{"title":"Characterization of Optimal Optogenetic Stimulation Paradigms to Evoke Calcium Events in Cortical Astrocytes.","authors":"Lakshmini Balachandar, Carolina Moncion, Alejandro Suarez, Jorge Riera Diaz","doi":"10.1523/ENEURO.0220-25.2025","DOIUrl":"10.1523/ENEURO.0220-25.2025","url":null,"abstract":"<p><p>Understanding the roles of astrocytic calcium signaling in multiple brain regulatory mechanisms including metabolism, blood flow, neuromodulation, and neuroinflammation has remained one of the enduring challenges in glial biology. To delineate astrocytic contribution from concurrent neuronal activity, it is vital to establish robust control and manipulate astrocytes using a technique like optogenetics due to its high cellular specificity and temporal resolution. The lack of an experimental paradigm to induce controlled calcium signaling in astrocytes has hindered progress in the field. To address this, in this study, we systematically characterize and identify light stimulation paradigms for inducing regulated, on-demand increases in astrocytic calcium in acute brain slice cortical astrocytes from MlC1-ChR2(C128S)-EYFP mice (of either sex). We identified paradigms 20, 40 and 60% (of <i>T</i> = 100 s) to elicit robust calcium responses upon periodic stimulations, while the 95% paradigm exhibited a response only during the first stimulation. We also quantified several parameters, including peak height, full-width at half-maximum (FWHM), and latencies, and observe that the 20% paradigm/duty cycle has the highest peak Δ<i>F</i>/<i>F</i> <sub>0</sub> among the paradigms across all stimulations and the lowest FWHM during the first stimulation. To illustrate the impact of our study, we observed robust changes in cerebral blood flow, because of 20% optogenetic stimulation, in vivo, using laser Doppler flowmetry. Overall, the 20% paradigm is a favorable choice for eliciting robust astrocytic calcium responses in astrocytes while performing periodic stimulations.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12440239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
eNeuroPub Date : 2025-09-12Print Date: 2025-09-01DOI: 10.1523/ENEURO.0034-25.2025
Ryan J Tomm, Brandon J Forys, Liz Kalenteridis, Ian D Daly, Alex R Terpstra, Luke Clark, Stan B Floresco, Trisha Chakrabarty, Rebecca M Todd
{"title":"Depression Levels Are Associated with Reduced Capacity to Learn to Actively Avoid Aversive Events in Young Adults.","authors":"Ryan J Tomm, Brandon J Forys, Liz Kalenteridis, Ian D Daly, Alex R Terpstra, Luke Clark, Stan B Floresco, Trisha Chakrabarty, Rebecca M Todd","doi":"10.1523/ENEURO.0034-25.2025","DOIUrl":"10.1523/ENEURO.0034-25.2025","url":null,"abstract":"<p><p>Depression and anxiety are often characterized by altered reward-seeking and avoidance, respectively. Yet less is known about the relationship between depressive symptoms and specific avoidance behaviors. To address this gap, we conducted two studies. In Study 1, undergraduates and online workers completed an uninstructed go/no-go avoidance task (<i>N</i> <sub>Total</sub> = 465) as a reverse translation of a rodent paradigm. Participants exhibited a wide range of symptom scores on the Beck Depression Inventory-II (BDI-II), ranging from low to severe. In Study 1, cues were used to signal the response type (go/active vs no-go/inhibitory) required to avoid an aversive sound. Higher depressive scores were associated with poorer acquisition of active avoidance in undergraduates. Overall participants showed lower accuracy for active than inhibitory avoidance. To examine whether the better no-go trial performance reflected a prepotent response to avoid aversive outcomes, in Study 2, undergraduates (<i>N</i> <sub>Total</sub> = 330) completed a version of the task that included reward-seeking. Here all participants showed higher accuracy for active reward-seeking and inhibitory avoidance, consistent with a prepotent response to inhibit action to avoid aversive consequences. These findings suggest that in young adults, depressive symptoms are associated with difficulty in overriding prepotent responses to actively avoid aversive outcomes in the absence of reward. This work bridges the gap between preclinical animal models and clinical research, offering insights that could guide the development of more targeted clinical interventions.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
eNeuroPub Date : 2025-09-12DOI: 10.1523/ENEURO.0155-25.2025
Quentin Moreau, Vincent Chamberland, Lisane Moses, Gabriela Milanova, Guillaume Dumas
{"title":"Online HD-tRNS over the right temporoparietal junction modulates social inference but not motor coordination.","authors":"Quentin Moreau, Vincent Chamberland, Lisane Moses, Gabriela Milanova, Guillaume Dumas","doi":"10.1523/ENEURO.0155-25.2025","DOIUrl":"https://doi.org/10.1523/ENEURO.0155-25.2025","url":null,"abstract":"<p><p>Social interactions are fundamental to human cognition, with the right temporoparietal junction (rTPJ) playing a key role in integrating motor coordination and social inference. While transcranial random noise stimulation (tRNS) is a promising technique for modulating cortical excitability in real time, its effect on dynamic social processes remains largely unexplored. This study applied high-definition tRNS (HD-tRNS) over the rTPJ during interaction with an adaptive virtual partner to modulate motor coordination and social inference. Eighty neurotypical adults (49 female) were assigned to one of two experiments: (Exp1) a block design with randomized active and sham stimulation blocks, or (Exp2) a trial-by-trial design with intermixed stimulation protocols. Participants performed a coordination task with a covert virtual partner programmed to behave cooperatively or competitively. Kinematic data and self-reported attributions of humanness and cooperativeness were analyzed. The results showed that HD-tRNS over the rTPJ did not affect motor coordination or overall task performance in either experiment. However, in Exp1, active stimulation progressively reduced attributed humanness and cooperativeness towards the competitive virtual partner, suggesting enhanced detection of antagonistic intent. This gradual modulation of social inference was absent in Exp2, where frequent protocol switching likely disrupted the buildup of stimulation effects. Together, these findings highlight the rTPJ's causal role in self-other distinction, underscore the importance of stimulation protocol design in shaping social cognition, and support the exploration of targeted neuromodulation in clinical and developmental populations with atypical social cognition.<b>Significance statement</b> Social interactions rely on our ability to infer others' intentions, including distinguishing between cooperative and competitive behavior: a process involving the right temporoparietal junction (rTPJ). Here, we used high-definition transcranial random noise stimulation (HD-tRNS) to test the rTPJ's causal role during live social interactions with an adaptive virtual partner. While stimulation did not affect motor coordination, repeated application led participants to gradually attribute less humanness and cooperativeness to a covertly competitive partner, suggesting enhanced sensitivity to competitive intent. These findings provide new insights into the rTPJ's contribution to self-other distinction, demonstrate the potential of HD-tRNS to investigate and modulate social inference, and have implications for understanding and potentially addressing social difficulties in conditions such as autism and schizophrenia.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052552","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}
eNeuroPub Date : 2025-09-12Print Date: 2025-09-01DOI: 10.1523/ENEURO.0297-25.2025
Elijah C Grablin, Joaquin E Douton, Regina M Carelli
{"title":"High Gamma Activity in the Infralimbic Cortex to Nucleus Accumbens Shell Pathway Modulates Innate Aversion Differentially across Sex.","authors":"Elijah C Grablin, Joaquin E Douton, Regina M Carelli","doi":"10.1523/ENEURO.0297-25.2025","DOIUrl":"10.1523/ENEURO.0297-25.2025","url":null,"abstract":"<p><p>Aversion modulation is a key component of hedonic processing, and its dysfunction is evident in psychiatric illnesses. The infralimbic cortex (IL) to nucleus accumbens shell (NAcSh) pathway is essential in hedonic processing in rodents but operates differentially across sex, with beta (20 Hz) oscillatory activity involved in learned aversion in male but not female rats. In this study, we used taste reactivity (TR) and electrophysiology to examine the role of high gamma (80 Hz) activity in affect modulation, specifically innate (quinine) and learned (conditioned taste aversion, CTA) aversion, in male and female Sprague Dawley rats. Local field potential (LFP) recordings in males showed no changes in IL or NAcSh activity, or in IL→NAcSh functional connectivity, in the high gamma frequency band during innate or learned aversion. In contrast, in females, quinine elicited an increase in IL and NAcSh 80 Hz LFP activity and IL→NAcSh functional connectivity. Interestingly, LFP directionality analyses in females indicated that top-down modulation from IL to NAcSh was associated with innate aversive behavior expression. To confirm a causal link of 80 Hz activity in aversion processing in females, optogenetics was used. Here, optogenetic stimulation of the IL→NAcSh pathway did not affect learned (CTA) aversion but it selectively decreased innate (quinine) aversion. Collectively, these results highlight sex- and frequency-specific differences in aversion modulation by the IL→NAcSh pathway, with high gamma frequencies involved in modulating innate aversion, specifically in female rats.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
eNeuroPub Date : 2025-09-12Print Date: 2025-09-01DOI: 10.1523/ENEURO.0207-25.2025
Michelle R Doyle, Paola Campo, Selen Dirik, Maria G Balaguer, Angelica R Martinez, Marsida Kallupi, Abraham A Palmer, Giordano de Guglielmo
{"title":"A Preclinical Alcohol Biobank: Samples from Behaviorally Characterized HS Rats for AUD Research.","authors":"Michelle R Doyle, Paola Campo, Selen Dirik, Maria G Balaguer, Angelica R Martinez, Marsida Kallupi, Abraham A Palmer, Giordano de Guglielmo","doi":"10.1523/ENEURO.0207-25.2025","DOIUrl":"10.1523/ENEURO.0207-25.2025","url":null,"abstract":"<p><p>Alcohol use disorder (AUD) imposes a significant global health burden, yet effective treatments remain limited. There are no well-characterized, AUD-relevant, rodent biological sample repositories to support research in this area. To address this gap, we established the Alcohol Biobank, a comprehensive resource containing thousands of samples from over 700 (half males, half females) genetically diverse heterogeneous stock (HS) rats. Modeled after two successful cocaine and oxycodone biobanks, this repository uses the chronic intermittent ethanol vapor exposure (CIE) model, paired with oral self-administration, to characterize AUD-like behaviors, including ethanol consumption, preference, motivation, and withdrawal symptoms such as allodynia and anxiety-like behavior. Longitudinal samples (blood, urine, and feces) are collected before, during, and after ethanol exposure, while tissue samples (brain, heart, kidneys, liver, cecum, reproductive organs, adrenal glands, blood) are obtained at intoxication, acute withdrawal, protracted abstinence, or from naive controls. Samples are preserved via snap-freezing or paraformaldehyde fixation to support diverse applications, including genomics, transcriptomics, proteomics, and neuroanatomy. Samples are freely available to nonprofit organizations at www.alcoholbiobank.org Genetic and behavioral data about these rats are deposited in public repositories. The Alcohol Biobank facilitates collaborative research to uncover biomarkers and develop novel therapies for AUD, addressing a critical need in addiction science.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":"12 9","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
eNeuroPub Date : 2025-09-10Print Date: 2025-09-01DOI: 10.1523/ENEURO.0044-25.2025
Ruth M Shontell, David Araki, Kendra M Ormsbee, Donovan D Delgado, Robert A Nichols
{"title":"The Beta Amyloid Core Hexapeptide Protects against Full-Length Beta Amyloid-Induced Alteration of Dendritic Spine Morphology and Density.","authors":"Ruth M Shontell, David Araki, Kendra M Ormsbee, Donovan D Delgado, Robert A Nichols","doi":"10.1523/ENEURO.0044-25.2025","DOIUrl":"10.1523/ENEURO.0044-25.2025","url":null,"abstract":"<p><p>Pathological levels of beta amyloid (Aβ) lead to disruption and elimination of synapses in brain as the result of direct neurotoxicity as well as neuroinflammation. The synaptic impact of beta amyloid includes altered morphology and reduced number of dendritic spines at excitatory synapses, evident in the brains of individuals with Alzheimer's disease. Here, we assessed the ability of an identified neuroprotective peptide, YEVHHQ, derived from the N-terminal domain of Aβ, known as the AβCore, to protect against Aβ-induced alterations in dendritic spines. Our approach involved both 2D and 3D imaging of spine morphology in hippocampal neuron cultures from mice of either sex, with the 3D imaging focusing on the postsynaptic density (PSD), as its morphology is tightly correlated with synaptic strength, and presynaptic terminal morphology and density to assess the impact on both sides of the synapse. We present evidence for uniform prevention by the AβCore of Aβ-induced reductions in spine cross-sectional size and density as well as PSD surface area and volume. In addition, the AβCore alone increased the presynaptic terminal volume in parallel to the reversal of Aβ-induced changes in spine and PSD size. Together, these results provide support for reversal of structural changes underlying the functional reversal by the AβCore of Aβ-induced impairment of synaptic dynamics.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
eNeuroPub Date : 2025-09-10Print Date: 2025-09-01DOI: 10.1523/ENEURO.0059-25.2025
Khalin E Nisbett, George F Koob
{"title":"Neuronal Colocalization of μ-Opioid Receptor, κ-Opioid Receptor, and Oxytocin Receptor mRNA in the Central Nucleus of the Amygdala in Male and Female Mice.","authors":"Khalin E Nisbett, George F Koob","doi":"10.1523/ENEURO.0059-25.2025","DOIUrl":"10.1523/ENEURO.0059-25.2025","url":null,"abstract":"<p><p>Given the observed interaction and reports of oxytocin, μ-opioid receptor, or κ-opioid receptor expression in brain regions important to emotion regulation (i.e., the central amygdala), we hypothesized that oxytocin (<i>oxtr</i>), μ-opioid (<i>oprm1</i>), and κ-opioid (<i>oprk1</i>) receptor mRNA were colocalized to the same cells in the central amygdala. RNAscope in situ hybridization performed on fresh-frozen coronal brain sections was used to label cells containing <i>oxtr</i>, <i>oprm1</i>, and/or <i>oprk1</i> The coronal sections were imaged using a 40× objective (widefield fluorescence) on a Leica Thunder fluorescent microscope, and the images were processed using open-source ImageJ/Fiji software and analyzed using the Imaris software. The central amygdala was identified using Paxinos and Watson's <i>The Mouse Brain in Stereotaxic Coordinates</i> ( Paxinos and Franklin, 2019). Eight distinct cell populations were enumerated (i.e., <i>oxtr</i>-only, <i>oprm1</i>-only, <i>oprk1</i>-only, <i>oxtr</i> + <i>oprm1</i>-only, <i>oxtr</i> + <i>oprk1</i>-only, <i>oprm1</i> + <i>oprk1</i>-only, <i>oxtr</i> + <i>oprm1</i> + <i>oprk1</i>, and nontranscript cells). Our findings demonstrated that 47% of cells in the central amygdala express <i>oxtr</i> with <i>oprm1</i> and/or <i>oprk1</i> Of the <i>oxtr</i>-expressing cells, 38% colocalized only <i>oprm1</i>, and 56% of <i>oxtr</i>-expressing cells colocalized both <i>oprm1</i> and <i>oprk1</i> However, 53% of <i>oprm1</i>-expressing cells colocalized <i>oxtr</i>, and 61% of <i>oprk1</i>-expressiong cells colocalized <i>oxtr</i> These findings suggest that opioid and oxytocin receptors can function at the cellular level through morphological interactions. Future work will examine the physiological basis for the interaction between opioid and oxytocin receptors using transgenic behavior and electrophysiological assays.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
eNeuroPub Date : 2025-09-08Print Date: 2025-09-01DOI: 10.1523/ENEURO.0589-24.2025
Jake Lustig, Alexander Lammers, Julia Kaiser, Payal Patel, Aidan Raghu, James M Conner, Phong Nguyen, Eiman Azim, Vibhu Sahni
{"title":"Selective Targeting of a Defined Subpopulation of Corticospinal Neurons Using a Novel Klhl14-Cre Mouse Line Enables Molecular and Anatomical Investigations through Development into Maturity.","authors":"Jake Lustig, Alexander Lammers, Julia Kaiser, Payal Patel, Aidan Raghu, James M Conner, Phong Nguyen, Eiman Azim, Vibhu Sahni","doi":"10.1523/ENEURO.0589-24.2025","DOIUrl":"10.1523/ENEURO.0589-24.2025","url":null,"abstract":"<p><p>The corticospinal tract (CST) facilitates skilled, precise movements, which necessitates that subcerebral projection neurons (SCPNs) establish segmentally specific connectivity with brainstem and spinal circuits. Developmental molecular delineation enables prospective identification of corticospinal neurons (CSNs) projecting to thoraco-lumbar spinal segments; however, it remains unclear whether other SCPN subpopulations in developing sensorimotor cortex can be prospectively identified in this manner. Such molecular tools could enable investigations of SCPN circuitry with precision and specificity. During development, Kelch-like 14 (<i>Klhl14</i>) is specifically expressed by a specific SCPN subpopulation, CSN<sub>BC-lat</sub>, that reside in lateral sensorimotor cortex with axonal projections exclusively to bulbar-cervical targets. In this study, we generated Klhl14-T2A-Cre knock-in mice to investigate SCPN that are <i>Klhl14+</i> during development into maturity. Using conditional anterograde and retrograde labeling in mice of either sex, we find that Klhl14-Cre is specifically expressed by CSN<sub>BC-lat</sub> only at specific developmental time points. We establish conditional viral labeling in Klhl14-T2A-Cre mice as a new approach to reliably investigate CSN<sub>BC-lat</sub> axon targeting and confirm that this identifies known molecular regulators of CSN axon targeting. Therefore, Klhl14-T2A-Cre mice can be used as a novel tool for identifying molecular regulators of CST axon guidance in a relatively high-throughput manner in vivo. Finally, we demonstrate that intersectional viral labeling enables precise targeting of only Klhl14-Cre+ CSN<sub>BC-lat</sub> in the adult central nervous system. Together, our results establish that developmental molecular delineation of SCPN subpopulations can be used to selectively and specifically investigate their development, as well as anatomical and functional organization into maturity.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
eNeuroPub Date : 2025-09-04Print Date: 2025-09-01DOI: 10.1523/ENEURO.0586-24.2025
Lan Zhang, Xiao-Wei Pang, Lu-Yang Zhang, Li-Fang Zhu, Wan-Ning Li, Yun-Hui Chu, Luo-Qi Zhou, Dai-Shi Tian, Chuan Qin, Lian Chen
{"title":"Gut Microbiota and White Matter Integrity: A Two-Sample Mendelian Randomization Analysis.","authors":"Lan Zhang, Xiao-Wei Pang, Lu-Yang Zhang, Li-Fang Zhu, Wan-Ning Li, Yun-Hui Chu, Luo-Qi Zhou, Dai-Shi Tian, Chuan Qin, Lian Chen","doi":"10.1523/ENEURO.0586-24.2025","DOIUrl":"10.1523/ENEURO.0586-24.2025","url":null,"abstract":"<p><p>The causal relationship between gut microbiota (GM) and white matter injury and communication remains unclear. We aimed to scrutinize the plausible causal impact of GM on white matter hyperintensities (WMHs), white matter microstructure, white matter connectivity, and multiple neurological diseases via Mendelian randomization study. We identified four WMH-related bacterial taxa, including class <i>Melainabacteria</i>, order <i>Gastranaerophilales</i>, family <i>Alcaligenaceae</i>, and genus <i>Ruminiclostridium 6</i> In addition, three bacterial taxa were discovered that have consistent effect on multiple aspects of white matter microstructure. Furthermore, we found 12 strong associations between genetic liability in GM and white matter connectivity. Among these bacterial taxa, the family <i>Clostridiaceae 1</i> demonstrated a protective effect against ischemic stroke (IS). The genus <i>Barnesiella</i> showed protective effect on IS and small vessel stroke while posed a risk effect on neuromyelitis optica spectrum disorder (NMOSD), as well as on aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD). The order <i>Desulfovibrionales</i> and family <i>Desulfovibrionaceae</i> showed protective effect against cardioembolic stroke, and the genus <i>Ruminococcus gnavus group</i> showed a protective effect on amyotrophic lateral sclerosis. In terms of the mapped genes of statistically significant bacterial taxa, genes such as <i>CPNE1</i>, <i>PIGU</i>, <i>MED22</i>, <i>SURF6</i>, <i>DOCK10</i>, and <i>COPS3</i> exhibited a significant causal correlation with the corresponding white matter connectivity. This study demonstrated a genetically predicted causal relationship between GM and WMH, white matter microstructure, white matter connectivity, and multiple neurological diseases, based on GWAS data from mixed-sex cohorts without sex-stratified summary statistics. These findings highlight the potential role of GM in influencing brain structural integrity.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
eNeuroPub Date : 2025-09-03Print Date: 2025-09-01DOI: 10.1523/ENEURO.0573-24.2025
Debora Nolte, Vincent Schmidt, Aitana Grasso-Cladera, Peter König
{"title":"Investigating Saccade-Onset Locked EEG Signatures of Face Perception during Free-Viewing in a Naturalistic Virtual Environment.","authors":"Debora Nolte, Vincent Schmidt, Aitana Grasso-Cladera, Peter König","doi":"10.1523/ENEURO.0573-24.2025","DOIUrl":"10.1523/ENEURO.0573-24.2025","url":null,"abstract":"<p><p>Current research strives to investigate cognitive processes under natural conditions. Virtual reality and EEG are promising techniques combining naturalistic settings with close experimental control. However, many questions and technical challenges remain, e.g., are saccade onsets a suitable replacement of fixation onsets as key events in continuous gaze trajectories ( Amme et al., 2024), and consequently, can VR capture differences across different stimulus categories associated with varying saccade durations? To address both questions, we investigate the N170 face effect in humans (14 males, 19 females, zero diverse) using a free-viewing and free-movement immersive VR study that contained houses, various background stimuli, and, notably, static and moving pedestrians to study face perception under naturalistic conditions. Our results show that aligning trials to saccade onsets leads to more well-defined ERPs than fixation onsets, especially for the P100 component, demonstrating that saccade-onset ERPs are a better-suited analysis method for this type of experiment. Furthermore, we observe an evolution of category-based differences, i.e., face versus background saccade-onset ERPs, compatible with previous reports but extending in a large temporal window and including all electrode sites at different points in time. In summary, employing VR, EEG, and eye-tracking to investigate differences across fixation categories provides insights into the relevance of saccadic onsets as event triggers and enhances our understanding of cognitive processes in naturalistic settings.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":"12 9","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}