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Learning, Fast and Slow: Single- and Many-Shot Learning in the Hippocampus. 学习,快与慢》:海马体的单次学习和多次学习
IF 13.9 1区 医学 Q1 Neuroscience Pub Date : 2024-04-25 DOI: 10.1146/annurev-neuro-102423-100258
Zhenrui Liao, A. Losonczy
The hippocampus is critical for memory and spatial navigation. The ability to map novel environments, as well as more abstract conceptual relationships, is fundamental to the cognitive flexibility that humans and other animals require to survive in a dynamic world. In this review, we survey recent advances in our understanding of how this flexibility is implemented anatomically and functionally by hippocampal circuitry, during both active exploration (online) and rest (offline). We discuss the advantages and limitations of spike timing-dependent plasticity and the more recently discovered behavioral timescale synaptic plasticity in supporting distinct learning modes in the hippocampus. Finally, we suggest complementary roles for these plasticity types in explaining many-shot and single-shot learning in the hippocampus and discuss how these rules could work together to support the learning of cognitive maps.
海马对记忆和空间导航至关重要。绘制新环境以及更抽象的概念关系图的能力是人类和其他动物在动态世界中生存所需的认知灵活性的基础。在这篇综述中,我们将探讨海马电路在积极探索(在线)和休息(离线)期间如何在解剖学和功能上实现这种灵活性的最新进展。我们讨论了尖峰计时可塑性和最近发现的行为时间尺度突触可塑性在支持海马不同学习模式方面的优势和局限性。最后,我们提出了这些可塑性类型在解释海马的多次学习和单次学习中的互补作用,并讨论了这些规则如何共同支持认知地图的学习。
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引用次数: 0
Cerebellar Functions Beyond Movement and Learning. 运动和学习之外的小脑功能
IF 13.9 1区 医学 Q1 Neuroscience Pub Date : 2024-04-25 DOI: 10.1146/annurev-neuro-100423-104943
Linda H Kim, Detlef H Heck, R. Sillitoe
The cerebellum has a well-established role in controlling motor functions, including coordination, posture, and the learning of skilled movements. The mechanisms for how it carries out motor behavior remain under intense investigation. Interestingly though, in recent years the mechanisms of cerebellar function have faced additional scrutiny since nonmotor behaviors may also be controlled by the cerebellum. With such complexity arising, there is now a pressing need to better understand how cerebellar structure, function, and behavior intersect to influence behaviors that are dynamically called upon as an animal experiences its environment. Here, we discuss recent experimental work that frames possible neural mechanisms for how the cerebellum shapes disparate behaviors and why its dysfunction is catastrophic in hereditary and acquired conditions-both motor and nonmotor. For these reasons, the cerebellum might be the ideal therapeutic target.
小脑在控制运动功能(包括协调、姿势和学习熟练动作)方面的作用已得到公认。关于小脑如何执行运动行为的机制仍在深入研究中。但有趣的是,近年来小脑功能的机制受到了更多的关注,因为非运动行为也可能由小脑控制。随着这种复杂性的出现,现在迫切需要更好地了解小脑结构、功能和行为是如何相互交织以影响动物在体验其环境时动态调用的行为的。在这里,我们将讨论最近的实验工作,这些工作构建了小脑塑造不同行为的可能神经机制,以及小脑功能障碍在遗传性和获得性疾病(包括运动性和非运动性疾病)中造成灾难性后果的原因。由于这些原因,小脑可能是理想的治疗目标。
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引用次数: 0
Meningeal Lymphatics in Central Nervous System Diseases. 中枢神经系统疾病中的脑膜淋巴管。
IF 13.9 1区 医学 Q1 Neuroscience Pub Date : 2024-04-22 DOI: 10.1146/annurev-neuro-113023-103045
A. F. Salvador, Nora Abduljawad, Jonathan Kipnis
Since its recent discovery, the meningeal lymphatic system has reshaped our understanding of central nervous system (CNS) fluid exchange, waste clearance, immune cell trafficking, and immune privilege. Meningeal lymphatics have also been demonstrated to functionally modify the outcome of neurological disorders and their responses to treatment, including brain tumors, inflammatory diseases such as multiple sclerosis, CNS injuries, and neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. In this review, we discuss recent evidence of the contribution of meningeal lymphatics to neurological diseases, as well as the available experimental methods for manipulating meningeal lymphatics in these conditions. Finally, we also provide a discussion of the pressing questions and challenges in utilizing meningeal lymphatics as a prime target for CNS therapeutic intervention and possibly drug delivery for brain disorders.
自从最近发现脑膜淋巴系统以来,它重塑了我们对中枢神经系统(CNS)液体交换、废物清除、免疫细胞贩运和免疫特权的认识。脑膜淋巴管还被证明能在功能上改变神经系统疾病的结果及其对治疗的反应,包括脑肿瘤、多发性硬化等炎症性疾病、中枢神经系统损伤以及阿尔茨海默氏症和帕金森氏症等神经退行性疾病。在这篇综述中,我们将讨论脑膜淋巴管对神经系统疾病影响的最新证据,以及在这些疾病中操纵脑膜淋巴管的现有实验方法。最后,我们还讨论了在利用脑膜淋巴管作为中枢神经系统治疗干预的主要靶点以及可能用于脑部疾病的药物输送方面存在的紧迫问题和挑战。
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引用次数: 0
Development of the Binocular Circuit 双目电路的发展
IF 13.9 1区 医学 Q1 Neuroscience Pub Date : 2024-04-18 DOI: 10.1146/annurev-neuro-111020-093230
Eloísa Herrera, Alain Chédotal, Carol Mason
Seeing in three dimensions is a major property of the visual system in mammals. The circuit underlying this property begins in the retina, from which retinal ganglion cells (RGCs) extend to the same or opposite side of the brain. RGC axons decussate to form the optic chiasm, then grow to targets in the thalamus and midbrain, where they synapse with neurons that project to the visual cortex. Here we review the cellular and molecular mechanisms of RGC axonal growth cone guidance across or away from the midline via receptors to cues in the midline environment. We present new views on the specification of ipsi- and contralateral RGC subpopulations and factors implementing their organization in the optic tract and termination in subregions of their targets. Lastly, we describe the functional and behavioral aspects of binocular vision, focusing on the mouse, and discuss recent discoveries on the evolution of the binocular circuit.
立体视觉是哺乳动物视觉系统的一个主要特性。这一特性的基础回路始于视网膜,视网膜神经节细胞(RGC)从视网膜延伸到大脑的同侧或对侧。RGC 轴突决裂形成视交叉,然后向丘脑和中脑的目标生长,并在那里与投射到视觉皮层的神经元发生突触。在这里,我们回顾了 RGC 轴突生长锥通过中线环境中的线索受体跨越或远离中线的细胞和分子机制。我们就同侧和对侧RGC亚群的规格化及其在视束中的组织和在目标亚区域中的终止因素提出了新的观点。最后,我们以小鼠为重点,描述了双目视觉的功能和行为方面,并讨论了双目回路进化的最新发现。
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引用次数: 0
From Blur to Brilliance: The Ascendance of Advanced Microscopy in Neuronal Cell Biology 从模糊到辉煌:先进显微技术在神经元细胞生物学中的应用
IF 13.9 1区 医学 Q1 Neuroscience Pub Date : 2024-04-12 DOI: 10.1146/annurev-neuro-111020-090208
Kirby R. Campbell, Liam P. Hallada, Yu-Shan Huang, David J. Solecki
The intricate network of the brain's neurons and synapses poses unparalleled challenges for research, distinct from other biological studies. This is particularly true when dissecting how neurons and their functional units work at a cell biological level. While traditional microscopy has been foundational, it was unable to reveal the deeper complexities of neural interactions. However, an imaging renaissance has transformed our capabilities. Advancements in light and electron microscopy, combined with correlative imaging, now achieve unprecedented resolutions, uncovering the most nuanced neural structures. Maximizing these tools requires more than just technical proficiency. It is crucial to align research aims, allocate resources wisely, and analyze data effectively. At the heart of this evolution is interdisciplinary collaboration, where various experts come together to translate detailed imagery into significant biological insights. This review navigates the latest developments in microscopy, underscoring both the promise of and prerequisites for bending this powerful tool set to understanding neuronal cell biology.
大脑神经元和突触网络错综复杂,给研究带来了有别于其他生物研究的巨大挑战。在剖析神经元及其功能单元如何在细胞生物学水平上工作时尤其如此。传统的显微镜虽然具有奠基性作用,但却无法揭示神经相互作用更深层次的复杂性。然而,成像技术的复兴改变了我们的能力。光镜和电子显微镜技术的进步与相关成像技术相结合,实现了前所未有的分辨率,揭示了最细微的神经结构。最大限度地利用这些工具需要的不仅仅是精湛的技术。调整研究目标、合理分配资源和有效分析数据至关重要。跨学科合作是这一演变的核心,不同的专家汇聚一堂,将详细的图像转化为重要的生物学见解。这篇综述介绍了显微镜技术的最新发展,强调了利用这一强大工具集了解神经元细胞生物学的前景和先决条件。
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引用次数: 0
The Budding Neuroscience of Ant Social Behavior 蚂蚁社会行为的萌芽神经科学
IF 13.9 1区 医学 Q1 Neuroscience Pub Date : 2024-04-11 DOI: 10.1146/annurev-neuro-083023-102101
Dominic D. Frank, Daniel J.C. Kronauer
Ant physiology has been fashioned by 100 million years of social evolution. Ants perform many sophisticated social and collective behaviors yet possess nervous systems similar in schematic and scale to that of the fruit fly Drosophila melanogaster, a popular solitary model organism. Ants are thus attractive complementary subjects to investigate adaptations pertaining to complex social behaviors that are absent in flies. Despite research interest in ant behavior and the neurobiological foundations of sociality more broadly, our understanding of the ant nervous system is incomplete. Recent technical advances have enabled cutting-edge investigations of the nervous system in a fashion that is less dependent on model choice, opening the door for mechanistic social insect neuroscience. In this review, we revisit important aspects of what is known about the ant nervous system and behavior, and we look forward to how functional circuit neuroscience in ants will help us understand what distinguishes solitary animals from highly social ones.
一亿年的社会进化造就了蚂蚁的生理学。蚂蚁有许多复杂的社会和集体行为,但它们的神经系统在图式和规模上与果蝇(一种常用的单生模式生物)相似。因此,蚂蚁是研究复杂社会行为适应性的极具吸引力的互补对象,而这些适应性是果蝇所不具备的。尽管研究人员对蚂蚁行为和更广泛的社会性神经生物学基础很感兴趣,但我们对蚂蚁神经系统的了解还不全面。最近的技术进步使得神经系统的前沿研究不再那么依赖于模型的选择,从而为机制性社会昆虫神经科学打开了大门。在这篇综述中,我们将重新审视目前已知的蚂蚁神经系统和行为的重要方面,并期待蚂蚁的功能回路神经科学将如何帮助我们理解孤独动物与高度社会性动物的区别。
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引用次数: 0
Toward Optogenetic Hearing Restoration 实现光遗传学听力恢复
IF 13.9 1区 医学 Q1 Neuroscience Pub Date : 2024-04-10 DOI: 10.1146/annurev-neuro-070623-103247
Antoine Huet, Thomas Mager, Christian Gossler, Tobias Moser
The cochlear implant (CI) is considered the most successful neuroprosthesis as it enables speech comprehension in the majority of the million otherwise deaf patients. In hearing by electrical stimulation of the auditory nerve, the broad spread of current from each electrode acts as a bottleneck that limits the transfer of sound frequency information. Hence, there remains a major unmet medical need for improving the quality of hearing with CIs. Recently, optogenetic stimulation of the cochlea has been suggested as an alternative approach for hearing restoration. Cochlear optogenetics promises to transfer more sound frequency information, hence improving hearing, as light can conveniently be confined in space to activate the auditory nerve within smaller tonotopic ranges. In this review, we discuss the latest experimental and technological developments of optogenetic hearing restoration and outline remaining challenges en route to clinical translation.
人工耳蜗(CI)被认为是最成功的神经假体,因为它能让数百万耳聋患者中的大多数人理解语言。在通过电刺激听觉神经进行听力时,每个电极的电流传播范围很广,成为限制声频信息传递的瓶颈。因此,使用人工耳蜗提高听力质量仍是一项尚未满足的重大医疗需求。最近,有人建议将耳蜗光遗传学刺激作为恢复听力的另一种方法。耳蜗光遗传学有望传递更多的声频信息,从而改善听力,因为光可以方便地限制在空间内,在较小的声调范围内激活听觉神经。在这篇综述中,我们讨论了光遗传学听力恢复的最新实验和技术发展,并概述了临床转化过程中仍面临的挑战。
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引用次数: 0
Keeping Your Brain in Balance: Homeostatic Regulation of Network Function 保持大脑平衡:网络功能的平衡调节
IF 13.9 1区 医学 Q1 Neuroscience Pub Date : 2024-02-21 DOI: 10.1146/annurev-neuro-092523-110001
Wei Wen, Gina G. Turrigiano
To perform computations with the efficiency necessary for animal survival, neocortical microcircuits must be capable of reconfiguring in response to experience, while carefully regulating excitatory and inhibitory connectivity to maintain stable function. This dynamic fine-tuning is accomplished through a rich array of cellular homeostatic plasticity mechanisms that stabilize important cellular and network features such as firing rates, information flow, and sensory tuning properties. Further, these functional network properties can be stabilized by different forms of homeostatic plasticity, including mechanisms that target excitatory or inhibitory synapses, or that regulate intrinsic neuronal excitability. Here we discuss which aspects of neocortical circuit function are under homeostatic control, how this homeostasis is realized on the cellular and molecular levels, and the pathological consequences when circuit homeostasis is impaired. A remaining challenge is to elucidate how these diverse homeostatic mechanisms cooperate within complex circuits to enable them to be both flexible and stable.Expected final online publication date for the Annual Review of Neuroscience, Volume 47 is July 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
为了以动物生存所需的效率进行计算,新皮层微电路必须能够根据经验重新配置,同时仔细调节兴奋和抑制连接以保持功能稳定。这种动态微调是通过一系列丰富的细胞同态可塑性机制实现的,这些机制能稳定重要的细胞和网络特征,如发射率、信息流和感觉调谐特性。此外,这些功能性网络特性可以通过不同形式的同态可塑性得到稳定,包括针对兴奋性或抑制性突触的机制,或调节神经元内在兴奋性的机制。在此,我们将讨论新皮层回路功能的哪些方面受到同源性控制,这种同源性是如何在细胞和分子水平上实现的,以及回路同源性受损时的病理后果。余下的挑战是阐明这些不同的平衡机制如何在复杂的回路中合作,使它们既灵活又稳定。《神经科学年评》第 47 卷的最终在线出版日期预计为 2024 年 7 月。修订后的预计日期请参见 http://www.annualreviews.org/page/journal/pubdates。
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引用次数: 0
Neural Networks for Navigation: From Connections to Computations. 导航神经网络:从连接到计算。
IF 13.9 1区 医学 Q1 Neuroscience Pub Date : 2023-07-10 DOI: 10.1146/annurev-neuro-110920-032645
Rachel I Wilson

Many animals can navigate toward a goal they cannot see based on an internal representation of that goal in the brain's spatial maps. These maps are organized around networks with stable fixed-point dynamics (attractors), anchored to landmarks, and reciprocally connected to motor control. This review summarizes recent progress in understanding these networks, focusing on studies in arthropods. One factor driving recent progress is the availability of the Drosophila connectome; however, it is increasingly clear that navigation depends on ongoing synaptic plasticity in these networks. Functional synapses appear to be continually reselected from the set of anatomical potential synapses based on the interaction of Hebbian learning rules, sensory feedback, attractor dynamics, and neuromodulation. This can explain how the brain's maps of space are rapidly updated; it may also explain how the brain can initialize goals as stable fixed points for navigation.

许多动物可以根据大脑空间地图中目标的内部表征,导航到它们看不见的目标。这些地图围绕具有稳定的定点动力学(吸引子)的网络组织,锚定在地标上,并相互连接到电机控制。本文综述了近年来对这些网络的研究进展,重点介绍了节肢动物的研究。推动最近进展的一个因素是果蝇连接体的可用性;然而,越来越清楚的是,导航依赖于这些网络中正在进行的突触可塑性。基于Hebbian学习规则、感觉反馈、吸引子动力学和神经调节的相互作用,功能性突触似乎不断地从解剖学电位突触中被重新选择。这可以解释大脑的空间地图是如何快速更新的;这也可以解释大脑如何将目标初始化为导航的稳定固定点。
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引用次数: 4
Deep Brain Stimulation for Obsessive-Compulsive Disorder and Depression. 深部脑刺激治疗强迫症和抑郁症。
IF 13.9 1区 医学 Q1 Neuroscience Pub Date : 2023-07-10 DOI: 10.1146/annurev-neuro-110122-110434
Sameer A Sheth, Helen S Mayberg

The field of stereotactic neurosurgery developed more than 70 years ago to address a therapy gap for patients with severe psychiatric disorders. In the decades since, it has matured tremendously, benefiting from advances in clinical and basic sciences. Deep brain stimulation (DBS) for severe, treatment-resistant psychiatric disorders is currently poised to transition from a stage of empiricism to one increasingly rooted in scientific discovery. Current drivers of this transition are advances in neuroimaging, but rapidly emerging ones are neurophysiological-as we understand more about the neural basis of these disorders, we will more successfully be able to use interventions such as invasive stimulation to restore dysfunctional circuits to health. Paralleling this transition is a steady increase in the consistency and quality of outcome data. Here, we focus on obsessive-compulsive disorder and depression, two topics that have received the most attention in terms of trial volume and scientific effort.

立体定向神经外科领域在70多年前发展起来,以解决严重精神疾病患者的治疗差距。在此后的几十年里,得益于临床和基础科学的进步,它已经非常成熟。深部脑刺激(DBS)治疗严重的、难治性精神疾病目前正准备从经验主义阶段过渡到一个日益植根于科学发现的阶段。目前这种转变的驱动因素是神经影像学的进步,但迅速出现的是神经生理学——随着我们更多地了解这些疾病的神经基础,我们将能够更成功地使用干预措施,如侵入性刺激,来恢复功能失调的神经回路的健康。与这种转变并行的是结果数据的一致性和质量的稳步提高。在这里,我们关注强迫症和抑郁症,这两个主题在试验量和科学努力方面受到了最多的关注。
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引用次数: 4
期刊
Annual review of neuroscience
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