eNeuro最新文献

{"title":"Melanocortin 4 Receptor-Dependent Mechanism of ACTH in Preventing Anxiety-Like Behaviors and Normalizing Astrocyte Proteins After Early Life Seizures.","authors":"Mohamed R Khalife, Colin Villarin, Juan Manuel Ruiz, Sam A McClelland, Khalil Abed Rabbo, J Matthew Mahoney, Rod C Scott, Amanda E Hernan","doi":"10.1523/ENEURO.0564-24.2025","DOIUrl":"https://doi.org/10.1523/ENEURO.0564-24.2025","url":null,"abstract":"<p><p>Epilepsy, affecting millions globally, often leads to significant cognitive and psychiatric comorbidities, particularly in children. Anxiety and depression are particularly prevalent, with roughly a quarter of pediatric epilepsy patients having a comorbid diagnosis. Current treatments inadequately address these issues. Adrenocorticotropic hormone (ACTH), a melanocortin peptide, has shown promise in mitigating deficits after early life seizures (ELS), potentially through mechanisms beyond its canonical action on melanocortin 2 receptor (MC2R). This study explores the hypothesis that recurrent ELS is associated with long-term anxiety, and that treatment with ACTH can prevent this anxiety through a mechanism that involves melanocortin 4 receptors (MC4R) in the brain. Our findings reveal that ACTH ameliorates anxiety-like behavior associated with ELS, without altering seizure parameters, in wildtype (WT) but not in MC4R knockout (KO) male and female mice. Our findings also show that knocking-in MC4R in either neurons or astrocytes was able to rescue the anxiety-like behavior after ACTH treatment. Further, our results show that ACTH normalizes important astrocytic proteins like Glial Fibrillary Acidic Protein (GFAP) and Aquaporin-4 (AQP4) after ELS. This suggests that ACTH's beneficial effects on anxiety are mediated through MC4R activation in both neuronal and astrocytic populations. This study underscores the therapeutic potential of targeting MC4R as a treatment, highlighting its role in mitigating anxiety-like behaviors associated with ELS.<b>Significance Statement</b> This study reveals a novel mechanism by which ACTH mitigates anxiety-like behaviors and normalizes key astrocyte markers, including GFAP and AQP4, following early life seizures (ELS) in a melanocortin-4 receptor (MC4R) dependent manner. This challenges the notion that ACTH's primary effects are mediated through the melanocortin 2 receptor in the adrenal cortex. This study further shows that ACTH's effects extend beyond seizure control, targeting psychiatric comorbidities, challenging the prevailing assumption that comorbidities are a result of the seizures. These findings not only expand our understanding of ACTH's beneficial effects through MC4R in both neuronal and astrocyte populations, but also suggest new avenues for treating ELS-related comorbidities.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522979","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":"Limiting Hearing Loss in Transgenic Mouse Models.","authors":"Travis A Babola, Naomi Donovan, Sean S Darcy, Catalina D Spjut, Patrick O Kanold","doi":"10.1523/ENEURO.0465-24.2025","DOIUrl":"10.1523/ENEURO.0465-24.2025","url":null,"abstract":"<p><p>Transgenic mice provide unprecedented access to manipulate and visualize neural circuits; however, those on a C57BL/6 background develop progressive hearing loss, significantly confounding systems-level and behavioral analysis. While outbreeding can limit hearing loss, it introduces strain variability and complicates the generation of complex genotypes. Here, we propose an approach to preserve hearing by crossing transgenic mice with congenic B6.CAST-<i>Cdh23^Ahl</i> ⁺ mice, which maintain low-threshold hearing into adulthood. Widefield and two-photon imaging of the auditory cortex revealed that 2.5-month-old C57BL/6 mice exhibit elevated thresholds to high-frequency tones and widespread cortical reorganization, with most neurons responding best to lower frequencies. In contrast, <i>Ahl+</i> C57BL/6 mice exhibited robust neural responses across tested frequencies and sound levels (4-64 kHz, 30-90 dB SPL) and retained low thresholds into adulthood. Our approach offers a cost-effective solution for generating complex genotypes and facilitates more interpretable systems neuroscience research by eliminating confounding effects from hearing loss.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122472","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":"MEDiCINe: Motion Correction for Neural Electrophysiology Recordings.","authors":"Nicholas Watters, Alessio Buccino, Mehrdad Jazayeri","doi":"10.1523/ENEURO.0529-24.2025","DOIUrl":"10.1523/ENEURO.0529-24.2025","url":null,"abstract":"<p><p>Electrophysiology recordings from the brain using laminar multielectrode arrays allow researchers to measure the activity of many neurons simultaneously. However, laminar microelectrode arrays move relative to their surrounding neural tissue for a variety of reasons, such as pulsation, changes in intracranial pressure, and decompression of neural tissue after insertion. Inferring and correcting for this motion stabilizes the recording and is critical to identify and track single neurons across time. Such motion correction is a preprocessing step of standard spike sorting methods. However, estimating motion robustly and accurately in electrophysiology recordings is challenging due to the stochasticity of the neural data. To tackle this problem, we introduce <b>MEDiCINe</b> (<b>M</b>otion <b>E</b>stimation by <b>Di</b>stributional <b>C</b>ontrastive <b>I</b>nference for <b>Ne</b>urophysiology), a novel motion estimation method. We show that MEDiCINe outperforms existing motion estimation methods on an extensive suite of simulated neurophysiology recordings and leads to more accurate spike sorting. We also show that MEDiCINe accurately estimates the motion in primate and rodent electrophysiology recordings with a variety of motion and stability statistics. We open-source MEDiCINe, usage instructions, examples integrating MEDiCINe with common tools for spike-sorting, and data and code for reproducing our results. This open software will enable other researchers to use MEDiCINe to improve spike sorting results and get the most out of their electrophysiology datasets.<b>Significance Statement</b> Recent advances in high-density microelectrode arrays such as Neuropixels have allowed neurophysiologists to record from hundreds of neurons simultaneously. Such data scale necessitates automatic isolation and tracking of individual neurons throughout a recording session, a process called \"spike sorting\". One challenge for automated spike sorting algorithms is relative motion between the electrodes and the brain, which must be corrected to stabilize the recording. We introduce a method for estimating such motion in neural recordings. Our method outperforms existing motion estimation methods and produces more accurate spike sorting on a benchmark of simulated datasets with known ground-truth motion. Our method also performs well on primate neurophysiology datasets. We open-source our method and instructions for integrating it into common spike sorting pipelines.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398628","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":"Post-mortem interval leads to loss of disease-specific signatures in brain tissue.","authors":"Kimberly C Olney, Katelin A Gibson, Mika P Cadiz, Negin Rahimzadeh, Vivek Swarup, John D Fryer","doi":"10.1523/ENEURO.0505-24.2025","DOIUrl":"https://doi.org/10.1523/ENEURO.0505-24.2025","url":null,"abstract":"<p><p>Human brain banks are essential for studying a wide variety of neurological and neurodegenerative diseases, yet the variability in post-mortem interval (PMI)-the time from death to tissue preservation-poses significant challenges due to rapid cellular decomposition, protein alterations, and RNA degradation. Furthermore, the post-mortem transcriptomic alterations occurring within distinct cell types are poorly understood. In this study, we analyzed the effect of a 3-hour post-mortem interval on single-nucleus RNA signatures in the brains of wild-type (WT) and PS19 mice, a common model of tauopathy. We observed that basic quality control metrics (such as the number of genes and reads per cell), total nuclei counts, and RNA integrity number (RIN^e) remained consistent across all samples, regardless of PMI or genotype. However, a 3-hour PMI diminished the number of genes differentially expressed between PS19 and WT mice, suggesting an impact of delayed processing on the detection of disease-specific transcriptomic signatures. When directly comparing 3-hour PMI versus freshly harvested 0-hour mouse brains, we identified genes upregulated in neurons and interneurons involved in DNA repair, immune response, and stress pathways. Furthermore, genes that were altered in non-neuronal cell types at 3-hours versus 0-hour PMI were associated with cell-cell adhesion processes. These findings highlight the effects of PMI on single-nucleus transcriptional changes that may dampen the true changes in cellular states in banked brain tissues.<b>Significance Statement</b> This study investigates how post-mortem interval (PMI)-the time between death and tissue preservation-affects gene expression in brain cell types using single-nucleus RNA sequencing. By comparing brain samples collected immediately and 3 hours post-mortem in mice, we found that PMI can obscure disease-related gene expression changes, especially in neurons. These findings underscore the importance of accounting for PMI in studies of neurodegenerative disease using human brain banks.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522980","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":"Spatiotemporal Clustering of Functional Ultrasound Signals at the Single-Voxel Level.","authors":"Théo Lambert, Hamid Reza Niknejad, Dries Kil, Gabriel Montaldo, Bart Nuttin, Clément Brunner, Alan Urban","doi":"10.1523/ENEURO.0438-24.2025","DOIUrl":"10.1523/ENEURO.0438-24.2025","url":null,"abstract":"<p><p>Functional ultrasound (fUS) imaging is a well-established neuroimaging technology that offers high spatiotemporal resolution and a large field of view. Typical strategies for analyzing fUS data comprise either region-based averaging, typically based on reference atlases, or correlation with experimental events. Nevertheless, these methodologies possess several inherent limitations, including a restricted utilization of the spatial dimension and a pronounced bias influenced by preconceived notions about the recorded activity. In this study, we put forth single-voxel clustering as a third method to address these issues. A comparison was conducted between the three strategies on a typical dataset comprising visually evoked activity in the superior colliculus in awake mice. The application of single-voxel clustering yielded the generation of detailed activity maps, which revealed a consistent layout of activity and a clear separation between hemodynamic responses. This method is best considered as a complement to region-based averaging and correlation. It has direct applicability to challenging contexts, such as paradigm-free analysis on behaving subjects and brain decoding.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370532","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}

{"title":"Multimodal imaging to identify brain markers of human prosocial behavior.","authors":"Toru Ishihara, Hiroki Tanaka, Toko Kiyonari, Tetsuya Matsuda, Haruto Takagishi","doi":"10.1523/ENEURO.0304-24.2025","DOIUrl":"https://doi.org/10.1523/ENEURO.0304-24.2025","url":null,"abstract":"<p><p>How humans achieve such a high degree of prosocial behavior is a subject of considerable interest. Exploration of the neural foundations of human prosociality has garnered significant attention in recent decades. Nevertheless, the neural mechanisms underlying human prosociality remain to be elucidated. To address this knowledge gap, we analyzed multimodal brain imaging data and data from 15 economic games. The results revealed several significant associations between brain characteristics and prosocial behavior, including stronger interhemispheric connectivity and larger corpus callosum volume. Greater functional segregation and integration, alongside fewer myelin maps combined with a thicker cortex, was linked to prosocial behavior, particularly within the social brain regions. The current study demonstrates that these metrics serve as brain markers of human prosocial behavior and provides novel insights into the structural and functional brain basis of human prosocial behavior.<b>Significance Statement</b> The objective of this study was to identify brain markers associated with human prosocial behavior using data from 15 major economic games and multimodal magnetic resonance imaging data. The results of the study suggest that specific brain indicators, including myelin density and resting-state inter-hemispheric functional connectivities, are associated with prosocial behavior. The use of a data-driven approach holds particular significance within the realm of social neuroscience, a field that grapples with a multitude of variables.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514698","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":"Correlated and Anticorrelated Binocular Disparity Modulate GABA+ and Glutamate/glutamine Concentrations in the Human Visual Cortex.","authors":"Jacek Matuszewski, Ivan Alvarez, William T Clarke, Andrew J Parker, Holly Bridge, I Betina Ip","doi":"10.1523/ENEURO.0355-24.2025","DOIUrl":"https://doi.org/10.1523/ENEURO.0355-24.2025","url":null,"abstract":"<p><p>Binocular disparity is used for perception and action in three dimensions. Neurons in the primary visual cortex respond to binocular disparity in random dot patterns, even when the contrast is inverted between eyes (false depth cue). In contrast, neurons in the ventral stream largely cease to respond to false depth cues. This study evaluated whether GABAergic inhibition is involved in suppressing false depth cues in the human ventral visual cortex.We compared GABAergic inhibition (GABA+) and glutamatergic excitation (Glx) during the viewing of correlated and anticorrelated binocular disparity in 18 participants using single voxel proton magnetic-resonance spectroscopy (MRS). Measurements were taken from the early visual cortex (EVC) and the lateral occipital cortex (LO). Three visual conditions were presented per voxel location: correlated binocular disparity; anticorrelated binocular disparity; or a blank grey screen with a fixation cross. To identify differences in neurochemistry, GABA+ or Glx levels were compared across viewing conditions.In EVC, correlated disparity increased Glx over anticorrelated and rest conditions, also mirrored in the Glx/GABA+ ratio. In LO, anticorrelated disparity decreased GABA+ and increased Glx. The Glx/GABA+ ratio showed increased excitatory over inhibitory drive to anticorrelated disparity in LO. Glx during viewing of anticorrelation in LO was predictive of object-selective BOLD-activity in the same region.We provide evidence that early and ventral visual cortices change GABA+ and Glx concentrations during presentation of correlated and anticorrelated disparity, suggesting a contribution of cortical excitation and inhibition to disparity selectivity.<b>Significance Statement</b> The visual system must correctly match elements from the left and right eye for proper reconstruction of binocular depth. At the earliest part of binocular processing, false matches can activate depth detectors, however, the activation to false matches is absent in the ventral visual stream. We tested whether GABAergic inhibition contributes to the suppression of false matches in the ventral stream by measuring GABAergic inhibition and glutamatergic excitation in the human visual cortex during presentation of correct and false matches. Correct matches increased excitation in response in the early visual cortex, and false matches increased excitation and decreased inhibition in the ventral visual cortex. These results suggest a role for excitation and inhibition in distinguishing depth cues for stereoscopic vision.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499869","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":"Mouse Adrenal Macrophages Are Associated with Pre- and Postsynaptic Neuronal Elements and Respond to Multiple Neuromodulators.","authors":"Matthew D Whim","doi":"10.1523/ENEURO.0153-24.2025","DOIUrl":"10.1523/ENEURO.0153-24.2025","url":null,"abstract":"<p><p>The adrenal medulla is packed with chromaffin cells, modified postganglionic sympathetic neurons that secrete the catecholamines, epinephrine and norepinephrine, during the fight-or-flight response. Sometimes overlooked is a population of immune cells that also resides within the gland but whose distribution and function are not clear. Here I examine the location of CD45+ hematopoietic cells in the mouse adrenal medulla and show the majority are F4/80+/Lyz2+ macrophages. These cells are present from early postnatal development and widely distributed. Anatomically they are associated with chromaffin cells, found aligned alongside synapsin-IR neuronal varicosities and juxtaposed to CD31-IR blood vessels. Using Lyz2cre-GCaMP6f mice to quantify calcium signaling in macrophages revealed these cells respond directly and indirectly to a wide variety of neuromodulators, including pre- and postganglionic transmitters and systemic hormones. Purinergic agonists, histamine, acetylcholine, and bradykinin rapidly and reversibly increased intracellular calcium. These results are consistent with a substantial resident population of innate immune cells in the adrenal medulla. Their close association with chromaffin cells and the preganglionic input suggests they may regulate sympatho-adrenal activity and thus the strength of the fight-or-flight response.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11856350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122475","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}

{"title":"Continuous auditory feedback promotes fine motor skill learning in mice.","authors":"Dongsheng Xiao, Matilde Balbi","doi":"10.1523/ENEURO.0008-25.2025","DOIUrl":"https://doi.org/10.1523/ENEURO.0008-25.2025","url":null,"abstract":"<p><p>Motor skill learning enables organisms to interact effectively with their environment, relying on neural mechanisms that integrate sensory feedback with motor output. While sensory feedback, such as auditory cues linked to motor actions, enhances motor performance in humans, its mechanism of action is poorly understood. Developing a reliable animal model of augmented motor skill learning is crucial to begin dissects the biological systems that underpin this enhancement. We hypothesized that continuous auditory feedback during a motor task would promote complex motor skill acquisition in mice. We developed a closed-loop system using DeepLabCut for real-time markerless tracking of mouse forepaw movements with high processing speed and low latency. By encoding forepaw movements into auditory tones of different frequencies, mice received continuous auditory feedback during a reaching task requiring vertical displacement of the left forepaw to a target. Adult mice were trained over four days with either auditory feedback or no feedback. Mice receiving auditory feedback exhibited significantly enhanced motor skill learning compared to controls. Clustering analysis of reaching trajectories showed that auditory feedback mice established consistent reaching trajectories by Day 2 of motor training. These findings demonstrate that real-time, movement-coded auditory feedback effectively promotes motor skill learning in mice. This closed-loop system, leveraging advanced machine learning and real-time tracking, offers new avenues for exploring motor control mechanisms and developing therapeutic strategies for motor disorders through augmented sensory feedback.<b>Significance Statement</b> Enhancing motor skill learning can greatly improve therapeutic options for patients suffering from motor disorders. Our study demonstrates that continuous, movement-coded auditory feedback markedly accelerates complex motor skill acquisition in mice. By providing real-time auditory cues linked to specific forepaw movements through a closed-loop system-without the need for invasive markers-this approach offers a novel method for investigating the neural mechanisms of motor learning in neuroscience. It also opens new avenues for developing therapeutic strategies for motor function rehabilitation.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499866","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":"Semicircular canals input can modify the fast-phase nystagmus in off-vertical axis rotation of mice.","authors":"Shijie Xiao, Tong Zhao, Wenda Liu, Zihao Peng, Fangyi Chen","doi":"10.1523/ENEURO.0461-24.2025","DOIUrl":"https://doi.org/10.1523/ENEURO.0461-24.2025","url":null,"abstract":"<p><p>Vestibular research is essential for understanding and treating disorders such as vertigo and Meniere's disease. The vestibulo-ocular reflex (VOR) is a key method for assessing vestibular function and an essential tool for diagnosing vertigo. Traditionally, the VOR comprises angular VOR (aVOR) and translational VOR (tVOR), which originate from the vestibular semicircular canals (SCCs) and otolith organs, respectively. VOR consists of both fast-phase and slow-phase eye movements, which functionally interact to contribute to gaze control. However, to calculate the gain and phase parameters of the VOR, it is common practice to exclude fast-phase information superimposed on slow-phase eye movements. As a result, the information contained in the fast phase has not been fully utilized. OVAR is primarily used to evaluate otolith function, as there is no SCC input during its steady state. It is widely accepted that fast-phase nystagmus (FPN) during OVAR is generated by periodic otolith inputs via the central vestibular velocity storage mechanism (VSM). Surprisingly, we discovered in this study that SCC input can modify the generation of FPN in mouse OVAR test, as demonstrated by testing <i>Zpld1</i> (Zona pellucida-like domain containing 1 protein) mutant mice with SCC deficits. This finding was further confirmed using both unilateral and bilateral semicircular canals dehiscence (SCD) surgical models. In addition to revealing the dependence of FPN on SCC input, we demonstrated that FPN can be used to evaluate vestibular function, particularly in conditions that are difficult to assess using slow-phase eye movements, such as unilateral vestibular lesions (UVL) and central modulation via Baclofen treatment.<b>Significance statement</b> Although the SCC input is absent during the steady state of OVAR test, we discovered that SCC input can modify the generation of fast-phase nystagmus (FPN) in mice. This was demonstrated using <i>Zpld1</i> mutant mice with SCC deficits and further confirmed through semicircular canal dehiscence (SCD) models. Additionally, we found that FPN is valuable for assessing vestibular function in conditions such as unilateral vestibular lesions (UVL) and in cases of central modulation by Baclofen, making it a promising diagnostic tool for vestibular clinics.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491326","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}