Journal of Neuroscience最新文献

{"title":"Linking connectivity dynamics to symptom severity and cognitive abilities in children with autism spectrum disorder: An fNIRS study.","authors":"Conghui Su,Yubin Hu,Yifan Liu,Ningxuan Zhang,Liming Tan,Shuiqun Zhang,Aiwen Yi,Yaqiong Xiao","doi":"10.1523/jneurosci.0161-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.0161-25.2025","url":null,"abstract":"Functional near-infrared spectroscopy (fNIRS) has emerged as a valuable tool for investigating neurobiological markers in children with autism spectrum disorder (ASD). While previous studies have identified abnormal functional connectivity in ASD children compared to typically developing (TD) peers, brain connectivity dynamics and their associations with autism symptoms and cognitive abilities remain underexplored. We analyzed fNIRS data from 44 children (30 boys, 21 ASD/23 TD) aged 2.08-6.67 years while they viewed a silent cartoon. Using sliding window correlation and k-means clustering, we assessed group differences in dynamic connectivity and the correlations with symptom severity and cognitive performance. Our results revealed that children with ASD showed reduced dwell time in a specific brain state and fewer state transitions compared to TD children. These atypical brain state patterns were negatively correlated with autism symptom severity and positively correlated with adaptive behavior and cognitive performance across participants. Mediation analysis revealed that adaptive behavior fully mediated the relationship between brain dynamics and cognitive performance. Furthermore, dynamic connectivity features achieved 74.4% accuracy in distinguishing ASD from TD children. Importantly, the link between brain dynamics and cognitive performance was replicated in an independent TD sample, underscoring the robustness of this finding. Together, these findings highlight altered brain dynamics in young children with ASD and underscore the critical role of adaptive behavior in bridging neural activity and cognitive performance. These insights advance our understanding of neural mechanisms underlying ASD and point to potential pathways for early interventions and clinical applications.Significant statement The brain dynamics and their relationships with symptom severity and cognitive abilities in children with autism spectrum disorder (ASD) remain poorly understood. Using dynamic functional connectivity analysis, our study identified distinct brain state patterns in children with ASD. These patterns were associated with both autism symptom severity and cognitive performance. Importantly, adaptive behavior emerged as a crucial mediator between brain dynamics and cognitive function. Our findings provide novel insights into the neural mechanisms of ASD and highlight the critical role of adaptive behavior in formulating future intervention strategies. By linking specific neural dynamics to adaptive behaviors and cognitive abilities, our study enhances our understanding of ASD neurobiology and has the potential to improve outcomes for affected children.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"17 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Noninvasive Biomarkers for Assessing the Excitatory/Inhibitory Imbalance in Children with Epilepsy.","authors":"Sakar Rijal,F Kathryn King,Hmayag Partamian,Saeed Jahromi,M Scott Perry,Crystal Cooper,Christos Papadelis","doi":"10.1523/jneurosci.0520-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.0520-25.2025","url":null,"abstract":"Epileptic seizures involve a cortical excitation-inhibition imbalance driven by dysfunctional interneurons that contribute to gamma oscillations generation. While impaired gamma oscillations are commonly reported in epilepsy, the dynamics of broadband and narrowband gamma as well as beta oscillations remain underexplored. These oscillations may serve as noninvasive electrophysiological markers associated with altered cortical dynamics, potentially reflecting underlying excitation-inhibition imbalance in epilepsy. Here, we recorded high-density electroencephalography and magnetoencephalography data to investigate visual stimuli-elicited cortical oscillations in 48 neurotypical (20 females) and 49 children (26 females) with epilepsy. We found that epilepsy is characterized by reduced amplitude and prolonged latency of evoked cortical response compared to controls after visual stimulation, with alterations in N1 peaks, and M100, M150, and M250 components (p<0.05). Additionally, source imaging revealed disrupted oscillatory features in epilepsy patients, including suppressed power, reduced amplitude, and increased latency in evoked and induced beta and gamma oscillations from the visual cortex (p<0.05). These alterations were consistent across diverse epilepsy subtypes, including focal, generalized, and non-lesional epilepsy cases. Utilizing these differences, we developed a novel classification model that differentiates individuals with epilepsy from controls with high accuracy, offering potential clinical utility in epilepsy diagnosis. Our results suggest that disrupted beta and gamma oscillations may be associated with impaired inhibitory mechanisms and altered cortical dynamics, potentially indicative of an excitation-inhibition imbalance. Our findings highlight the potential of noninvasive electrophysiological biomarkers to capture cortical dynamics possibly influenced by excitation-inhibition imbalance in epilepsy, supporting their use in early diagnosis and disease monitoring.Significance Statement Diagnosing pediatric epilepsy is challenging as seizures often manifest subtly or mimic benign behaviors, complicating electroencephalogram interpretation. This underscores the need for noninvasive neurophysiological markers that can characterize cortical dysfunction. Excitation-inhibition imbalance is widely recognized as a key mechanism in the pathophysiology of epilepsy, with substantial evidence linking it to cortical gamma oscillations. Here, we identified consistent alterations in visually evoked and induced beta and gamma oscillations in children with epilepsy, which possibly reflect disturbances in inhibitory control and broader disruptions in cortical network dynamics. Features derived from these oscillations distinguished epilepsy from controls with good accuracy. These findings indicate that visual stimulus-related electrophysiological features are promising biomarkers for assisting early diagnosis and tracking disease progression in pedi","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"42 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tonic GABA and Glycine Inhibition Control Pain Hypersensitivity via Limiting α2δ-1- and mGluR5-Dependent NMDA Receptor Activity at Primary Afferent-Excitatory Neuron Synapses.","authors":"Yuying Huang 黄玉莹,Hong Chen 陈红,Shao-Rui Chen 陈少瑞,Hui-Lin Pan 潘惠麟","doi":"10.1523/jneurosci.1469-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.1469-25.2025","url":null,"abstract":"Impaired synaptic inhibition by GABA and glycine contributes to excitatory-inhibitory imbalance in the spinal cord associated with chronic neuropathic pain; however, the underlying mechanisms remain unclear. In this study, we investigated how GABAergic and glycinergic inputs regulate synaptic NMDA receptor (NMDAR) activity in both excitatory and inhibitory neurons of the spinal dorsal horn in male and female mice. Vesicular glutamate transporter-2 (VGluT2)-expressing excitatory neurons and vesicular γ-aminobutyric acid transporter (VGAT)-expressing inhibitory neurons exhibited comparable mixed GABAergic and glycinergic IPSCs. Blockade of GABAA receptors with gabazine or glycine receptors with strychnine potentiated NMDAR-mediated miniature EPSC (mEPSC) frequency, the amplitude of EPSCs monosynaptically evoked from the dorsal root, and puff NMDA currents in VGluT2, but not VGAT, neurons. These effects were abolished by silencing neuronal activity with tetrodotoxin or in Cacna2d1 knockout mice. In mice with conditional Grin1 knockout in primary sensory neurons (Grin1-cKO), gabazine and strychnine did not affect mEPSC frequency but still enhanced puff NMDA currents in dorsal horn neurons. Furthermore, intrathecal gabazine- or strychnine-induced nociceptive hypersensitivity was diminished by Grin1-cKO, Cacna2d1 knockout, or α2δ-1 C-terminus peptide. Additionally, blocking metabotropic glutamate receptor 5 prevents gabazine- and strychnine-induced increases in NMDAR-mediated mEPSC frequency, evoked EPSCs, and puff NMDA currents in VGluT2 neurons as well as nociceptive hypersensitivity. Our findings reveal that normal GABAergic and glycinergic inhibition tonically suppresses both presynaptic and postsynaptic NMDAR activity at primary afferent-excitatory neuron synapses. α2δ-1 and metabotropic glutamate receptor 5 are essential for disinhibition-induced nociceptive hypersensitivity and synaptic NMDAR hyperactivity in the spinal cord.Significance Statement This study identifies for the first time the specific spinal cord neurons and synapses where inhibitory signals-GABA and glycine-normally suppress glutamate NMDA receptor (NMDAR) activity to regulate pain transmission. Loss of this inhibitory control leads to heightened pain sensitivity by selectively increasing presynaptic and postsynaptic NMDAR activity in genetically tagged excitatory neurons. Eliminating NMDARs from primary sensory neurons or blocking two proteins linked to NMDARs-α2δ-1 and mGluR5-markedly reduces this pain hypersensitivity. These findings uncover how disrupted synaptic inhibition drives chronic pain and highlight α2δ-1 and mGluR5 as promising therapeutic targets for restoring excitation-inhibition balance in the spinal cord. This work advances our understanding of key cellular and molecular substrates underlying chronic neuropathic pain.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"39 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct portions of superior temporal sulcus combine auditory representations with different visual streams.","authors":"Gabriel Fajardo,Mengting Fang,Stefano Anzellotti","doi":"10.1523/jneurosci.1188-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.1188-24.2025","url":null,"abstract":"In humans, the superior temporal sulcus (STS) combines auditory and visual information. However, the extent to which it relies on visual information from the ventral or dorsal stream remains uncertain. To address this, we analyzed open-source functional magnetic resonance imaging data collected from 15 participants (6 females and 9 males) as they watched a movie. We used artificial neural networks to investigate the relationship between multivariate response patterns in auditory cortex, the two visual streams, and the rest of the brain, finding that distinct portions of the STS combine information from the two visual streams with auditory information.Significance Statement The STS combines auditory and visual inputs. However, visual information is processed along a ventral and a dorsal stream, and the extent to which these streams contribute to the combination of audio-visual information is poorly understood. Is auditory information combined with visual information from both streams in a single centralized hub? Or do separate regions combine auditory information with ventral visual regions on one hand, and with dorsal visual regions on the other? To address this question, we employed a multivariate connectivity method based on artificial neural networks. Our findings reveal that information from the two visual streams is combined with auditory information in distinct portions of STS, offering new insights into the neural architecture underlying multisensory perception.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"98 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha-band activity tracks reflexive changes in the breadth of the zoom lens of attention.","authors":"Dirk van Moorselaar,Jan Theeuwes,Stefan Van der Stigchel","doi":"10.1523/jneurosci.0706-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.0706-25.2025","url":null,"abstract":"Spatial attention is often conceptualized as a flexible \"zoom lens\" that can dynamically adjust its focus, but most evidence stems from studies of voluntary attention. Our study investigates whether involuntary, reflexive attention exhibits similar adaptability in attentional scope. Using behavioral and electroencephalographic (EEG) experiments with exogenous cues of varying spatial extent, we examined how attentional gradients dynamically adjust when attention is involuntarily captured. Male and female human participants performed visual search tasks preceded by narrow or broad cue displays at different onset asynchronies. We applied inverted encoding models to alpha-band neural activity to precisely track the locus and breadth of attentional tuning. Across experiments, we found that reflexive attentional gradients flexibly adapt to match cue characteristics. Behaviorally, narrow cues yielded progressively sharper attentional gradients compared to broad cues, with differences emerging over time. Critically, EEG analyses revealed that alpha-band activity tracked these dynamic adjustments, with differences in spatial selectivity emerging rapidly (±200 ms post-cue) and continuing to evolve. Contrary to previous suggestions that involuntary attention primarily influences response efficiency, our results demonstrate that exogenous cues modulate attentional resources across the visual field at early processing stages.Significance statement Our study provides novel evidence of the dynamic nature of involuntary, reflexive attention, contributing to an ongoing debate about the mechanisms of exogenous spatial attention. By employing advanced neuroimaging techniques, we demonstrate that attentional gradients can flexibly adapt to cue characteristics, revealing a more nuanced understanding of how attention is allocated during rapid, involuntary shifts of focus. These findings extend the zoom lens model beyond voluntary attention, highlighting the brain's sophisticated mechanisms of spatial attention.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"52 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synaptic properties of layer 6 auditory corticothalamic inputs in normal hearing and noise-induced hearing loss.","authors":"Yanjun Zhao, Brandon Bizup, Thanos Tzounopoulos","doi":"10.1523/JNEUROSCI.2394-24.2025","DOIUrl":"10.1523/JNEUROSCI.2394-24.2025","url":null,"abstract":"<p><p>Layer 6 corticothalamic neurons (CTs) provide strong feedback input that is crucial to perception and cognition in normal and pathological states; however, the synaptic properties of this input remain largely unknown, especially in pathology. Here, we examined the synaptic properties of CT axon terminals in the medial geniculate body (MGB), the auditory thalamus, in normal hearing male and female mice and in a mouse model of noise-induced hearing loss, also in male and female mice. In normal hearing mice, we found that the amplitude of CT-evoked excitatory postsynaptic current (EPSC) to the core-type ventral subdivision of the auditory thalamus (MGv), which mainly conveys rapid sensory information, is larger compared to the amplitude of CT-evoked EPSC to the matrix-type dorsal subdivision of the auditory thalamus (MGd), which likely conveys higher-order internal state information. This is due to higher axonal density and/or axonal recruitment in CT→MGv compared to CT→MGd synapses. After noise trauma, we observed enhanced short-term facilitation in CT→MGd but not CT→MGv synapses. Our findings reveal a previously unknown mechanism of short-term synaptic plasticity after noise-induced hearing loss via which CTs enhance the throughput of matrix-type thalamus, likely to improve perceptual recovery via higher-order contextual modulation.<b>Significance Statement</b> Auditory layer 6 corticothalamic neurons (CTs) send massive projections to the auditory thalamus, the medial geniculate body (MGB). This pathway is crucial for sound perception and cognition. However, the synaptic properties of this pathway under either normal or pathological hearing remain poorly understood. We found enhanced evoked synaptic responses between CT and the ventral (CT→MGv) compared to CT and the dorsal (CT→MGd) MGB subdivision. Importantly, we discovered an enhancement of activity-dependent facilitation at the CT→MGd synapses after noise-induced hearing loss, thus highlighting a plasticity mechanism that might enhance perceptual recovery via higher-order cortico-thalamo-cortical modulation.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rebound bursting selectively enables fast dynamics in dopamine midbrain neurons projecting to the dorso-lateral striatum.","authors":"Strahinja Stojanovic,Christopher J Knowlton,Richard Egger-Mackrodt,Johanna Mankel,Josef Shin,Stephan Lammel,Carmen C Canavier,Jochen Roeper","doi":"10.1523/jneurosci.0361-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.0361-25.2025","url":null,"abstract":"Dopamine midbrain (DA) neurons are involved in a wide array of key brain functions including movement control and reward-based learning. They are also critical for major brain disorders such as Parkinson Disease or schizophrenia. DA neurons projecting to distinct striatal territories are diverse with regards to their molecular makeup and cellular physiology, which are likely to contribute to the observed differences in temporal dopamine dynamics. Among these regions, the dorsolateral striatum (DLS) displays the fastest dopamine dynamics, which might control the moment-to-moment vigor and variability of voluntary movements. However, the underlying mechanisms for these DLS-specific fast DA fluctuations are unresolved. Here, we show that DLS-projecting DA neurons in the substantia nigra (SN) possess a unique biophysical profile allowing immediate 10-fold accelerations in discharge frequency via rebound bursting. By using a combination of in vitro patch-clamp recordings in projection-defined DA SN subpopulations from adult male mice and developing matching projection-specific computational models, we demonstrate that a strong interaction of Cav3 and SK channels specific for DLS-projecting Aldh1a1-positive DA SN (DLS-DA) neurons controls the gain of fast rebound bursting, while Kv4 and HCN channels mediate timing of rebound excitability. In addition, GIRK channels activated by D2- and GABAB-receptors prevent rebound bursting in these DLS-DA neurons. Furthermore, our in vivo patch-clamp recordings and matching in vivo computational models provide evidence that these unique rebound properties might be preserved in the intact brain, where they might endow specific computational properties well suited for the generation of fast dopamine dynamics present in the dorsolateral striatum.Significance Statement DLS-projecting DA neurons in the SN exhibit unique rebound bursting that enables rapid, 10-fold increases in firing frequency. This firing fingerprint is driven by Cav3 and SK channel interactions, modulating burst gain, and fine-tuned by Kv4 and HCN channels controlling rebound timing. GIRK channels, activated by D2- and GABAB-receptors, inhibit this bursting. In vivo patch-clamp recordings provide evidence that these rebound dynamics might be preserved in the intact brain, potentially supporting the fast dopamine fluctuations crucial for controlling movement vigor and variability in the DLS. These findings provide insights into the mechanisms underlying fast DA dynamics and their role in motor function, with implications for brain disorders like Parkinson disease and schizophrenia.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"92 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TREK1 channels shape spindle-like oscillations, neuronal activity, and short-term synaptic plasticity in thalamocortical circuits.","authors":"Afsaneh Labbaf,Valérie Krauth,Nicole Rychlik,Venu Narayanan Naik,Laura Vinnenberg,Elif Karabatak,Audrey Teasley,Paula P Perissinotti,John A White,Sven G Meuth,Gilles van Luijtelaar,Francisco J Urbano,Thomas Budde,Mehrnoush Zobeiri","doi":"10.1523/jneurosci.0432-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.0432-24.2025","url":null,"abstract":"Although TREK1 channels are widely expressed in several thalamic nuclei, the role of this K2P family member in modulating thalamic cell excitability and physiological thalamocortical oscillatory activity is not well studied. Here we explored the contribution of TREK1 channels to membrane properties of two important building blocks of the thalamocortical (TC) system, namely GABAergic neurons of reticular thalamic nucleus (RTN) and TC neurons in different sensory thalamic nuclei including the ventrobasal complex (VB; somatosensory system) and the medial geniculate nucleus (MGN; auditory system), using male TREK1 knock out (TREK1-/-) mice. Furthermore, we show that the loss of TREK1 channels has distinct effects on neuronal function in different thalamic nuclei. Compared to controls, TREK1-/- mice exhibit decreased excitability in RTN neurons, while VB neurons maintain similar excitability levels. Additionally, the absence of TREK1 channels alters the action potential (AP) characteristics in VB TC neurons and affects GABAergic inhibitory tone in RTN neurons. In TREK1-/- mice, the excitability of cortical pyramidal cells is increased. It is tempting to assume that this combination of changes contributes to a high number of sharp, spindle-like oscillations observed in sleep local field potential (LFP) recordings of these mice. In addition, TREK1-/- mice show a lower amount of delta (1-4 Hz) oscillations during slow - wave sleep, and a time-of-day-dependent alteration in the amount of sleep and wakefulness. They also show disturbed auditory signal processing and altered excitability in the auditory thalamus. These findings underline the relevance of TREK1 channels' broad contribution to the thalamus and thalamocortical system.Significance statement Using a genetic knockout approach, we explored TREK1 channels' impact on the thalamocortical system, focusing on the thalamic reticular nucleus (RTN), ventral medial geniculate nucleus (vMGN), and ventrobasal (VB) nuclei. (1) TREK1 loss altered short-term synaptic plasticity. (2) RTN neuron excitability decreased, vMGN activity increased, and VB excitability remained unchanged, suggesting cell-specific roles and compensatory mechanisms. (3) Network changes included modified slow oscillations, abnormal spindle waves, and heightened auditory responses. (4) Behaviorally, TREK1 loss affected NREM sleep and wakefulness duration. These findings highlight TREK1's critical role in thalamic function.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"3 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perisynaptic Astroglial Response to In Vivo Long-Term Potentiation and Concurrent Long-Term Depression in the Hippocampal Dentate Gyrus.","authors":"Andrea J Nam, Masaaki Kuwajima, Patrick H Parker, Jared B Bowden, Wickliffe C Abraham, Kristen M Harris","doi":"10.1523/JNEUROSCI.0943-25.2025","DOIUrl":"10.1523/JNEUROSCI.0943-25.2025","url":null,"abstract":"<p><p>Perisynaptic astroglia provide critical molecular and structural support to regulate synaptic transmission and plasticity in the nanodomain of the axon-spine interface. Three-dimensional reconstruction from serial section electron microscopy (3DEM) was used to investigate relationships between perisynaptic astroglia and dendritic spine synapses undergoing plasticity in the adult hippocampus. Delta-burst stimulation (DBS) of the medial perforant pathway induced long-term potentiation (LTP) in the middle molecular layer and concurrent long-term depression (cLTD) in the outer molecular layer of the dentate gyrus in awake male rats. The contralateral hippocampus received baseline stimulation as a within-animal control. Brains were obtained 30 min or 2 h after DBS onset. An automated 3DEM pipeline was developed to enable unbiased quantification of astroglial coverage at the perimeter of the axon-spine interface. Under all conditions, >85% of synapses had perisynaptic astroglia processes within 120 nm of some portion of the perimeter. LTP broadened the distribution of spine sizes while reducing the presence and proximity of perisynaptic astroglia near the axon-spine interface of large spines. In contrast, cLTD transiently reduced the length of the axon-spine interface perimeter without substantially altering astroglial apposition. The postsynaptic density was discovered to be displaced from the center of the axon-spine interface, with this offset increasing during LTP and decreasing during cLTD. Astroglial access to the postsynaptic density was diminished during LTP and enhanced during cLTD, in parallel with changes in spine size. Thus, access of perisynaptic astroglia to synapses is dynamically modulated during LTP and cLTD alongside synaptic remodeling.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144976899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strengthening Medial Olivocochlear Feedback Reduces the Developmental Impact of Early Noise Exposure.","authors":"Valeria C Castagna, Luis E Boero, Mariano N Di Guilmi, Camila Catalano Di Meo, Jimena A Ballestero, Paul A Fuchs, Amanda M Lauer, Ana Belén Elgoyhen, Maria Eugenia Gomez-Casati","doi":"10.1523/JNEUROSCI.0805-25.2025","DOIUrl":"10.1523/JNEUROSCI.0805-25.2025","url":null,"abstract":"<p><p>The early onset of peripheral deafness significantly alters the proper development of the auditory system. Likewise, exposure to loud noise during early development produces a similar disruptive effect. Before hearing onset in altricial mammals, cochlear inner hair cells (IHCs) exhibit spontaneous electrical activity that drives auditory circuit development. This activity is modulated by medial olivocochlear (MOC) efferent feedback through α9α10 nicotinic cholinergic receptors in IHCs. In adults, these receptors are restricted to outer hair cells, where they mediate MOC feedback to regulate cochlear amplification. Although the MOC system's protective role to prevent noise-induced hearing loss in adulthood is well established, its influence during early developmental stages-especially in response to exposure to loud noise-remains largely unexplored. In this study, we investigated the role of MOC feedback during early postnatal development using α9 knock-out (KO) and α9 knock-in (KI) mice of either sex, which respectively lack or exhibit enhanced cholinergic activity. Our findings reveal that both increased and absent olivocochlear activity result in altered auditory sensitivity at the onset of hearing, along with long-range alterations in the number and morphology of ribbon synapses. Early noise exposure caused lasting auditory damage in both wild-type and α9KO mice, with deficits persisting into adulthood. In contrast, α9KI mice were protected from noise-induced damage, with no long-term effects on auditory function. These results highlight the increased susceptibility of the auditory system during early postnatal development. Moreover, they indicate that an enhanced MOC feedback shields the auditory system from noise damage during this period.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12419220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144884192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}