Journal of Neuroscience最新文献

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Large-Scale Color Biases in the Retinotopic Functional Architecture Are Region Specific and Shared across Human Brains. 视网膜功能结构中的大规模颜色偏差是区域特异性的,并且在人类大脑中是共享的。
IF 4 2区 医学
Journal of Neuroscience Pub Date : 2025-10-15 DOI: 10.1523/JNEUROSCI.2717-20.2025
Michael M Bannert, Andreas Bartels
{"title":"Large-Scale Color Biases in the Retinotopic Functional Architecture Are Region Specific and Shared across Human Brains.","authors":"Michael M Bannert, Andreas Bartels","doi":"10.1523/JNEUROSCI.2717-20.2025","DOIUrl":"10.1523/JNEUROSCI.2717-20.2025","url":null,"abstract":"<p><p>Despite the functional specialization in visual cortex, there is growing evidence that the processing of chromatic and spatial visual features is intertwined. While past studies focused on visual field biases in retina and behavior, large-scale dependencies between coding of color and retinotopic space are largely unexplored in the cortex. Using a sample of male and female volunteers, we asked whether spatial color biases are shared across different human observers and whether they are idiosyncratic for distinct areas. We tested this by predicting the color a person was seeing using a linear classifier that has never been trained on chromatic responses from that same brain, solely by taking into account: (1) the chromatic responses in other individuals' brains and (2) commonalities between the spatial coding in brains used for training and the test brain. We were able to predict the color (and luminance) of stimuli seen by an observer based on other subjects' activity patterns in areas V1-V3, hV4, and LO1. In addition, we found that different colors elicited systematic, large-scale retinotopic biases that were idiosyncratic for distinct areas and common across brains. The area-specific spatial color codes and their conservation across individuals suggest functional or evolutionary organization pressures that remain to be elucidated.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024646","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}
引用次数: 0
Trigeminal motor nucleus regulates microstructure of feeding behavior without affecting total food intake. 三叉神经运动核在不影响总摄食量的情况下调控摄食行为的微观结构。
IF 5.3 2区 医学
Journal of Neuroscience Pub Date : 2025-10-15 DOI: 10.1523/jneurosci.0337-24.2025
Alison Maun Yeng Kok,Yi-Fei Li,Hua Huang,Nan Wang,Yufei Gao,Yu Fu
{"title":"Trigeminal motor nucleus regulates microstructure of feeding behavior without affecting total food intake.","authors":"Alison Maun Yeng Kok,Yi-Fei Li,Hua Huang,Nan Wang,Yufei Gao,Yu Fu","doi":"10.1523/jneurosci.0337-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.0337-24.2025","url":null,"abstract":"Feeding is critical for animal survival and is tightly regulated by designated neural circuits. Several brain regions have been implicated in feeding regulation, including hypothalamus, amygdala, parabrachial nucleus and others. However, how these feeding regulation neurons communicate with the executors of feeding behavior, the trigeminal motor (MoV) neurons that directly control mastication muscles, is unclear. Despite its clear involvement in feeding, MoV is rarely considered as a part of the feeding neural network in literature reviews, indicating an incomplete conceptual framework of feeding regulation. Here, by using Isl1 and ChAT as neuronal markers, we genetically targeted MoV neurons to reveal its connections with other brain regions and investigated their function in feeding in mice of either sex. Notably, we identified direct connection of MoV neurons with forebrain regions including amygdala and BNST, while hypothalamic feeding regulation neurons do not represent as a major direct regulator of MoV neurons. Functionally, although complete silencing of MoV neurons renders the mice incapable of eating, acute inhibition or activation of MoV neurons only changed microstructure of feeding behavior without influencing total food intake, suggesting that MoV neurons mainly function as the executor of feeding but are not involved in appetite regulation. Moreover, activating the GABAergic input neurons of MoV neurons generated similar effect as activating the MoV neurons, because MoV neurons are depolarised by GABA transmission. Together, we established the role of MoV neurons in feeding regulation and advanced the understanding of hindbrain feeding regulation network.Significance Statement Despite the extensive research of hypothalamic feeding regulation neural circuits, the nucleus that controls chewing, trigeminal motor nucleus (MoV), has rarely been considered in literature reviews as part of the feeding circuits, representing a major gap of knowledge in feeding regulation. In this manuscript, we mapped the inputs of MoV neurons using rabies virus method and revealed surprising direct connections with forebrain regions including amygdala. We also examined the functional impact of manipulating MoV neurons, or MoV-projecting CeA neurons, in feeding behavior and confirmed that MoV neurons only fine-tune the microstructure of feeding behavior without influencing total food consumption, suggesting that appetite is controlled by upstream feeding regulation neurons in hypothalamus or other brain regions.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"1 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145296128","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}
引用次数: 0
Intrinsic dendritic integration features of prefrontal layer 5 pyramidal cell subclasses. 前额叶第5层锥体细胞亚类的内在树突整合特征。
IF 5.3 2区 医学
Journal of Neuroscience Pub Date : 2025-10-15 DOI: 10.1523/jneurosci.1080-25.2025
Selin Schamiloglu,Rebecca L Clarkson,Natalia S Stone,Alayna T Liptak,Kevin J Bender
{"title":"Intrinsic dendritic integration features of prefrontal layer 5 pyramidal cell subclasses.","authors":"Selin Schamiloglu,Rebecca L Clarkson,Natalia S Stone,Alayna T Liptak,Kevin J Bender","doi":"10.1523/jneurosci.1080-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.1080-25.2025","url":null,"abstract":"Prefrontal cortex (PFC) is an associative center in the brain and integrates various inputs to support cognition. Layer 5 pyramidal cells are themselves associative centers, as their dendrites span all cortical layers and sample multiple input streams. Backpropagating action potentials (bAPs) are an important mechanism for integrating synaptic inputs arriving at distinct dendritic locations. bAPs originating in the axon initial segment can depolarize the apical dendrite, activate voltage-gated currents that underlie dendritic processing and synaptic plasticity, and influence the integration of synaptic inputs arriving onto apical dendrites. How effectively bAPs depolarize apical dendrites depends on cell type, dendritic morphology, and the dendrite's passive and active properties. Here, we found that in a unique subclass of PFC layer 5 pyramidal cell defined by D3 dopamine receptor (D3R) expression, dendritic calcium responses to bAP stimuli were far greater for a burst of APs than expected from a linear sum of single AP-evoked events in mice of either sex. D3R-expressing neurons electrophysiologically resemble intratelencephalic, D1R-expressing pyramidal neurons but morphologically resemble pyramidal tract, D2R-expressing pyramidal neurons. In both D1R- and D2R-expressing cells, burst-evoked dendritic calcium events largely reflected a linear sum of individual AP responses. In D1R neurons, this was partially due to large conductance calcium-activated potassium (BK) channels, while in D2R neurons, both BK and hyperpolarization-activated cyclic nucleotide-gated channels contributed. These data demonstrate that the intrinsic dendritic excitability of PFC layer 5 pyramidal cells widely differs and suggest that nonlinear dendritic excitability in D3R-expressing neurons uniquely positions these cells within PFC circuits.Significance Statement Layer 5 pyramidal cells associate inputs from diverse information streams to shape behavior. Backpropagating action potentials (bAPs) enable the integration of synaptic inputs that arrive coincidentally on the basal and apical dendrites, but the extent to which bAPs depolarize the apical dendrites can vary across cell types and dendritic morphologies. In prefrontal cortex, layer 5 pyramidal cells can be distinguished based on expression of the D1, D2, or D3 dopamine receptor expression. Here, we examined intrinsic dendritic excitability across D1R, D2R and D3R-expressing neurons and found that bAP-associated dendritic calcium transients vary considerably across these three intermingled neuronal subtypes, suggesting that these pyramidal cell classes have unique roles in prefrontal cortex processing.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"1 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145296129","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}
引用次数: 0
Hippocampal ripples during offline periods predict human motor sequence learning. 离线时期的海马体波纹预测人类运动序列学习。
IF 4 2区 医学
Journal of Neuroscience Pub Date : 2025-10-14 DOI: 10.1523/JNEUROSCI.1502-25.2025
Pin-Chun Chen, Jenny Stritzelberger, Katrin Walther, Hajo Hamer, Bernhard P Staresina
{"title":"Hippocampal ripples during offline periods predict human motor sequence learning.","authors":"Pin-Chun Chen, Jenny Stritzelberger, Katrin Walther, Hajo Hamer, Bernhard P Staresina","doi":"10.1523/JNEUROSCI.1502-25.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1502-25.2025","url":null,"abstract":"<p><p>High-frequency bursts in the hippocampus, known as ripples (80-120 Hz in humans), have been shown to support episodic memory processes. However, converging recent evidence in rodent models and human neuroimaging suggests that the hippocampus may be involved in a wider range of memory domains, including motor sequence learning (MSL). Nevertheless, no direct link between hippocampal ripples and MSL has been established yet. Here, we recorded intracranial electroencephalography (iEEG) from the hippocampus in 20 epilepsy patients (11 males and 9 females) during an MSL task in which participants showed steady improvement across nine 30-second <i>typing</i> blocks interspersed with 30-second <i>rest</i> ('offline') periods. We first demonstrated that ripple rates strongly increased during <i>rest</i> relative to <i>typing</i> blocks. Importantly, ripple rates during rest periods tracked behavioural improvements, both across learning blocks and across participants. These findings suggest that hippocampal ripples during rest periods play a role in facilitating motor sequence learning.<b>Significance Statement</b> This study provides the first direct evidence that hippocampal ripples, brief high-frequency oscillations previously linked to episodic memory, also play a role in human motor sequence learning. By recording intracranial EEG from epilepsy patients during a motor learning task, we found that ripple rates increased during rest periods between typing blocks and closely tracked behavioural improvements in performance. These findings suggest that hippocampal ripples during offline periods may facilitate consolidation of newly acquired motor skills, extending the functional significance of ripples beyond episodic memory.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145294267","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}
引用次数: 0
Selective attention shapes neural representations of complex auditory scenes: The Roles of Object Identity and Scene Composition. 选择性注意塑造复杂听觉场景的神经表征:对象识别和场景构成的作用。
IF 5.3 2区 医学
Journal of Neuroscience Pub Date : 2025-10-14 DOI: 10.1523/jneurosci.0506-25.2025
Patrik Wikman,Ilkka Muukkonen,Jaakko Kauramäki,Ville Laaksonen,Onnipekka Varis,Christopher Petkov,Josef Rauschecker
{"title":"Selective attention shapes neural representations of complex auditory scenes: The Roles of Object Identity and Scene Composition.","authors":"Patrik Wikman,Ilkka Muukkonen,Jaakko Kauramäki,Ville Laaksonen,Onnipekka Varis,Christopher Petkov,Josef Rauschecker","doi":"10.1523/jneurosci.0506-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.0506-25.2025","url":null,"abstract":"Everyday auditory scenes contain overlapping sound objects, requiring attention to isolate relevant objects from irrelevant background objects. This study examined how selective attention shapes neural representations of complex sound scenes in the auditory cortex (AC). Using functional magnetic resonance imaging, we recorded brain activity from participants (12 males, 8 females) as they attended to a designated object in scenes comprising three overlapping sounds. Scenes were constructed in two manners: one where each object belonged to a different category (speech, animal, instrument) and another where all objects were from the same category. Attending to speech enhanced activations in lateral AC subfields, while attention to animal and instrument sounds preferentially modulated medial AC subfields, supporting models where attention modulates feature-selective neural gain in AC. Remarkably, however, spatial pattern analysis revealed that the attended object dominated the AC activation patterns of the entire scene in a manner depending on both object type and scene composition: When scene objects belonged to different categories, attention effects were dominated by category-level processing. In contrast, when all scene objects shared the same category, dominance shifted to exemplar level processing in fields processing acoustic features. Thus, attention seems to dynamically prioritize the features offering maximal contrast within a given context, emphasizing object-specific patterns in feature-similar scenes and category-level patterns in feature-diverse scenes. Our results support models where top-down signals not only modulate gain but also affect scene decomposition and analysis - influencing stream segregation and gating of higher-level processing in a contextual manner, adapting to specific auditory environments.Significance statement Selective attention is essential for filtering behaviorally relevant sounds from complex auditory environments, yet the underlying neural mechanisms remain obscure. We combined fMRI with spatial activation pattern analysis to determine how the auditory cortex attentionally filters different types of sounds (speech, animal, instrument) in complex scenes composed of three sounds, either from different or the same categories. Attentional filtering depended both on the object type and on scene composition. Our data suggest that in the auditory cortex attentional filtering operates on category-level features in multi-category scenes, while exemplar-level features prevail in same-category scenes. Thus, top-down attention not only modulates neural gain but also affects scene decomposition and gating of higher-level processing in a contextual manner, adapting to specific auditory environments.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"23 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145288480","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}
引用次数: 0
Superior colliculus projections drive dopamine neuron activity and movement but not value. 上丘投射驱动多巴胺神经元的活动和运动,但不驱动价值。
IF 4 2区 医学
Journal of Neuroscience Pub Date : 2025-10-14 DOI: 10.1523/JNEUROSCI.0291-25.2025
Carli L Poisson, Izzabella K Green, Gretchen M Stemmler, Julianna Prohofsky, Amy R Wolff, Cassandra Herubin, Madelyn Blake, Benjamin T Saunders
{"title":"Superior colliculus projections drive dopamine neuron activity and movement but not value.","authors":"Carli L Poisson, Izzabella K Green, Gretchen M Stemmler, Julianna Prohofsky, Amy R Wolff, Cassandra Herubin, Madelyn Blake, Benjamin T Saunders","doi":"10.1523/JNEUROSCI.0291-25.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.0291-25.2025","url":null,"abstract":"<p><p>To navigate dynamic environments, animals must rapidly integrate sensory information and respond appropriately to gather rewards and avoid threats. It is well established that dopamine (DA) neurons in the ventral tegmental area (VTA) and substantia nigra (SNc) are key for creating associations between environmental stimuli (i.e., cues) and the outcomes they predict. Critically, it remains unclear how sensory information is integrated into dopamine pathways. The superior colliculus (SC) receives direct visual input and is positioned as a relay for dopamine neuron augmentation. We characterized the anatomy and functional impact of SC projections to the VTA/SNc in male and female rats. First, we show that neurons in the deep layers of SC synapse densely throughout the ventral midbrain, interfacing with projections to the striatum and ventral pallidum, and these SC projections excite dopamine and GABA neurons in the VTA/SNc in vivo. Despite this, cues predicting SC→VTA/SNc neuron activation did not reliably evoke behavior in an optogenetic Pavlovian conditioning paradigm, and activation of SC→VTA/SNc neurons did not support primary reinforcement or produce place preference/avoidance. Instead, we find that stimulation of SC→VTA/SNc neurons evokes head turning. Focusing optogenetic activation solely onto dopamine neurons that receive input from the SC was sufficient to invigorate turning, but not reinforcement. Turning intensity increased with repeated stimulations, suggesting that this circuit may underlie sensorimotor learning for exploration and attentional switching. Together, our results show that collicular neurons contribute to cue-guided behaviors by controlling pose adjustments through interaction with dopamine neurons that preferentially engage movement instead of reward.<b>Significance Statement</b> In dynamic environments, animals must rapidly integrate sensory information and respond appropriately to survive. Dopamine (DA) neurons are key for creating associations between environmental cues through learning, but it remains unclear how relevant sensory information is integrated into DA pathways to guide this process. The superior colliculus (SC) is positioned for rapid sensory augmentation of dopamine neurons. Using a combination of approaches, we find that SC neurons projecting to the ventral midbrain activate dopamine neurons and drive postural changes without creating conditioned behavior or valence. Our results highlight a brain circuit that is important for guiding movement to redirect attention, via interaction with classic learning systems, and suggest distinct subpopulations of dopamine neurons preferentially engage movement instead of reward.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145294270","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}
引用次数: 0
Complementary yet dissociable influences of medial and lateral orbitofrontal cortex over cue-guided decisions involving reward magnitude and uncertainty. 内侧和外侧眶额皮质对涉及奖励大小和不确定性的线索引导决策的互补但可分离的影响。
IF 5.3 2区 医学
Journal of Neuroscience Pub Date : 2025-10-14 DOI: 10.1523/jneurosci.1989-24.2025
Jackson D Schumacher,Mieke van Holstein,Peiran Zhou,Paula E MacLeod,Vaishali Bagrodia,Stan B Floresco
{"title":"Complementary yet dissociable influences of medial and lateral orbitofrontal cortex over cue-guided decisions involving reward magnitude and uncertainty.","authors":"Jackson D Schumacher,Mieke van Holstein,Peiran Zhou,Paula E MacLeod,Vaishali Bagrodia,Stan B Floresco","doi":"10.1523/jneurosci.1989-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.1989-24.2025","url":null,"abstract":"Converging evidence suggests that orbitofrontal cortex (OFC) subregions subserve distinct roles in decision making across a variety of tasks. Cost/benefit decisions can require an organism to choose between options based on information available in the environment (externally-guided) and knowledge from experience (internally-guided). Studies in humans have implicated both medial and lateral subdivisions of OFC (mOFC, lOFC) in externally and internally guided choice, yet, rodent studies have primarily focused on OFC regulation of internally-guided decisions. To address this gap, we examined how inactivation of these OFC subregions alters cue-guided, probabilistic decision making using a \"Blackjack\" task. Male rats were required to choose between a certain, 1-pellet small reward and larger, 4-pellet reward delivered with varying probability, signalled trail-to-trial with explicit auditory stimuli indicating whether the odds of receiving the larger reward was good (50%) or poor (12.5%). Inactivation of the mOFC or lOFC induced generalized decreases or increases in large/risky choice, respectively, that were associated with opposite effects on loss (but not win) sensitivity and on rats' likelihood of making consecutive choices of the small/certain option. Inactivation of the adjacent anterior agranular insular cortex had no effect. Inactivation of either OFC subregion also disrupted cue-guided reward magnitude discrimination, where tones signals which action delivered a deterministic larger reward, but did not affect a simpler conditional discrimination involving choice between rewarded and unrewarded actions. Together these data highlight complementary yet heterogeneous roles for different OFC regions in using discriminative stimuli to guide action towards higher value targets.Significance Statement The orbitofrontal cortex mediates risk/reward decisions across species. This region can be partitioned into medial and lateral compartments that have distinct connectivity, yet there have been few studies directly comparing their involvement in these types of decisions. Here we show these two orbitofrontal regions play opposing roles in biasing risky choices guided by external stimuli informing about the likelihood of receiving larger, uncertain rewards, while playing complementary roles in using cues to guide action towards larger deterministic rewards. These findings broaden our understanding of how different frontal lobe regions influence these types of decisions and further highlight differences in how these systems are recruited in shaping decision biases guided by external cues vs internal representations of risk/reward contingencies.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"117 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145288406","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}
引用次数: 0
Active zone maturation controls presynaptic output and release mode and is regulated by neuronal activity. 活跃区成熟控制突触前输出和释放模式,并受神经元活动调节。
IF 5.3 2区 医学
Journal of Neuroscience Pub Date : 2025-10-14 DOI: 10.1523/jneurosci.1143-25.2025
Yulia Akbergenova,Jessica Matthias,Sofya Makeyeva,J Troy Littleton
{"title":"Active zone maturation controls presynaptic output and release mode and is regulated by neuronal activity.","authors":"Yulia Akbergenova,Jessica Matthias,Sofya Makeyeva,J Troy Littleton","doi":"10.1523/jneurosci.1143-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.1143-25.2025","url":null,"abstract":"Synapse formation requires the accumulation of cytomatrix proteins and voltage-gated Ca2+ channels (VGCCs) at presynaptic active zones (AZs). At Drosophila melanogaster larval neuromuscular junctions, a sequential process of AZ maturation is observed, with initial incorporation of early scaffolds followed by arrival of late scaffolds and VGCCs. To examine how AZ maturation regulates presynaptic output, serial imaging of AZ formation and function was performed at time-stamped synapses of male larvae expressing glutamate receptors linked to the photoconvertible protein mMaple. Quantal imaging demonstrated older synapses have higher synaptic efficacy and sustain greater release across development, while immature sites lacking VGCC accumulation supported spontaneous fusion. To examine how activity regulates AZ maturation, the effects of cell autonomous disruptions to neurotransmitter release were analyzed. Decreased synaptic transmission reduced AZ seeding and caused hyperaccumulation of material at existing AZs. Generation of an endogenous photoconvertible version of the AZ scaffold protein BRP revealed neuronal silencing decreased the protein's turnover. Although enlarged AZs are also observed in rab3 mutants, activity reduction acted through an independent mechanism that required postsynaptic glutamate receptor-dependent signaling. Endogenous tagging of the Unc13B early AZ scaffold and the Unc13A late AZ scaffold revealed activity reduction decreased seeding of both early and late scaffolds, in contrast to rab3 mutants. Together, these data indicate AZ maturation regulates presynaptic release mode and output strength, with neuronal activity shaping both AZ number and size across development.Significance Statement How presynaptic development regulates neurotransmitter release output and the role of synaptic activity in active zone (AZ) maturation are unclear. Here, we perform birth dating and serial in vivo imaging of AZs over a multi-day period during Drosophila larval development. We find synaptic maturation regulates the strength of synaptic output and the timing of spontaneous versus evoked release. Synaptic activity modulates AZ material accumulation and seeding of new release sites, with disruptions to neurotransmitter release reducing AZ number and driving enhanced AZ material accumulation at fewer release sites.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"102 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145288405","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}
引用次数: 0
Q Neuron-Induced Hypothermia Promotes Functional Recovery and Suppresses Neuroinflammation After Brain Injury. 神经元诱导的低温促进脑损伤后功能恢复和抑制神经炎症。
IF 5.3 2区 医学
Journal of Neuroscience Pub Date : 2025-10-13 DOI: 10.1523/jneurosci.1035-25.2025
Lisa Sakurai,Ryusuke Yoshimoto,Shingo Soya,Takeshi Sakurai
{"title":"Q Neuron-Induced Hypothermia Promotes Functional Recovery and Suppresses Neuroinflammation After Brain Injury.","authors":"Lisa Sakurai,Ryusuke Yoshimoto,Shingo Soya,Takeshi Sakurai","doi":"10.1523/jneurosci.1035-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.1035-25.2025","url":null,"abstract":"Traumatic brain injury (TBI) triggers a cascade of secondary pathologies-such as neuroinflammation and glial activation-that contribute to progressive neuronal loss and hinder functional recovery. While therapeutic hypothermia has shown neuroprotective potential, its clinical application is limited by systemic complications. Recent discoveries have identified hypothalamic Q neurons, whose activation induces a reversible, hibernation-like hypothermic state, termed Q neurons-induced hypothermic/hypometabolic states (QIH), without the need for external cooling. However, whether QIH can mitigate brain injury remains unknown. In this study, we examined the therapeutic effects of QIH following acute brain injury in male mice. Using a dorsal striatal stab injury model, we found that QIH-treated mice displayed significantly improved motor performance and grip strength compared to controls. Histological analyses revealed enhanced neuronal survival in the perilesional striatum, accompanied by markedly reduced astrocytic gliosis and microglial accumulation at the injury site.To investigate the mechanisms underlying these improvements, we employed a medial prefrontal cortex injury model and observed that QIH robustly suppressed astrocytic and microglial activation, as indicated by reduced GFAP and Iba1 expression. Additionally, QIH decreased the number of CD16/32- and CD68-positive microglia and downregulated iNOS expression, suggesting that QIH dampens both oxidative and phagocytic inflammatory responses. Morphometric analysis further revealed a shift toward ramified and rod-shaped microglia; phenotypes associated with neuroprotection. Our findings demonstrate that QIH ameliorates early neuroinflammation, preserves neuronal integrity, and promotes functional recovery following brain injury. These results highlight QIH as a novel and physiologically grounded neuroprotective strategy that may overcome the limitations of conventional hypothermia-based interventions.Significance Statement Traumatic brain injury (TBI) often leads to long-term neurological impairments due to glial activation and neuroinflammation. Although therapeutic hypothermia can reduce secondary damage, its clinical use is limited by systemic side effects. Here, we demonstrate that a hibernation-like state induced by hypothalamic Q neurons-Q neurons-induced hypothermic/hypometabolic states (QIH)-improves motor function, enhances neuronal survival, and suppresses early neuroinflammatory responses in mouse models of brain injury. QIH attenuated astrocytic and microglial activation and promoted the emergence of neuroprotective microglial morphologies. These results suggest that QIH is a promising and physiologically regulated neuroprotective strategy. Unlike traditional hypothermia, QIH avoids external cooling, offering a potentially safer and more practical approach to TBI treatment.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"13 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283792","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}
引用次数: 0
Behavior-relevant periodized neural representation of acoustic but not tactile rhythm in humans. 人类听觉节奏而非触觉节奏的行为相关周期神经表征。
IF 4 2区 医学
Journal of Neuroscience Pub Date : 2025-10-13 DOI: 10.1523/JNEUROSCI.0664-25.2025
Lenoir Cédric, Lenc Tomas, Polak Rainer, Nozaradan Sylvie
{"title":"Behavior-relevant periodized neural representation of acoustic but not tactile rhythm in humans.","authors":"Lenoir Cédric, Lenc Tomas, Polak Rainer, Nozaradan Sylvie","doi":"10.1523/JNEUROSCI.0664-25.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.0664-25.2025","url":null,"abstract":"<p><p>Music makes people move. This human propensity to coordinate movement with musical rhythm requires multiscale temporal integration, allowing fast sensory events composing rhythmic input to be mapped onto slower, behavior-relevant, internal templates such as periodic beats. Relatedly, beat perception has been shown to involve an enhanced representation of the beat periodicities in neural activity. However, the extent to which this ability to move to the beat, and the related <i>periodized</i> neural representation, are shared across the senses beyond audition remains unknown. Here, we addressed this question by recording separately the electroencephalographic responses (EEG) and finger tapping to a rhythm conveyed either through acoustic or tactile inputs in healthy volunteers of either sex. The EEG responses to the acoustic rhythm, spanning a low-frequency range (below 15 Hz), showed enhanced representation of the perceived periodic beat, compatible with behavior. In contrast, the EEG responses to the tactile rhythm, spanning a broader frequency range (up to 25 Hz), did not show significant beat-related periodization, and yielded less stable tapping. Together, these findings suggest a preferential role of low-frequency neural activity in supporting neural representation of the beat. Most importantly, we show that this neural representation, as well as the ability to move to the beat, is not systematically shared across the senses. More generally, these results, highlighting multimodal differences in beat processing, reveal a process of multiscale temporal integration that allows the auditory system to go beyond mere tracking of onset timing and to support higher-level internal representation and motor entrainment to rhythm.<b>Significance statement</b> Integrating fast sensory events composing music into slower temporal units is a cornerstone of beat perception. This study shows that this ability relies critically on low frequency brain activity, below the sensory event rate, in response to acoustic rhythm. Conversely, brain responses elicited by the same tactile rhythm exhibit higher frequency activity corresponding to faithful tracking of the sensory event rate. Critically, the auditory-specific slow fluctuations feature an enhanced representation of the perceived periodic beat, compatible with behavior. This higher-level neural processing of rhythmic input could thus reflect internal representations of the beat that are not shared across senses, highlighting multimodal differences in beat processing. These results pave the way to explore high-level multimodal perception and motor entrainment in humans.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145287583","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}
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