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This Week in The Journal 本周华尔街日报
Pub Date : 2023-03-29 DOI: 10.1056/NEJMtwj230105
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引用次数: 0
This Week in The Journal 本周华尔街日报
Pub Date : 2023-03-29 DOI: 10.1523/jneurosci.twij.43.13.2023
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引用次数: 0
This Week in The Journal 本周华尔街日报
Pub Date : 2023-03-22 DOI: 10.1523/JNEUROSCI.twij.43.12.2023
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引用次数: 0
This Week in The Journal 本周华尔街日报
Pub Date : 2023-03-15 DOI: 10.1523/JNEUROSCI.twij.43.11.2023
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引用次数: 0
Basolateral Amygdala Astrocytes Are Engaged by the Acquisition and Expression of a Contextual Fear Memory 杏仁核基底外侧星形胶质细胞参与情境恐惧记忆的获取和表达
Pub Date : 2023-03-14 DOI: 10.1101/2022.09.11.507456
R. L. Suthard, R. Senne, Michelle D. Buzharsky, Angela Y. Pyo, Kaitlyn E. Dorst, A. H. Diep, Rebecca H. Cole, S. Ramirez
Astrocytes are key cellular regulators within the brain. The basolateral amygdala (BLA) is implicated in fear memory processing, yet most research has entirely focused on neuronal mechanisms, despite a significant body of work implicating astrocytes in learning and memory. In the present study, we used in vivo fiber photometry in C57BL/6J male mice to record from amygdalar astrocytes across fear learning, recall, and three separate periods of extinction. We found that BLA astrocytes robustly responded to foot shock during acquisition, their activity remained remarkably elevated across days in comparison to unshocked control animals, and their increased activity persisted throughout extinction. Further, we found that astrocytes responded to the initiation and termination of freezing bouts during contextual fear conditioning and recall, and this behavior-locked pattern of activity did not persist throughout the extinction sessions. Importantly, astrocytes do not display these changes while exploring a novel context, suggesting that these observations are specific to the original fear-associated environment. Chemogenetic inhibition of fear ensembles in the BLA did not affect freezing behavior or astrocytic calcium dynamics. Overall, our work presents a real-time role for amygdalar astrocytes in fear processing and provides new insight into the emerging role of these cells in cognition and behavior. SIGNIFICANCE STATEMENT We show that basolateral amygdala astrocytes are robustly responsive to negative experiences, like shock, and display changed calcium activity patterns through fear learning and memory. Additionally, astrocytic calcium responses become time locked to the initiation and termination of freezing behavior during fear learning and recall. We find that astrocytes display calcium dynamics unique to a fear-conditioned context, and chemogenetic inhibition of BLA fear ensembles does not have an impact on freezing behavior or calcium dynamics. These findings show that astrocytes play a key real-time role in fear learning and memory.
星形胶质细胞是大脑中关键的细胞调节器。基底外侧杏仁核(BLA)与恐惧记忆处理有关,尽管有大量的工作表明星形胶质细胞与学习和记忆有关,但大多数研究都集中在神经元机制上。在本研究中,我们使用体内纤维光度法记录了C57BL/6J雄性小鼠的杏仁核星形胶质细胞在恐惧学习、回忆和三个不同的消退时期的变化。我们发现,BLA星形胶质细胞在获得足部电击时反应强烈,与未受到电击的对照动物相比,它们的活性在数天内保持显著升高,并且在灭绝过程中它们的活性持续增加。此外,我们发现星形胶质细胞在情境恐惧条件反射和回忆过程中对冻结发作的开始和结束作出反应,而这种行为锁定的活动模式在整个消失过程中并不持续。重要的是,星形胶质细胞在探索新环境时不会表现出这些变化,这表明这些观察结果是特定于原始恐惧相关环境的。BLA中恐惧集合的化学发生抑制不影响冻结行为或星形细胞钙动力学。总的来说,我们的工作展示了杏仁核星形胶质细胞在恐惧处理中的实时作用,并为这些细胞在认知和行为中的新兴作用提供了新的见解。我们发现杏仁核基底外侧星形胶质细胞对负面经历(如休克)有强烈的反应,并通过恐惧、学习和记忆显示钙活性模式的改变。此外,星形细胞钙反应在恐惧学习和回忆过程中被冻结行为的开始和终止所锁定。我们发现星形胶质细胞在恐惧条件下表现出独特的钙动力学,BLA恐惧集合的化学发生抑制对冻结行为或钙动力学没有影响。这些发现表明星形胶质细胞在恐惧学习和记忆中起着关键的实时作用。
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引用次数: 2
Angular Gyrus Responses Show Joint Statistical Dependence with Brain Regions Selective for Different Categories 角回反应在统计上与不同类别的脑区选择性相关
Pub Date : 2023-03-09 DOI: 10.32470/ccn.2022.1036-0
Mengting Fang, Aidas Aglinskas, Yichen Li, Stefano Anzellotti
Category selectivity is a fundamental principle of organization of perceptual brain regions. Human occipitotemporal cortex is subdivided into areas that respond preferentially to faces, bodies, artifacts, and scenes. However, observers need to combine information about objects from different categories to form a coherent understanding of the world. How is this multicategory information encoded in the brain? Studying the multivariate interactions between brain regions of male and female human subjects with fMRI and artificial neural networks, we found that the angular gyrus shows joint statistical dependence with multiple category-selective regions. Adjacent regions show effects for the combination of scenes and each other category, suggesting that scenes provide a context to combine information about the world. Additional analyses revealed a cortical map of areas that encode information across different subsets of categories, indicating that multicategory information is not encoded in a single centralized location, but in multiple distinct brain regions. SIGNIFICANCE STATEMENT Many cognitive tasks require combining information about entities from different categories. However, visual information about different categorical objects is processed by separate, specialized brain regions. How is the joint representation from multiple category-selective regions implemented in the brain? Using fMRI movie data and state-of-the-art multivariate statistical dependence based on artificial neural networks, we identified the angular gyrus encoding responses across face-, body-, artifact-, and scene-selective regions. Further, we showed a cortical map of areas that encode information across different subsets of categories. These findings suggest that multicategory information is not encoded in a single centralized location, but at multiple cortical sites which might contribute to distinct cognitive functions, offering insights to understand integration in a variety of domains.
类别选择性是大脑知觉区域组织的基本原则。人的枕颞皮层被细分为对面孔、身体、人工制品和场景有优先反应的区域。然而,观察者需要将来自不同类别的物体的信息结合起来,形成对世界的连贯理解。这种多类别信息是如何在大脑中编码的?利用功能磁共振成像(fMRI)和人工神经网络研究男女受试者脑区之间的多元相互作用,发现角回与多个类别选择区域具有联合统计依赖性。相邻区域显示了场景和其他类别组合的效果,表明场景提供了一个环境来组合关于世界的信息。进一步的分析揭示了大脑皮层中编码不同类别子集信息的区域图,表明多类别信息不是在一个单一的集中位置编码的,而是在多个不同的大脑区域编码的。许多认知任务需要组合来自不同类别的实体信息。然而,关于不同分类对象的视觉信息是由单独的、专门的大脑区域处理的。来自多个类别选择区域的联合表征是如何在大脑中实现的?利用fMRI电影数据和基于人工神经网络的最先进的多元统计依赖,我们确定了角回编码面部、身体、伪影和场景选择区域的响应。此外,我们还展示了跨不同类别子集编码信息的皮质区域图。这些发现表明,多类别信息不是在一个单一的集中位置编码的,而是在多个皮质区域编码的,这些区域可能有助于不同的认知功能,为理解各种领域的整合提供了见解。
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引用次数: 1
Decreased Ventral Tegmental Area CB1R Signaling Reduces Sign Tracking and Shifts Cue–Outcome Dynamics in Rat Nucleus Accumbens 腹侧被盖区CB1R信号的减少减少了信号跟踪并改变了大鼠伏隔核的线索-结果动力学
Pub Date : 2023-03-09 DOI: 10.1101/2022.07.22.501038
Sam Z. Bacharach, David A. Martin, Cassie A. Stapf, Fangmiao Sun, Yulong Li, J. Cheer, Donna J. Calu
Sign-tracking (ST) rats show enhanced cue sensitivity before drug experience that predicts greater discrete cue-induced drug seeking compared with goal-tracking or intermediate rats. Cue-evoked dopamine in the nucleus accumbens (NAc) is a neurobiological signature of sign-tracking behaviors. Here, we examine a critical regulator of the dopamine system, endocannabinoids, which bind the cannabinoid receptor-1 (CB1R) in the ventral tegmental area (VTA) to control cue-evoked striatal dopamine levels. We use cell type-specific optogenetics, intra-VTA pharmacology, and fiber photometry to test the hypothesis that VTA CB1R receptor signaling regulates NAc dopamine levels to control sign tracking. We trained male and female rats in a Pavlovian lever autoshaping (PLA) task to determine their tracking groups before testing the effect of VTA → NAc dopamine inhibition. We found that this circuit is critical for mediating the vigor of the ST response. Upstream of this circuit, intra-VTA infusions of rimonabant, a CB1R inverse agonist, during PLA decrease lever and increase food cup approach in sign-trackers. Using fiber photometry to measure fluorescent signals from a dopamine sensor, GRABDA (AAV9-hSyn-DA2m), we tested the effects of intra-VTA rimonabant on NAc dopamine dynamics during autoshaping in female rats. We found that intra-VTA rimonabant decreased sign-tracking behaviors, which was associated with increases in NAc shell, but not core, dopamine levels during reward delivery [unconditioned stimulus (US)]. Our results suggest that CB1R signaling in the VTA influences the balance between the conditioned stimulus-evoked and US-evoked dopamine responses in the NAc shell and biases behavioral responding to cues in sign-tracking rats. SIGNIFICANCE STATEMENT Substance use disorder (SUD) is a chronically relapsing psychological disorder that affects a subset of individuals who engage in drug use. Recent research suggests that there are individual behavioral and neurobiological differences before drug experience that predict SUD and relapse vulnerabilities. Here, we investigate how midbrain endocannabinoids regulate a brain pathway that is exclusively involved in driving cue-motivated behaviors of sign-tracking rats. This work contributes to our mechanistic understanding of individual vulnerabilities to cue-triggered natural reward seeking that have relevance for drug-motivated behaviors.
与目标跟踪大鼠或中间大鼠相比,信号跟踪大鼠在药物体验前表现出增强的线索敏感性,预测更大的离散线索诱导的药物寻找。伏隔核(NAc)的线索诱发多巴胺是信号跟踪行为的神经生物学特征。在这里,我们研究了多巴胺系统的一个关键调节因子,内源性大麻素,它结合腹侧被盖区(VTA)的大麻素受体-1 (CB1R)来控制线索诱发的纹状体多巴胺水平。我们使用细胞类型特异性光遗传学,VTA内药理学和纤维光度法来验证VTA CB1R受体信号调节NAc多巴胺水平以控制信号跟踪的假设。在测试VTA→NAc多巴胺抑制的效果之前,我们在巴甫洛夫杠杆自动塑造(PLA)任务中训练雄性和雌性大鼠,以确定它们的跟踪组。我们发现这个回路对于调节ST反应的活力至关重要。在该回路的上游,在信号追踪器的PLA降低水平和增加食物杯方法中,在vta内输注利莫那班(一种CB1R逆激动剂)。利用纤维光度法测量多巴胺传感器GRABDA (AAV9-hSyn-DA2m)的荧光信号,我们测试了vta内利莫那班对雌性大鼠自动成型过程中NAc多巴胺动态的影响。我们发现,vta内利莫那班减少了信号跟踪行为,这与奖励传递过程中NAc壳(而非核心)多巴胺水平的增加有关[非条件刺激(US)]。我们的研究结果表明,VTA中的CB1R信号影响了NAc壳中条件刺激诱发和美国诱发的多巴胺反应之间的平衡,并影响了信号追踪大鼠对线索的行为反应。物质使用障碍(SUD)是一种慢性复发的心理障碍,影响了一部分从事药物使用的个体。最近的研究表明,在药物经历之前存在个体行为和神经生物学差异,可以预测SUD和复发的脆弱性。在这里,我们研究了中脑内源性大麻素如何调节一个专门参与驱动信号跟踪大鼠的线索动机行为的脑通路。这项工作有助于我们对线索触发的自然奖励寻求与药物动机行为相关的个体脆弱性的机制理解。
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引用次数: 0
This Week in The Journal 本周华尔街日报
Pub Date : 2023-03-08 DOI: 10.1523/JNEUROSCI.twij.43.10.2023
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引用次数: 0
Dimensionality and Ramping: Signatures of Sentence Integration in the Dynamics of Brains and Deep Language Models 维度与斜坡:脑动力学与深度语言模型中句子整合的特征
Pub Date : 2023-03-01 DOI: 10.1101/2023.02.28.530443
T. Desbordes, Yair Lakretz, V. Chanoine, M. Oquab, J. Badier, A. Trébuchon, R. Carron, C. Bénar, S. Dehaene, J. King
A sentence is more than the sum of its words: its meaning depends on how they combine with one another. The brain mechanisms underlying such semantic composition remain poorly understood. To shed light on the neural vector code underlying semantic composition, we introduce two hypotheses: (1) the intrinsic dimensionality of the space of neural representations should increase as a sentence unfolds, paralleling the growing complexity of its semantic representation; and (2) this progressive integration should be reflected in ramping and sentence-final signals. To test these predictions, we designed a dataset of closely matched normal and jabberwocky sentences (composed of meaningless pseudo words) and displayed them to deep language models and to 11 human participants (5 men and 6 women) monitored with simultaneous MEG and intracranial EEG. In both deep language models and electrophysiological data, we found that representational dimensionality was higher for meaningful sentences than jabberwocky. Furthermore, multivariate decoding of normal versus jabberwocky confirmed three dynamic patterns: (1) a phasic pattern following each word, peaking in temporal and parietal areas; (2) a ramping pattern, characteristic of bilateral inferior and middle frontal gyri; and (3) a sentence-final pattern in left superior frontal gyrus and right orbitofrontal cortex. These results provide a first glimpse into the neural geometry of semantic integration and constrain the search for a neural code of linguistic composition. SIGNIFICANCE STATEMENT Starting from general linguistic concepts, we make two sets of predictions in neural signals evoked by reading multiword sentences. First, the intrinsic dimensionality of the representation should grow with additional meaningful words. Second, the neural dynamics should exhibit signatures of encoding, maintaining, and resolving semantic composition. We successfully validated these hypotheses in deep neural language models, artificial neural networks trained on text and performing very well on many natural language processing tasks. Then, using a unique combination of MEG and intracranial electrodes, we recorded high-resolution brain data from human participants while they read a controlled set of sentences. Time-resolved dimensionality analysis showed increasing dimensionality with meaning, and multivariate decoding allowed us to isolate the three dynamical patterns we had hypothesized.
一个句子不仅仅是单词的总和,它的意义取决于单词如何相互组合。这种语义构成背后的大脑机制仍然知之甚少。为了阐明语义构成背后的神经向量代码,我们引入了两个假设:(1)随着句子的展开,神经表征空间的内在维度应该增加,与语义表征的复杂性并行;(2)这种渐进式的整合应该体现在斜坡和句末信号上。为了验证这些预测,我们设计了一个紧密匹配的正常和胡言乱语句子(由无意义的伪词组成)的数据集,并将它们展示给深度语言模型和11名人类参与者(5名男性和6名女性),同时监测MEG和颅内脑电图。在深度语言模型和电生理数据中,我们发现有意义句子的表征维数高于废话句子。此外,正常和废话的多变量解码证实了三种动态模式:(1)每个单词之后都有一个相位模式,在颞叶和顶叶区域达到峰值;(2)双侧额下回和额中回呈斜坡状;(3)左侧额上回和右侧眼窝额叶皮层的句末模式。这些结果提供了对语义整合的神经几何的第一次一瞥,并限制了对语言组成的神经代码的搜索。我们从一般的语言学概念出发,对阅读多词句子所引起的神经信号进行了两组预测。首先,表征的内在维度应该随着额外的有意义的词语而增长。其次,神经动力学应该表现出编码、维护和解析语义组成的特征。我们成功地在深度神经语言模型中验证了这些假设,在文本上训练的人工神经网络在许多自然语言处理任务上表现得很好。然后,使用MEG和颅内电极的独特组合,我们记录了人类参与者在阅读一组受控句子时的高分辨率大脑数据。时间分辨维度分析显示维度随意义的增加而增加,多元解码使我们能够分离出我们假设的三种动态模式。
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引用次数: 4
This Week in The Journal 本周华尔街日报
Pub Date : 2023-03-01 DOI: 10.1523/JNEUROSCI.twij.43.9.2023
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引用次数: 0
期刊
The Journal of Neuroscience
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