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Functional properties of corticothalamic circuits targeting paraventricular thalamic neurons. 以丘脑室旁神经元为目标的皮质-丘脑回路的功能特性
IF 14.7 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-11-02 DOI: 10.1016/j.neuron.2024.10.010
Guillermo Aquino-Miranda, Dounya Jalloul, Xu O Zhang, Sa Li, Gilbert J Kirouac, Michael Beierlein, Fabricio H Do Monte

Corticothalamic projections to sensorimotor thalamic nuclei show modest firing rates and serve to modulate the activity of thalamic relay neurons. By contrast, here we find that high-order corticothalamic projections from the prelimbic (PL) cortex to the anterior paraventricular thalamic nucleus (aPVT) maintain high-frequency activity and evoke strong synaptic excitation of aPVT neurons in rats. In a significant fraction of aPVT cells, such high-frequency excitation of PL-aPVT projections leads to a rapid decay of action potential amplitudes, followed by a depolarization block (DB) that strongly limits aPVT maximum firing rates, thereby regulating both defensive and appetitive behaviors in a frequency-dependent manner. Strong inhibitory inputs from the anteroventral portion of the thalamic reticular nucleus (avTRN) inhibit the firing rate of aPVT neurons during periods of high-spike fidelity but restore it during prominent DB, suggesting that avTRN activity can modulate the effects of PL inputs on aPVT firing rates to ultimately control motivated behaviors.

皮质-丘脑向丘脑感觉运动核的投射显示出适度的发射率,并起到调节丘脑中继神经元活动的作用。相比之下,我们在这里发现,从边缘前皮层(PL)到丘脑前室旁核(aPVT)的高阶皮质-丘脑投射保持着高频率的活动,并唤起大鼠 aPVT 神经元的强烈突触兴奋。在很大一部分 aPVT 细胞中,PL-aPVT 投射的这种高频兴奋导致动作电位振幅快速衰减,随后出现去极化阻滞(DB),强烈限制了 aPVT 的最大发射率,从而以频率依赖性方式调节防御和食欲行为。丘脑网状核(avTRN)前腹部的强抑制性输入在高棘波保真度期间抑制了 aPVT 神经元的发射率,但在突出的 DB 期间恢复了发射率,这表明 avTRN 的活动可以调节 PL 输入对 aPVT 发射率的影响,从而最终控制动机行为。
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引用次数: 0
Defining cardioception: Heart-brain crosstalk. 定义心感:心脑串扰
IF 14.7 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-10-31 DOI: 10.1016/j.neuron.2024.10.009
Jonathan W Lovelace, Jingrui Ma, Vineet Augustine

Interoception, the sensation and perception of internal bodily states, should be conceptualized through specialized modalities like cardioception, pulmoception, gastroception, and uroception. This NeuroView emphasizes cardioception, exploring heart-brain interactions, cardiac reflexes, and their influence on mental states and behavior.

内感知是对身体内部状态的感觉和知觉,应通过心感知、脉搏感知、胃感知和尿感知等专门模式加以概念化。本神经观强调心感,探讨心脑互动、心脏反射及其对心理状态和行为的影响。
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引用次数: 0
Inhibition of RNA splicing triggers CHMP7 nuclear entry, impacting TDP-43 function and leading to the onset of ALS cellular phenotypes. 抑制 RNA 剪接会触发 CHMP7 进入细胞核,影响 TDP-43 的功能,导致 ALS 细胞表型的出现。
IF 14.7 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-10-31 DOI: 10.1016/j.neuron.2024.10.007
Norah Al-Azzam, Jenny H To, Vaishali Gautam, Lena A Street, Chloe B Nguyen, Jack T Naritomi, Dylan C Lam, Assael A Madrigal, Benjamin Lee, Wenhao Jin, Anthony Avina, Orel Mizrahi, Jasmine R Mueller, Willard Ford, Cara R Schiavon, Elena Rebollo, Anthony Q Vu, Steven M Blue, Yashwin L Madakamutil, Uri Manor, Jeffrey D Rothstein, Alyssa N Coyne, Marko Jovanovic, Gene W Yeo

Amyotrophic lateral sclerosis (ALS) is linked to the reduction of certain nucleoporins in neurons. Increased nuclear localization of charged multivesicular body protein 7 (CHMP7), a protein involved in nuclear pore surveillance, has been identified as a key factor damaging nuclear pores and disrupting transport. Using CRISPR-based microRaft, followed by gRNA identification (CRaft-ID), we discovered 55 RNA-binding proteins (RBPs) that influence CHMP7 localization, including SmD1, a survival of motor neuron (SMN) complex component. Immunoprecipitation-mass spectrometry (IP-MS) and enhanced crosslinking and immunoprecipitation (CLIP) analyses revealed CHMP7's interactions with SmD1, small nuclear RNAs, and splicing factor mRNAs in motor neurons (MNs). ALS induced pluripotent stem cell (iPSC)-MNs show reduced SmD1 expression, and inhibiting SmD1/SMN complex increased CHMP7 nuclear localization. Crucially, overexpressing SmD1 in ALS iPSC-MNs restored CHMP7's cytoplasmic localization and corrected STMN2 splicing. Our findings suggest that early ALS pathogenesis is driven by SMN complex dysregulation.

肌萎缩性脊髓侧索硬化症(ALS)与神经元中某些核蛋白的减少有关。带电多囊体蛋白 7(CHMP7)是一种参与核孔监控的蛋白质,它的核定位增加已被确定为破坏核孔和干扰运输的一个关键因素。利用基于 CRISPR 的 microRaft 和 gRNA 鉴定(CRaft-ID),我们发现了 55 个影响 CHMP7 定位的 RNA 结合蛋白(RBPs),其中包括运动神经元(SMN)生存复合体成分 SmD1。免疫沉淀-质谱(IP-MS)和增强交联与免疫沉淀(CLIP)分析揭示了CHMP7与运动神经元(MNs)中的SmD1、小核RNA和剪接因子mRNA的相互作用。ALS 诱导多能干细胞(iPSC)-MNs 显示 SmD1 表达减少,抑制 SmD1/SMN 复合物可增加 CHMP7 的核定位。重要的是,在ALS iPSC-MNs中过表达SmD1可恢复CHMP7的胞浆定位并纠正STMN2的剪接。我们的研究结果表明,ALS 早期发病机制是由 SMN 复合物失调驱动的。
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引用次数: 0
Zero-shot counting with a dual-stream neural network model. 利用双流神经网络模型进行零点计数。
IF 14.7 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-10-29 DOI: 10.1016/j.neuron.2024.10.008
Jessica A F Thompson, Hannah Sheahan, Tsvetomira Dumbalska, Julian D Sandbrink, Manuela Piazza, Christopher Summerfield

To understand a visual scene, observers need to both recognize objects and encode relational structure. For example, a scene comprising three apples requires the observer to encode concepts of "apple" and "three." In the primate brain, these functions rely on dual (ventral and dorsal) processing streams. Object recognition in primates has been successfully modeled with deep neural networks, but how scene structure (including numerosity) is encoded remains poorly understood. Here, we built a deep learning model, based on the dual-stream architecture of the primate brain, which is able to count items "zero-shot"-even if the objects themselves are unfamiliar. Our dual-stream network forms spatial response fields and lognormal number codes that resemble those observed in the macaque posterior parietal cortex. The dual-stream network also makes successful predictions about human counting behavior. Our results provide evidence for an enactive theory of the role of the posterior parietal cortex in visual scene understanding.

要理解一个视觉场景,观察者需要同时识别物体和编码关系结构。例如,一个由三个苹果组成的场景需要观察者编码 "苹果 "和 "三 "的概念。在灵长类动物的大脑中,这些功能依赖于双重(腹侧和背侧)处理流。深度神经网络已成功模拟了灵长类动物的物体识别,但对于如何编码场景结构(包括数字)仍知之甚少。在这里,我们基于灵长类动物大脑的双流架构建立了一个深度学习模型,该模型能够 "零距离 "计数物品--即使物品本身并不熟悉。我们的双流网络形成的空间响应场和对数正态数字编码与在猕猴后顶叶皮层观察到的类似。双流网络还成功预测了人类的计数行为。我们的研究结果为后顶叶皮层在视觉场景理解中的作用的能动理论提供了证据。
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引用次数: 0
Functional architecture of cerebral cortex during naturalistic movie watching. 自然观影过程中大脑皮层的功能结构。
IF 14.7 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-10-25 DOI: 10.1016/j.neuron.2024.10.005
Reza Rajimehr, Haoran Xu, Asa Farahani, Simon Kornblith, John Duncan, Robert Desimone

Characterizing the functional organization of cerebral cortex is a fundamental step in understanding how different kinds of information are processed in the brain. However, it is still unclear how these areas are organized during naturalistic visual and auditory stimulation. Here, we used high-resolution functional MRI data from 176 human subjects to map the macro-architecture of the entire cerebral cortex based on responses to a 60-min audiovisual movie stimulus. A data-driven clustering approach revealed a map of 24 functional areas/networks, each explicitly linked to a specific aspect of sensory or cognitive processing. Novel features of this map included an extended scene-selective network in the lateral prefrontal cortex, separate clusters responsive to human-object and human-human interaction, and a push-pull interaction between three executive control (domain-general) networks and domain-specific regions of the visual, auditory, and language cortex. Our cortical parcellation provides a comprehensive and unified map of functionally defined areas in the human cerebral cortex.

描述大脑皮层的功能组织是了解大脑如何处理各种信息的基本步骤。然而,目前还不清楚这些区域在自然视觉和听觉刺激时是如何组织的。在这里,我们利用 176 名人类受试者的高分辨率功能磁共振成像数据,根据他们对 60 分钟视听电影刺激的反应,绘制了整个大脑皮层的宏观架构图。数据驱动的聚类方法揭示了由 24 个功能区/网络组成的地图,每个功能区/网络都与感官或认知处理的特定方面明确相关。该图谱的新特征包括外侧前额叶皮层中的扩展场景选择网络、对人-物和人-人互动做出反应的独立群组,以及三个执行控制(领域一般)网络与视觉、听觉和语言皮层的特定领域区域之间的推拉互动。我们的大脑皮层划分为人类大脑皮层功能定义区域提供了一个全面而统一的地图。
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引用次数: 0
Environmental complexity modulates information processing and the balance between decision-making systems. 环境的复杂性会调节信息处理和决策系统之间的平衡。
IF 14.7 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-10-24 DOI: 10.1016/j.neuron.2024.10.004
Ugurcan Mugan, Samantha L Hoffman, A David Redish

Behavior in naturalistic scenarios occurs in diverse environments. Adaptive strategies rely on multiple neural circuits and competing decision systems. However, past studies of rodent decision making have largely measured behavior in simple environments. To fill this gap, we recorded neural ensembles from hippocampus (HC), dorsolateral striatum (DLS), and dorsomedial prefrontal cortex (dmPFC) while rats foraged for food under changing rules in environments with varying topological complexity. Environmental complexity increased behavioral variability, lengthened HC nonlocal sequences, and modulated action caching. We found contrasting representations between DLS and HC, supporting a competition between decision systems. dmPFC activity was indicative of setting this balance, in particular predicting the extent of HC non-local coding. Inactivating mPFC impaired short-term behavioral adaptation and produced long-term deficits in balancing decision systems. Our findings reveal the dynamic nature of decision-making systems and how environmental complexity modulates their engagement with implications for behavior in naturalistic environments.

自然场景中的行为发生在不同的环境中。适应策略依赖于多个神经回路和相互竞争的决策系统。然而,过去对啮齿动物决策制定的研究大多是在简单环境中测量行为。为了填补这一空白,我们记录了海马(HC)、背外侧纹状体(DLS)和背内侧前额叶皮层(dmPFC)的神经集合,当时大鼠正在拓扑复杂程度不同的环境中根据不断变化的规则觅食。环境的复杂性增加了行为的可变性,延长了HC非局部序列,并调节了动作缓存。我们发现 DLS 和 HC 之间的表征形成了鲜明对比,这支持了决策系统之间的竞争。dmPFC 的活动表明了这种平衡的设定,尤其是预测 HC 非本地编码的程度。使 mPFC 失活会损害短期行为适应,并产生平衡决策系统的长期缺陷。我们的研究结果揭示了决策系统的动态性质,以及环境复杂性如何调节决策系统的参与,并对自然环境中的行为产生影响。
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引用次数: 0
When rewards backfire: Collapsing under pressure in motor cortex. 当奖励适得其反时运动皮层在压力下崩溃
IF 14.7 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-10-23 DOI: 10.1016/j.neuron.2024.09.022
Mojtaba Abbaszadeh, Becket Ebitz

People often underperform their abilities in high-value situations, a mysterious phenomenon known as "choking under pressure." In this issue of Neuron, Smoulder et al.1 report that target-selective signals in the motor cortex of non-human primates collapse in the face of high-value opportunities.

人们经常在高价值的情况下发挥不出自己的能力,这种神秘现象被称为 "压力下的窒息"。在本期《神经元》(Neuron)杂志上,Smoulder 等人1 报告说,非人灵长类动物运动皮层的目标选择信号在面对高价值机会时会崩溃。
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引用次数: 0
Motor cortex is responsible for motoric dynamics in striatum and the execution of both skilled and unskilled actions. 运动皮层负责纹状体的运动动力以及熟练和非熟练动作的执行。
IF 14.7 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-10-23 Epub Date: 2024-08-20 DOI: 10.1016/j.neuron.2024.07.022
Mark A Nicholas, Eric A Yttri

Striatum and its predominant input, motor cortex, are responsible for the selection and performance of purposive movement, but how their interaction guides these processes is not understood. To establish its neural and behavioral contributions, we bilaterally lesioned motor cortex and recorded striatal activity and reaching performance daily, capturing the lesion's direct ramifications within hours of the intervention. We observed reaching impairment and an absence of striatal motoric activity following lesion of motor cortex, but not parietal cortex control lesions. Although some aspects of performance began to recover after 8-10 days, striatal projection and interneuronal dynamics did not-eventually entering a non-motor encoding state that aligned with persisting kinematic control deficits. Lesioned mice also exhibited a profound inability to switch motor plans while locomoting, reminiscent of clinical freezing of gait (FOG). Our results demonstrate the necessity of motor cortex in generating trained and untrained actions as well as striatal motoric dynamics.

纹状体及其主要输入--运动皮层--负责选择和执行目的性运动,但它们之间的相互作用如何引导这些过程尚不清楚。为了确定纹状体对神经和行为的贡献,我们对运动皮层进行了双侧病变,并记录了纹状体的活动和每天的伸手动作,从而捕捉到了病变在干预后数小时内的直接影响。我们观察到,运动皮层病变后会出现伸手障碍和纹状体运动活动缺失,而顶叶皮层对照组病变后则不会出现这种情况。虽然某些方面的表现在 8-10 天后开始恢复,但纹状体投射和神经元间动力学并未恢复--最终进入非运动编码状态,与持续的运动控制缺陷相一致。受损伤的小鼠在运动时还表现出极度的运动计划切换能力,这让人联想到临床上的步态冻结(FOG)。我们的研究结果证明了运动皮层在产生训练和非训练动作以及纹状体运动动力学方面的必要性。
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引用次数: 0
Neurobehavioral meaning of pupil size. 瞳孔大小的神经行为学意义。
IF 14.7 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-10-23 Epub Date: 2024-06-25 DOI: 10.1016/j.neuron.2024.05.029
Nikola Grujic, Rafael Polania, Denis Burdakov

Pupil size is a widely used metric of brain state. It is one of the few signals originating from the brain that can be readily monitored with low-cost devices in basic science, clinical, and home settings. It is, therefore, important to investigate and generate well-defined theories related to specific interpretations of this metric. What exactly does it tell us about the brain? Pupils constrict in response to light and dilate during darkness, but the brain also controls pupil size irrespective of luminosity. Pupil size fluctuations resulting from ongoing "brain states" are used as a metric of arousal, but what is pupil-linked arousal and how should it be interpreted in neural, cognitive, and computational terms? Here, we discuss some recent findings related to these issues. We identify open questions and propose how to answer them through a combination of well-defined tasks, neurocomputational models, and neurophysiological probing of the interconnected loops of causes and consequences of pupil size.

瞳孔大小是衡量大脑状态的一个广泛应用的指标。在基础科学、临床和家庭环境中,它是少数几个可以通过低成本设备随时监测的大脑信号之一。因此,研究并提出与这一指标的具体解释相关的定义明确的理论非常重要。它究竟能告诉我们大脑的哪些信息?瞳孔在光照下收缩,在黑暗中扩张,但大脑也会控制瞳孔的大小,与光度无关。持续的 "大脑状态 "导致的瞳孔大小波动被用作唤醒的度量标准,但什么是与瞳孔相关的唤醒,又该如何从神经、认知和计算的角度对其进行解释?在此,我们将讨论与这些问题相关的一些最新发现。我们确定了一些开放性问题,并提出了如何通过结合定义明确的任务、神经计算模型和神经生理学探究瞳孔大小前因后果的相互关联回路来回答这些问题。
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引用次数: 0
Molecular and circuit determinants in the globus pallidus mediating control of cocaine-induced behavioral plasticity. 苍白球介导可卡因诱导行为可塑性控制的分子和回路决定因素
IF 14.7 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-10-23 Epub Date: 2024-08-16 DOI: 10.1016/j.neuron.2024.07.018
Guilian Tian, Katrina Bartas, May Hui, Lingxuan Chen, Jose J Vasquez, Ghalia Azouz, Pieter Derdeyn, Rían W Manville, Erick L Ho, Amanda S Fang, Yuan Li, Isabella Tyler, Vincent Setola, Jason Aoto, Geoffrey W Abbott, Kevin T Beier

The globus pallidus externus (GPe) is a central component of the basal ganglia circuit that acts as a gatekeeper of cocaine-induced behavioral plasticity. However, the molecular and circuit mechanisms underlying this function are unknown. Here, we show that GPe parvalbumin-positive (GPePV) cells mediate cocaine responses by selectively modulating ventral tegmental area dopamine (VTADA) cells projecting to the dorsomedial striatum (DMS). Interestingly, GPePV cell activity in cocaine-naive mice is correlated with behavioral responses following cocaine, effectively predicting cocaine sensitivity. Expression of the voltage-gated potassium channels KCNQ3 and KCNQ5 that control intrinsic cellular excitability following cocaine was downregulated, contributing to the elevation in GPePV cell excitability. Acutely activating channels containing KCNQ3 and/or KCNQ5 using the small molecule carnosic acid, a key psychoactive component of Salvia rosmarinus (rosemary) extract, reduced GPePV cell excitability and impaired cocaine reward, sensitization, and volitional cocaine intake, indicating its therapeutic potential to counteract psychostimulant use disorder.

苍白球外侧(GPe)是基底神经节回路的核心组成部分,是可卡因诱导的行为可塑性的看门人。然而,这一功能的分子和回路机制尚不清楚。在这里,我们发现 GPe 副发光素阳性(GPePV)细胞通过选择性调节投射到背内侧纹状体(DMS)的腹侧被盖区多巴胺(VTADA)细胞来介导可卡因反应。有趣的是,对可卡因无反应的小鼠体内 GPePV 细胞的活性与服用可卡因后的行为反应相关,从而有效地预测了对可卡因的敏感性。电压门控钾通道 KCNQ3 和 KCNQ5 的表达下调,而 KCNQ3 和 KCNQ5 控制着可卡因后的细胞固有兴奋性,从而导致 GPePV 细胞兴奋性的升高。小分子肉毒碱是迷迭香提取物(Salvia rosinus (rosemary) extract)中的一种主要精神活性成分,使用这种小分子肉毒碱急性激活含有KCNQ3和/或KCNQ5的通道可降低GPePV细胞的兴奋性,并损害可卡因奖赏、敏感性和自愿摄入可卡因的能力,这表明肉毒碱具有对抗精神兴奋剂使用障碍的治疗潜力。
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引用次数: 0
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Neuron
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