferences in AN may be attributable to reliance on different inputs to the process that leads to restrictive food choice, rather than a maladaptive decision process Disordered eating often involves maladaptive choices about what to eat. The present research shows that the decision-making unfolds similarly in healthy individuals and patients with anorexia nervosa but the brain regions that support deliberation about what to eat differ. Together, the findings suggest that the inputs to the decision process, rather than the decision process should be a point of focus in the search for novel treatments of eating disorders.
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