Neuroscience最新文献

{"title":"Reliable and dynamic monitoring changes in cortical excitation and inhibition balance using aperiodic 1/f slope: functions, diseases and drug effects","authors":"Zeyi Wang ,&nbsp;Sungchil Yang ,&nbsp;Jianping Lu ,&nbsp;Qiang Zhou","doi":"10.1016/j.neuroscience.2025.12.050","DOIUrl":"10.1016/j.neuroscience.2025.12.050","url":null,"abstract":"<div><div>Understanding the excitation/inhibition (E/I) balance is fundamental to deciphering cortical circuit dynamics, supporting cognition, and elucidating the pathophysiology of brain disorders, yet methods for assessing E/I balance <em>in vivo</em> remain limited. While recent studies have proposed the aperiodic component (1/f slope) of the local field potentials (LFPs) power spectrum as a potential indicator of E/I balance, this hypothesis has lacked systematic, multi-level <em>in vivo</em> validation. Here, we systematically tested the hypothesis that the aperiodic 1/f slope can serve as a reliable proxy for dynamically monitoring change in E/I balance. In freely moving male mice, we first optimized the analytical parameters for the 1/f slope. We then demonstrated that the slope quantitatively tracks shifts in inhibition induced by pharmacological manipulations in a dose-dependent manner, captures the rapid dynamic shift to inhibition induced by cell-type-specific optogenetic manipulation, and shows generality across drugs altering E/I with diverse mechanisms. On an applied level, we show that the 1/f slope tracks performance-related neural dynamics during a working memory task and indicates the direction of E/I balance in mouse models of epilepsy and depression. Collectively, our findings establish the 1/f slope as a reliable, rapid and sensitive proxy for monitoring E/I balance shift, offering a potential, practical tool for monitoring brain dynamics and as a biomarker for translational research.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"595 ","pages":"Pages 9-19"},"PeriodicalIF":2.8,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145810705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of cofilin 1 phosphorylation induces juvenile-like plasticity in the adult mouse visual cortex","authors":"Agustina Dapueto ,&nbsp;Emilia Hayek ,&nbsp;Alejo Acuña ,&nbsp;Bruno Pannunzio ,&nbsp;Leonel Gomez ,&nbsp;Francesco M. Rossi","doi":"10.1016/j.neuroscience.2026.01.003","DOIUrl":"10.1016/j.neuroscience.2026.01.003","url":null,"abstract":"<div><div>Cofilin 1 is an actin-depolymerizing protein that plays a fundamental role in actin dynamics, particularly within dendritic spines, where it has been implicated in both structural and functional plasticity. We recently demonstrated, using a combination of differential proteomics, western blot and immunohistochemistry, that the expression of cofilin 1 and its inactive phosphorylated form is dynamically regulated in the mouse visual cortex. Expression levels change across critical periods of postnatal development and are modulated by visual experience, suggesting that cofilin 1 plays a dynamic role in synaptic remodeling during windows of heightened cortical plasticity.</div><div>In this study, we sought to determine whether cofilin 1 influences experience-dependent plasticity in the adult visual cortex, a stage where plasticity is more restricted but still inducible under specific conditions. Specifically, we administered a synthetic peptide inhibitor of cofilin 1 activity <em>in vivo</em> (PCOF). Following monocular deprivation, adult mice received either the PCOF peptide or a control peptide. Structural plasticity was assessed by quantifying dendritic spine density using Golgi-like staining, while visual plasticity was evaluated by measuring visual acuity through the optomotor response test.</div><div>Our results show that, in adult mice treated with the PCOF peptide − but not in controls − monocular deprivation led to a significant reduction in dendritic spine density in the contralateral visual cortex, as well as a decrease in visual acuity of the previously deprived eye. These findings indicate that cofilin 1 activity is crucial for the regulation of experience-dependent plasticity in the adult mouse visual cortex.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"595 ","pages":"Pages 262-269"},"PeriodicalIF":2.8,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145934167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations of functional connectivity between hyperdirect pathway regions and outside regions in Parkinson’s disease patients with freezing of gait","authors":"Yuting Li ,&nbsp;Shuwen Bo ,&nbsp;Jian-Feng Qu ,&nbsp;Xiuhang Ruan ,&nbsp;Bin Chen ,&nbsp;Mengyan Li ,&nbsp;Yujian Zou ,&nbsp;Changzheng Shi ,&nbsp;Xinhua Wei","doi":"10.1016/j.neuroscience.2025.12.058","DOIUrl":"10.1016/j.neuroscience.2025.12.058","url":null,"abstract":"<div><div>Emerging neuroimaging evidence has propelled the formulation of the hypothesis that freezing of gait (FOG) in Parkinson’s disease (PD) arises from dysfunction within the locomotor network. However, to date, there has been a lack of functional connectivity analyses targeting the hyperdirect pathway (HDP) to explore this hypothesis. In this study, we investigate impaired communication within the HDP neural circuitry in FOG patients. Fifty-nine PD patients (33 PD-nFOG and 26 PD-FOG) and thirty matched healthy controls underwent resting-state functional magnetic resonance imaging. Both ROI-wise and voxel-wise based resting-state functional connectivity were calculated in this study. No group differences were observed in the ROI-wise functional connectivity among the regions within the HDP. However, significant reduced functional connectivity based on voxel-wise analysis were observed between the HDP and several brain regions, including the default mode network (DMN), sensorimotor cortex, limbic system and cerebellum in PD, which were associated with psychiatric symptoms, emotional decline, and motor dysfunction. Of note, compared to PD-nFOG, PD-FOG showed increased functional connectivity between the HDP and the cerebellum and the middle occipital gyrus, which was associated with motor impairment in the contralateral limbs. These data extend neuroimaging evidence on that compensatory increased functional connectivity in HDP in FOG patients may indicate a failure compensate for clinical manifestations of limb akinesia, and may represent a loss of low-level automatic control of gait regulation by the basal ganglia.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"595 ","pages":"Pages 220-228"},"PeriodicalIF":2.8,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EEG theta dynamics for error processing during online movement control","authors":"Sarah Kessouri ,&nbsp;Frederic R Danion ,&nbsp;Jean-François Lepage ,&nbsp;Pierre-Michel Bernier","doi":"10.1016/j.neuroscience.2025.12.065","DOIUrl":"10.1016/j.neuroscience.2025.12.065","url":null,"abstract":"<div><div>To ensure optimal visuomotor feedback control during manual tracking, the brain must continuously monitor the error between the hand and the target. Modulations in the theta band (3–8 Hz) are related to error processing, but this has been mainly shown in cognitive control contexts. Hence, their relationship with hand-target errors during online control remains unclear. Here we assessed the impact of motor error processing on EEG theta-band activity in 29 healthy participants while they performed continuous tracking of a moving target with their dominant (right) hand. Two conditions were used to manipulate error processing demands: 1) in the Repeated condition, the same target trajectory was presented 80 times, allowing participants to implicitly learn the pattern and reduce tracking errors; 2) in the Random condition, 80 different trajectories were used, inducing persistent high tracking errors. Behavioral analyses confirmed that tracking errors were significantly higher in the Random than in the Repeated condition. Importantly, EEG theta power was also significantly higher in the Random condition, with a peak difference occurring at electrodes overlaying the left sensorimotor regions. This effect was selective to theta activity, as there was no modulation in alpha- (8–12 Hz) and beta-band (15–30 Hz) activity. Overall, this study extends the role of theta oscillations to online error processing in the context of motor control. It is possible that theta modulations reflected cortical activity mediating the communication and integration of information within sensorimotor circuits including the motor, premotor and parietal cortex, which are known to mediate online movement control.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"595 ","pages":"Pages 280-289"},"PeriodicalIF":2.8,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145864274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered cerebral thyroid hormone, WNT and NOTCH signalling and impaired myelination following intrauterine growth restriction in rats","authors":"Aminath Azhan ,&nbsp;Angela L. Cumberland ,&nbsp;Ginevra Chincarini ,&nbsp;Mikaela Barresi ,&nbsp;Nadia Hale ,&nbsp;David H. Rowitch ,&nbsp;Flora Wong ,&nbsp;David W. Walker ,&nbsp;Mary Tolcos","doi":"10.1016/j.neuroscience.2025.12.068","DOIUrl":"10.1016/j.neuroscience.2025.12.068","url":null,"abstract":"<div><div>Intrauterine growth restriction (IUGR) is associated with impaired brain development, including hypomyelination. Preclinical studies suggest that reduced myelination in IUGR may result from delayed oligodendrocyte maturation, but the mechanisms remain unclear. We examined whether altered expression of positive (thyroid hormone, TH) and negative (WNT and NOTCH signalling) regulators of oligodendrocyte maturation and myelination contribute to this delay. We induced IUGR in pregnant rats via bilateral uterine vessel ligation at embryonic day 18; sham surgeries generated controls. At postnatal day (P) 7, P14, and P35, we assessed oligodendrocytes (Olig2, APC) and myelinated fibres (MBP) by immunostaining, and measured expression of TH-related and WNT/NOTCH pathway genes using RT-qPCR in the cerebral white matter (P7 and P14 only). We found that IUGR offspring exhibited reduced MBP-immunoreactivity in the corpus callosum (P7) and external capsule (P7 and P14), and decreased density of APC-positive oligodendrocytes at P14. No difference in these measures were observed at P35, nor in the density of Olig2-positive cells at any age. At P7, IUGR brains showed increased <em>Tcf4</em>, <em>Delta1</em> and <em>Hes5</em> expression (WNT/NOTCH), and reduced <em>Mct8</em>, <em>Oatp1c1, Dio1</em>, and <em>Dio3</em> mRNA expression (TH signalling), which were not different between groups by P14. Reductions in <em>Mct8</em> mRNA expression were confirmed by immunohistochemical analysis. Our findings suggest that alteration of TH, WNT, and NOTCH signalling may be associated with impaired oligodendrocyte maturation and myelination in IUGR, providing insight into the mechanisms underlying white matter injury in IUGR infants.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"595 ","pages":"Pages 138-153"},"PeriodicalIF":2.8,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tk2 deficiency–mediated mitochondrial dysfunction drives neuroinflammation and seizure frequency in epilepsy","authors":"Xi Zhang ,&nbsp;Jiahao Lian ,&nbsp;Yongbin Pang ,&nbsp;Haohao Cui ,&nbsp;Xiaobo Ye ,&nbsp;Qiang Meng ,&nbsp;Yong Liu ,&nbsp;Huanfa Li ,&nbsp;Yutao Ren ,&nbsp;Ying Zhang ,&nbsp;Hua Zhang ,&nbsp;Hao Wu","doi":"10.1016/j.neuroscience.2026.01.001","DOIUrl":"10.1016/j.neuroscience.2026.01.001","url":null,"abstract":"<div><div>Seizure frequency is a key indicator of disease severity and treatment response in epilepsy, yet its molecular determinants remain unclear. We performed proteomic profiling of resected epileptogenic brain tissue from patients, stratified by seizure frequency and by temporal versus extratemporal origin, and functionally validated candidate differentially expressed proteins (DEPs). Seizure foci of high and low frequencies in distinct brain regions displayed region-specific proteomic profiles. However, bioinformatic analyses of both temporal and extratemporal cohorts consistently showed that the down-regulated proteins converge on mitochondrial localization and function. Among these, mitochondrial thymidine kinase 2 (Tk2) exhibited a robust inverse correlation with seizure frequency, a finding confirmed in patient tissues across different frequency groups. Consistently, Tk2 expression was reduced across multiple brain regions in two seizure models induced by pilocarpine or ferric chloride. Mechanistically, loss of Tk2 activated the cGAS-STING pathway, upregulated inflammatory genes, and then increased seizure susceptibility. These findings identify Tk2 as a mitochondrial kinase that couples energetic failure to neuroinflammation, and provide a mechanistic basis for targeting the Tk2-mitochondria-inflammation axis in epilepsy.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"595 ","pages":"Pages 171-186"},"PeriodicalIF":2.8,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective effects of aegeline against LPS-induced memory dysfunction: involvement of hippocampal cholinergic/proinflammatory cytokines receptor modulation and insilico insight","authors":"Khalid Saad Alharbi ,&nbsp;Sattam Khulaif Alenezi ,&nbsp;Tariq G Alsahli ,&nbsp;Reem ALQahtani ,&nbsp;Muhammad Afzal ,&nbsp;Imran Kazmi ,&nbsp;Nadeem Sayyed","doi":"10.1016/j.neuroscience.2025.12.048","DOIUrl":"10.1016/j.neuroscience.2025.12.048","url":null,"abstract":"<div><h3>Aims</h3><div>This study aimed to evaluate the neuroprotective effects of aegeline on lipopolysaccharide (LPS) −induced cognitive dysfunction in rats.</div></div><div><h3>Background</h3><div>The global rise in neuroinflammatory and cognitive disorders demands safe and effective plant-based neuroprotective agents. LPS is a potent endotoxin that triggers inflammation and tissue damage. Aegeline, a hydroxyamide derived from <em>Aegle marmelos</em>, exhibits anti-inflammatory and antioxidant properties. However, its ability to modulate hippocampal cholinergic and proinflammatory cytokine receptors, as well as to protect against LPS-induced memory impairment, remains unexplored.</div></div><div><h3>Methods</h3><div>Aegeline was administered at doses of 5 and 10 mg/kg for seven days to Wistar rats. Behavioral tests included the Y-maze and the Morris water maze (MWM). Biochemical analyses measured acetylcholinesterase (AChE), choline acetyltransferase (ChAT), malondialdehyde (MDA), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), nitric oxide (NO), and inflammatory cytokines: tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6. Furthermore, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and caspase-3 markers were evaluated. Additionally, in silico molecular docking and molecular dynamics simulations (MDS) were conducted.</div></div><div><h3>Results</h3><div>Aegeline treatment improved performance in the Y-maze and MWM tests. It reduced AChE, proinflammatory cytokine, NF-κB, oxidative stress marker, and caspase-3 levels. Antioxidant enzymes and ChAT levels were increased. In silico, aegeline showed strong binding to protein 7JRA with a binding energy of −9.289 kcal/mol, respectively. MDS confirmed the stable interactions with key therapeutic targets.</div></div><div><h3>Conclusion</h3><div>Aegeline improved cognition, reduced inflammation and oxidative stress, and enhanced antioxidant and cholinergic activity. Its strong molecular binding supports its potential as a neuroprotective agent against memory impairment.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"595 ","pages":"Pages 112-129"},"PeriodicalIF":2.8,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antidepressants as modulators of P2X7 receptor activity","authors":"Vitor Nascimento Vidal ,&nbsp;Guilherme Pegas Teixeira ,&nbsp;Juliana Vieira Faria ,&nbsp;Jonathas Albertino de Souza Oliveira ,&nbsp;Murilo Lamim Bello ,&nbsp;Leandro Rocha ,&nbsp;Robson Xavier Faria","doi":"10.1016/j.neuroscience.2025.12.042","DOIUrl":"10.1016/j.neuroscience.2025.12.042","url":null,"abstract":"<div><div>According to the Pan American Health Organization, more than 300 million people suffer from depression worldwide. Despite the alarming numbers, current drug treatments produce partial results, as they focus on only one pillar of depression: neurotransmitters. Most current medications for depression focus only on stimulating increased levels of neurotransmitters related to feelings of well-being and happiness, such as serotonin and norepinephrine, which, despite providing relief, do not produce such impressive results for patients. A significant and scientifically endorsed point regarding depression is neuroinflammation. The relationship between inflammation in the body and the development or worsening of depression has been strongly reinforced by neuroscientific studies. Studies have also shown that depressed patients have increased levels of inflammatory cytokines. Antidepressants have already demonstrated anti-inflammatory activity, stimulating the production of anti-inflammatory cytokines and reducing the production of oxidative radicals, as in the case of fluoxetine and paroxetine. In depression, P2X7 receptor expression is increased. This receptor is activated, and greater expression produces a depressive phenotype, while its blockade has antidepressant effects. Therefore, we evaluated the in-silico interaction between antidepressants and the allosteric site of the P2X7 receptor. This finding reinforces the functional data in the literature that point to the inhibition of the P2X7 receptor. The molecular docking results showed that drugs containing the amino acids TYR295 and PHE95 are essential for a good interaction with the P2X7 receptor at its allosteric site. Furthermore, this study demonstrated that combining antidepressants with p2x7 receptor antagonists can attenuate neuroinflammation.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"595 ","pages":"Pages 130-137"},"PeriodicalIF":2.8,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between body roundness index and stroke: a cross-sectional study based on representative populations from the US and the UK","authors":"Ning Li,&nbsp;Jiwei Sun,&nbsp;Yesen Zhang,&nbsp;Yi Han","doi":"10.1016/j.neuroscience.2026.01.002","DOIUrl":"10.1016/j.neuroscience.2026.01.002","url":null,"abstract":"<div><div>Previous studies had confirmed an association between Body Roundness Index (BRI) and stroke, but it remains unclear whether this association holds across different countries and populations. This study aimed to investigate the association between BRI and stroke across different national cohorts. Data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 and the English Longitudinal Study of Aging (ELSA) from 2012 to 2013, and multifactorial logistic regression models were used to assess the relationship between BRI and stroke. Moreover, restricted cubic spline (RCS) analysis, subgroup analysis, and Receiver Operating Curves (ROC) were also used. The study indicated that higher BRI levels were significantly associated with stroke. Participants in the highest BRI quartile (Q4) had a significantly association with stroke compared to those in the lowest quartile (Q1). ROC indicated that BRI demonstrated superior capability in identifying stroke compared to traditional indicators. Our findings implied that association between BRI and stroke validated in two independent national samples from the US and the UK, suggesting that BRI may have cross-national applicability as a stroke risk biomarker.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"595 ","pages":"Pages 196-204"},"PeriodicalIF":2.8,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal brain-wide recordings reveal early neurophysiological alterations in memory-impaired mice","authors":"Abdelrahman B.M. Eldaly ,&nbsp;Stephen K. Agadagba ,&nbsp;Antara Verma ,&nbsp;Kongyan Li ,&nbsp;Lee Wei Lim ,&nbsp;Leanne Lai-Hang Chan","doi":"10.1016/j.neuroscience.2025.12.035","DOIUrl":"10.1016/j.neuroscience.2025.12.035","url":null,"abstract":"<div><div>Scopolamine, a muscarinic receptor antagonist, is widely utilized to pharmacologically model Alzheimer’s disease (AD) due to its ability to mimic cholinergic deficits and induce memory impairments. Despite its common use in investigating behavioral and cognitive impairments in memory deficit animal models, the longitudinal brain-wide electrophysiological alterations associated with scopolamine administration remain largely unexplored. This study integrated electrophysiological and behavioral analyses to investigate scopolamine-induced cognitive deficits in mice. Using a 16-channel intracranial electroencephalography (iEEG) array, we tracked brain-wide oscillatory changes and functional connectivity over 6 weeks during memory task-related and task-free activities. The mouse’s pre-attentive sensory memory was assessed by auditory evoked potentials (AEPs) within the passive oddball mismatch negativity (MMN) paradigm, and the mouse’s spatial working memory was further evaluated using a Y-maze spontaneous alternation task. The auditory MMN responses indicated significant sensory discrimination impairments from Week 2 onward, and spontaneous theta oscillations demonstrated widespread disruptions by Week 3. Concurrently, scopolamine degraded the animal’s Y-maze successful alternation rates. The decline in alternation performance was correlated with the observed electrophysiological alterations, revealing the progressive impact of scopolamine on cognitive and neural functions. Furthermore, this study identified early electrophysiological biomarkers of brain functional network changes associated with memory impairments, in which functional connectivity abnormalities were observed from the first week of scopolamine administration, suggesting they have diagnostic potential in preclinical AD research. By bridging behavioral outcomes with brain-wide iEEG metrics, this work emphasizes the translational relevance of scopolamine models for understanding AD-like pathology and evaluating therapeutic interventions.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"595 ","pages":"Pages 93-111"},"PeriodicalIF":2.8,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}