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Synchrony timescales underlie irregular neocortical spiking. 同步时间尺度是不规则新皮质尖峰的基础。
IF 15 1区 医学 Q1 NEUROSCIENCES Pub Date : 2025-12-17 DOI: 10.1016/j.neuron.2025.11.005
Jagruti J Pattadkal, Ronan T O'Shea, David Hansel, Thibaud Taillefumier, Darrin H Brager, Nicholas J Priebe

Cortical neurons are characterized by their variable spiking patterns. Here, we examine the specific hypothesis that cortical synchrony drives spiking variability in vivo. Using dynamic clamps, we demonstrate that intrinsic neuronal properties do not contribute substantially to spiking variability, but rather spiking variability emerges from weakly synchronous network drive. With large-scale electrophysiology, we quantify the degree of synchrony and its timescale in cortical networks in vivo. The timescale of synchrony shifts in a range from 25 to 200 ms, depending on the presence of external sensory input. In particular, when the network moves from spontaneous to driven modes, the synchrony timescales shift from slow to fast, leading to a natural reduction in response variability across cortical areas. Finally, while an individual neuron exhibits reliable responses to physiological drive, different neurons respond in a distinct fashion according to their intrinsic properties, contributing to stable synchrony across the neural network.

皮质神经元的特点是其可变的尖峰模式。在这里,我们研究了皮层同步驱动体内尖峰变异性的特定假设。使用动态钳,我们证明了内在的神经元特性对尖峰可变性没有实质性的贡献,而是来自弱同步网络驱动的尖峰可变性。通过大规模电生理学,我们量化了体内皮质网络的同步程度及其时间尺度。同步的时间尺度在25到200毫秒的范围内变化,这取决于外部感官输入的存在。特别是,当网络从自发模式转变为驱动模式时,同步时间尺度从慢到快,导致皮层区域的反应可变性自然减少。最后,虽然单个神经元对生理驱动表现出可靠的反应,但不同的神经元根据其内在特性以不同的方式做出反应,从而促进整个神经网络的稳定同步。
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引用次数: 0
Regionally mapped astrocytic responses to cortical and white matter stroke show differential roles in astrocyte-induced vascular remodeling. 区域星形胶质细胞对皮层和白质中风的反应显示了星形胶质细胞诱导的血管重构的不同作用。
IF 15 1区 医学 Q1 NEUROSCIENCES Pub Date : 2025-12-17 Epub Date: 2025-10-10 DOI: 10.1016/j.neuron.2025.09.023
Amy J Gleichman, Riki Kawaguchi, Elle M Rathbun, Michael V Sofroniew, S Thomas Carmichael

Stroke is a major cause of disability. Astrocytes respond to stroke in a gradated manner, but details of that response and its consequences for tissue repair are poorly understood, particularly across brain regions and stroke subtypes. We identified phenotypically and morphologically distinct zones of reactive astrocytes in mouse models of cortical and white matter stroke. Zone-specific transcriptomic analyses revealed that cortical, but not white matter, astrocytes upregulated transcriptional programs promoting the formation of new blood vessels, a key repair mechanism. Viral gain- and loss-of-function strategies showed that astrocytic Lamc1, in particular, is an endogenous mechanism by which cortical, but not white matter, astrocytes drive remodeling of larger-caliber brain microvessels. Exogenous induction of Lamc1 in white matter astrocytes improved vessel remodeling and repair and triggered differential T cell infiltration post stroke. Astrocyte subpopulations show region-specific responses to ischemia that can be leveraged to promote repair, including astrocyte-induced vascular remodeling.

中风是致残的主要原因。星形胶质细胞以一种分级的方式对中风作出反应,但这种反应的细节及其对组织修复的影响尚不清楚,特别是在大脑区域和中风亚型之间。我们在小鼠脑皮层和脑白质中风模型中发现了反应性星形胶质细胞在表型和形态学上的不同区域。区域特异性转录组学分析显示,皮质而非白质星形胶质细胞上调了促进新血管形成的转录程序,这是一种关键的修复机制。病毒的功能获得和功能丧失策略表明,星形细胞Lamc1是一种内源性机制,通过这种机制,皮质而非白质星形细胞驱动大口径脑微血管的重塑。外源性Lamc1诱导白质星形胶质细胞改善血管重塑和修复,并引发脑卒中后差异T细胞浸润。星形胶质细胞亚群对缺血表现出区域特异性反应,可以促进修复,包括星形胶质细胞诱导的血管重塑。
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引用次数: 0
Neurovascular dynamics in the spinal cord from development to pathophysiology. 从发育到病理生理的脊髓神经血管动力学。
IF 15 1区 医学 Q1 NEUROSCIENCES Pub Date : 2025-12-17 Epub Date: 2025-10-14 DOI: 10.1016/j.neuron.2025.09.017
Carmen Ruiz de Almodovar, Sebastian Dupraz, Dario Bonanomi

The vasculature is increasingly recognized as an active regulator of homeostasis and repair, beyond conventional roles in nutrient delivery. In the central nervous system, vascular cells adopt region-specific traits tailored to the distinct demands of the brain, retina, and spinal cord. Despite long-standing interest in the spinal cord as a model for neural development and injury, its vascular organization and properties remain understudied. The assumption that spinal cord and brain neurovascular systems are built and function in the same way has limited progress. Here, we challenge this view by examining specific properties underlying spinal cord vascular development, physiology, and pathology. We highlight unique angioarchitecture and homeostatic mechanisms, and discuss how neurovascular disruption contributes to spinal disorders and regenerative failure after injury. Identifying critical knowledge gaps, we aim to stimulate new research in spinal cord neurovascular biology, redefining its importance for health and disease.

血管系统越来越被认为是一个主动调节和修复,超越了传统的作用,在营养输送。在中枢神经系统中,血管细胞根据大脑、视网膜和脊髓的不同需求,具有特定区域的特征。尽管长期以来人们对脊髓作为神经发育和损伤的模型感兴趣,但其血管组织和特性仍未得到充分研究。认为脊髓和脑神经血管系统的构造和功能相同的假设进展有限。在这里,我们通过检查脊髓血管发育、生理和病理的特定特性来挑战这一观点。我们强调独特的血管结构和内稳态机制,并讨论神经血管破坏如何导致损伤后脊柱疾病和再生衰竭。确定关键的知识差距,我们的目标是刺激脊髓神经血管生物学的新研究,重新定义其对健康和疾病的重要性。
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引用次数: 0
Restoration of temporal separability between beta and movement ensemble co-firing with motor recovery. 与运动恢复共燃的β和运动集合的时间可分离性的恢复。
IF 15 1区 医学 Q1 NEUROSCIENCES Pub Date : 2025-12-17 Epub Date: 2025-10-08 DOI: 10.1016/j.neuron.2025.09.013
Hoseok Choi, Jaekyung Kim, Preeya Khanna, Sandon Griffin, Lisa Novik, Robert J Morecraft, John H Morrison, Karunesh Ganguly

Stroke disrupts movement control by damaging descending motor pathways, yet the cortical dynamics underlying recovery remain poorly defined. Using a non-human primate model of primary motor cortex injury with impaired reach-to-grasp control, we examined how dorsal premotor cortex (PMd) activity supports recovery. Specifically, we studied the interaction between beta activity (12-30 Hz), often linked to "idle" states, and execution-related ensemble co-firing quantified with dimensionality reduction. Stroke impaired the temporal separability between beta bursts and movement-related co-firing, leading to slower reaction times and reduced performance. Recovery was associated with increased separability, and during grasping, beta activity progressively declined with recovery. These results indicate that reliable transitions between high-beta idle and high co-firing execution states are important for movement control, whereas pathological beta intrusions during execution degrade performance. Importantly, low-frequency alternating current stimulation (ACS) via a ringtrode interface enhanced temporal separability and improved reach-to-grasp performance, highlighting a potential therapeutic strategy.

中风通过破坏下行运动通路来破坏运动控制,然而大脑皮层的动态恢复仍不明确。利用非人类灵长类动物的原发性运动皮质损伤模型,我们研究了背侧运动前皮质(PMd)活动如何支持恢复。具体来说,我们研究了通常与“空闲”状态相关的β活动(12-30 Hz)与执行相关的集成共燃烧之间的相互作用,并通过降维量化。中风损害了β爆发和运动相关的共燃之间的时间分离性,导致反应时间变慢和表现下降。恢复与可分离性增加有关,在抓握期间,β活性随着恢复逐渐下降。这些结果表明,在高β -空闲和高共燃执行状态之间的可靠转换对运动控制很重要,而在执行过程中病理β -侵入会降低性能。重要的是,通过环极界面的低频交流电刺激(ACS)增强了时间可分离性,改善了手握性能,凸显了一种潜在的治疗策略。
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引用次数: 0
PV interneurons gate sex-specific winner effects. PV中间神经元控制性别特异性赢家效应。
IF 15 1区 医学 Q1 NEUROSCIENCES Pub Date : 2025-12-17 DOI: 10.1016/j.neuron.2025.11.025
Xinli Song, Yu Chen, Kun Li

Winner effects, where past victories enhance success, shape competition. In this issue of Neuron, Zheng et al.1 show that female mice form hierarchies with weaker winner effects because prefrontal interneurons limit thalamic-prefrontal synaptic strengthening, revealing a framework for sex differences in social dominance.

赢家效应,即过去的胜利增强了成功,塑造了竞争。在本期《神经元》杂志上,Zheng等人1表明,由于前额叶中间神经元限制了丘脑-前额叶突触的强化,雌性小鼠形成了具有较弱赢家效应的等级结构,揭示了社会支配性性别差异的框架。
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引用次数: 0
PsychENCODE at 10: From genomic maps to mechanistic insights in mental illness. 10点精神编码:从基因组图谱到精神疾病的机制洞察。
IF 15 1区 医学 Q1 NEUROSCIENCES Pub Date : 2025-12-17 DOI: 10.1016/j.neuron.2025.11.027
Panos Roussos, Flora M Vaccarino, Zhiping Weng, Nenad Sestan, Mark Gerstein, Daniel H Geschwind

Over the past decade, the PsychENCODE Consortium has transformed psychiatric genomics-from static maps of genetic risk to dynamic, cell-resolved models of the human brain-linking DNA sequence to neural circuitry and behavior and laying the foundation for precision approaches to mental illness.

在过去的十年里,PsychENCODE联盟已经将精神病学基因组学从静态的遗传风险图谱转变为动态的、细胞解析的人脑模型,将DNA序列与神经回路和行为联系起来,为精确治疗精神疾病奠定了基础。
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引用次数: 0
Distinct representations of economic variables across regions and projections of the frontal cortex. 经济变量跨区域和额叶皮质投影的不同表现。
IF 15 1区 医学 Q1 NEUROSCIENCES Pub Date : 2025-12-17 Epub Date: 2025-10-16 DOI: 10.1016/j.neuron.2025.09.027
Antara Majumdar, Caitlin Ashcroft, Matthias Fritsche, Sandra Tan, Peter Zatka-Haas, Orsolya Folsz, Niamh Walker, Leah Mistry, Anita M Rominto, Marko Tvrdic, Zoltán Molnár, Huriye Atilgan, Adam M Packer, Simon J B Butt, Armin Lak

Economic decision-making requires evaluating information about available options, such as their expected value and economic risk. Previous studies have shown that frontal cortical neurons encode these variables, but how this encoding is structured across different frontal regions and projection pathways remains unclear. We developed a decision-making task for head-fixed mice in which we varied the expected value and risk associated with reward-predicting stimuli. Using large-scale electrophysiology, two-photon imaging, and projection-specific optotagging, we identified distinct spatial gradients for these variables, with stronger expected value coding in dorsal frontal regions and stronger risk coding in medial regions. We then demonstrated that this encoding further depends on the neuronal projections: frontal neurons projecting to the dorsomedial striatum and claustrum differentially encoded economic variables. Our findings illustrate that frontal cortical representation of economic variables is jointly determined by spatial organization and downstream connectivity of neurons, revealing a structured, multi-scale code for economic variables.

经济决策需要评估有关可用选项的信息,例如它们的预期价值和经济风险。先前的研究表明,额叶皮质神经元对这些变量进行编码,但这种编码是如何在不同的额叶区域和投射路径上进行构建的,目前尚不清楚。我们为头部固定的小鼠开发了一个决策任务,在这个任务中,我们改变了与奖励预测刺激相关的期望值和风险。通过大规模电生理学、双光子成像和投影特异性光标记,我们确定了这些变量的不同空间梯度,在额背区域有更强的期望值编码,在内侧区域有更强的风险编码。然后,我们证明了这种编码进一步依赖于神经元的投射:额叶神经元投射到背内侧纹状体和屏状体的经济变量编码不同。研究结果表明,额叶皮层对经济变量的表征是由神经元的空间组织和下游连通性共同决定的,揭示了经济变量的结构化、多尺度编码。
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引用次数: 0
Linguistic coupling between neural systems for speech production and comprehension during real-time dyadic conversations. 实时二元对话中语音产生和理解的神经系统之间的语言耦合。
IF 15 1区 医学 Q1 NEUROSCIENCES Pub Date : 2025-12-17 DOI: 10.1016/j.neuron.2025.11.004
Zaid Zada, Samuel A Nastase, Sebastian Speer, Laetitia Mwilambwe-Tshilobo, Lily Tsoi, Shannon M Burns, Emily Falk, Uri Hasson, Diana I Tamir

The core use of human language is to send complex ideas from one mind to another. In everyday conversations, comprehension and production are intertwined, as speakers and listeners alternate roles. Nonetheless, the neural systems underlying these faculties are typically studied in isolation, using paradigms that cannot capture interactive communication. Here, we used fMRI hyperscanning to simultaneously record dyads engaged in real-time conversations. We used language model embeddings to quantify the degree to which production and comprehension systems rely on shared neural representations, both within and across brains. We found that both processes key into overlapping neural systems, with similar neural tuning for both processes, spanning the cortical language network. Speaker-listener coupling extended beyond the language network into areas associated with social cognition. Our results suggest that the neural systems for speech comprehension and production align with common linguistic features encoded in a broad cortical network for language and communication.

人类语言的核心用途是将复杂的思想从一个人的头脑传递给另一个人。在日常对话中,理解和表达是交织在一起的,因为说话者和听者的角色是交替的。然而,这些功能背后的神经系统通常是孤立地研究的,使用的范式无法捕捉互动交流。在这里,我们使用功能磁共振成像(fMRI)超扫描来同时记录参与实时对话的二人组。我们使用语言模型嵌入来量化生产和理解系统在多大程度上依赖于大脑内部和跨大脑的共享神经表征。我们发现这两个过程都是重叠神经系统的关键,两个过程都有类似的神经调节,跨越皮层语言网络。说者-听者的耦合从语言网络扩展到与社会认知相关的领域。我们的研究结果表明,语音理解和产生的神经系统与语言和交流的广泛皮质网络中编码的共同语言特征一致。
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引用次数: 0
Lcn2 from neutrophil extracellular traps induces astrogliosis and post-stroke emotional disorders. 来自中性粒细胞胞外陷阱的Lcn2诱导星形胶质细胞增生和中风后情绪障碍。
IF 15 1区 医学 Q1 NEUROSCIENCES Pub Date : 2025-12-17 Epub Date: 2025-10-10 DOI: 10.1016/j.neuron.2025.09.018
Yuan Liu, Wei Lin, Zhongfei Bai, Yuting Ge, Yuanjie Xiao, Feifei Zhu, Jing Zhang, Bingying Wang, Qiyang Li, Li Gao, Yan Li, Chunlei Shan, Jun Nagai, Yiwen Wu, Tian-Le Xu, Zhengrun Gao

Patients with an ischemic stroke are often predisposed to emotional disorders. However, the mechanisms underlying post-stroke emotional disorders (PSEDs) remain unclear. Recent research highlights the role of neuroinflammation, driven primarily by infiltration of circulating immune cells within the brain parenchyma and accompanied by blood-brain barrier (BBB) disruption, in secondary emotional disorders. Combining human cohort and animal model data, we identified serum neutrophil extracellular traps (NETs) as significant contributors to PSEDs. Conditional knockout strategies and -omics analyses convergently identified central NETs as the specific modulator of PSEDs. We further elucidated that astrogliosis is catalyzed by lipocalin 2 (Lcn2) released from NETs, which constituted the core mechanism underlying PSEDs. Additionally, we provided proof-of-concept evidence that transcranial direct current stimulation (tDCS) can suppress Lcn2 release and alleviate PSEDs. Collectively, these findings delineated a distinct peripheral-central neuroimmune interaction pattern following BBB damage and highlighted the potential of non-invasive stimulation in effectively reshaping the neuroimmune environment.

缺血性中风患者往往易患情绪障碍。然而,中风后情绪障碍的机制尚不清楚。最近的研究强调了神经炎症在继发性情绪障碍中的作用,神经炎症主要是由脑实质内循环免疫细胞的浸润所驱动,并伴有血脑屏障(BBB)的破坏。结合人类队列和动物模型数据,我们确定血清中性粒细胞胞外陷阱(NETs)是psd的重要贡献者。条件敲除策略和组学分析将中心NETs识别为psd的特定调节剂。我们进一步阐明了星形胶质细胞形成是由NETs释放的脂质钙素2 (lipocalin 2, Lcn2)催化的,这是psd的核心机制。此外,我们提供了经颅直流电刺激(tDCS)可以抑制Lcn2释放并减轻psd的概念验证证据。总的来说,这些发现描绘了血脑屏障损伤后明显的外周-中枢神经免疫相互作用模式,并强调了非侵入性刺激在有效重塑神经免疫环境方面的潜力。
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引用次数: 0
Hippocampal ripple diversity organizes neuronal reactivation dynamics in the offline brain. 海马体纹波多样性组织离线大脑中的神经元再激活动力学。
IF 15 1区 医学 Q1 NEUROSCIENCES Pub Date : 2025-12-17 Epub Date: 2025-10-02 DOI: 10.1016/j.neuron.2025.09.012
Manfredi Castelli, Vítor Lopes-Dos-Santos, Giuseppe P Gava, Renaud Lambiotte, David Dupret

Hippocampal ripples are highly synchronized neuronal population patterns reactivating past waking experiences in the offline brain. Whether the level, structure, and content of ripple-nested activity are consistent across consecutive events or are tuned in each event remains unclear. By profiling individual ripples using laminar currents in the mouse hippocampus during sleep/rest, we identified ripples in stratum pyramidale that feature current sinks in stratum radiatum (Radsink) versus stratum lacunosum-moleculare (LMsink). These two ripple profiles recruit neurons differently. Radsink ripples integrate recent motifs of waking coactivity, combining superficial and deep CA1 principal cells into denser, higher-dimensional patterns that undergo hour-long stable reactivation. By contrast, LMsink ripples contain core motifs of prior coactivity, engaging deep cells in sparser, lower-dimensional patterns that undergo a reactivation drift to gradually update their pre-existing content for recent wakefulness. We propose that ripple-by-ripple diversity supports parallel reactivation channels for integrating recent wakefulness while updating prior representations.

海马体波纹是高度同步的神经元群模式,在离线的大脑中重新激活过去清醒时的经历。波纹嵌套活动的级别、结构和内容是否在连续事件中是一致的,还是在每个事件中都进行了调优,目前还不清楚。通过使用睡眠/休息期间小鼠海马体中的层流分析单个波纹,我们确定了金字塔层中的波纹,其特征是辐射层(Radsink)和缝隙层-分子层(LMsink)的电流汇。这两种纹波曲线募集神经元的方式不同。Radsink波纹整合了最近清醒时的协同活动,将表层和深层CA1主细胞结合成更密集、更高维度的模式,经历长达一小时的稳定再激活。相比之下,LMsink波纹包含先前协同活动的核心主题,使深层细胞以更稀疏、更低维度的模式参与其中,这些细胞经历再激活漂移,逐渐更新其先前存在的内容,以适应最近的清醒状态。我们提出逐波多样性支持并行再激活通道,以整合最近的觉醒,同时更新先前的表征。
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引用次数: 0
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Neuron
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