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Augustus Waller’s foresight realized: SARM1 in peripheral neuropathies 奥古斯都-沃勒的远见卓识得以实现:SARM1 在周围神经病中的应用
IF 5.7 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-06-08 DOI: 10.1016/j.conb.2024.102884
Stefanie Geisler

Peripheral neuropathy is a common neurodegenerative condition characterized by numbness, tingling, pain, and weakness that frequently starts in the distal limbs. Arising from multiple etiologies, many peripheral neuropathies exhibit a slowly progressive course due to axon degeneration for which no effective treatments exist. During the past decade, numerous crucial insights into mechanisms of axon degeneration in peripheral neuropathies emerged from experiments involving nerve-cutting procedures, revealing the central role of the SARM1 axon degeneration pathway in both. Here I review commonalities and differences in the role of SARM1 after nerve cut and in several acquired and inherited peripheral neuropathies. This new knowledge now paves the way for the development of therapeutics that directly address root causes of various kinds of neuropathies.

周围神经病变是一种常见的神经退行性疾病,以麻木、刺痛、疼痛和无力为特征,多发于四肢远端。许多周围神经病由多种病因引起,因轴突变性而呈现缓慢进展的过程,目前尚无有效的治疗方法。过去十年间,通过神经切割实验,人们对周围神经病轴突变性的机制有了许多重要的认识,揭示了 SARM1 轴突变性途径在这两种疾病中的核心作用。在此,我回顾了神经切断后 SARM1 在几种获得性和遗传性周围神经病中作用的共性和差异。这些新知识为开发直接解决各种神经病变根本原因的疗法铺平了道路。
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引用次数: 0
Understanding collective behavior through neurobiology 通过神经生物学了解集体行为
IF 5.7 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-06-01 DOI: 10.1016/j.conb.2024.102866
Jo-Hsien Yu , Julia L. Napoli , Matthew Lovett-Barron

A variety of organisms exhibit collective movement, including schooling fish and flocking birds, where coordinated behavior emerges from the interactions between group members. Despite the prevalence of collective movement in nature, little is known about the neural mechanisms producing each individual's behavior within the group. Here we discuss how a neurobiological approach can enrich our understanding of collective behavior by determining the mechanisms by which individuals interact. We provide examples of sensory systems for social communication during collective movement, highlight recent discoveries about neural systems for detecting the position and actions of social partners, and discuss opportunities for future research. Understanding the neurobiology of collective behavior can provide insight into how nervous systems function in a dynamic social world.

许多生物都表现出集体运动的特征,包括成群的鱼类和鸟类,群体成员之间的相互作用会产生协调的行为。尽管集体运动在自然界十分普遍,但人们对群体中每个个体行为的神经机制却知之甚少。在此,我们将讨论神经生物学方法如何通过确定个体之间的互动机制来丰富我们对集体行为的理解。我们将举例说明集体运动过程中用于社会交流的感官系统,重点介绍最近发现的用于检测社会伙伴位置和行动的神经系统,并讨论未来的研究机会。了解集体行为的神经生物学可以让我们深入了解神经系统如何在动态的社会世界中发挥作用。
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引用次数: 0
Refining the circuits of drug addiction: The ventral pallidum 完善吸毒成瘾的回路:腹侧苍白球
IF 5.7 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-05-29 DOI: 10.1016/j.conb.2024.102883
Gessynger Morais-Silva , Mary Kay Lobo

The ventral pallidum is a prominent structure within the basal ganglia, regulating reward and motivational processes. Positioned at the interface between motor and limbic structures, its function is crucial to the development and maintenance of substance use disorders. Chronic drug use induces neuroplastic events in this structure, leading to long-term changes in VP neuronal activity and synaptic communication. Moreover, different neuronal populations within the VP drive drug-seeking behavior in opposite directions. This review explores the role of the VP as a hub for reward, motivation, and aversion, establishing it as an important contributor to the pathophysiology of substance use disorders.

腹侧苍白球是基底神经节内的一个重要结构,负责调节奖赏和动机过程。它位于运动和边缘结构的交界处,其功能对药物使用障碍的发展和维持至关重要。长期使用药物会诱发该结构的神经可塑性事件,导致VP神经元活动和突触通信发生长期变化。此外,VP 内不同的神经元群会以相反的方向驱动寻求毒品的行为。这篇综述探讨了VP作为奖赏、动机和厌恶中心的作用,将其确立为药物使用障碍病理生理学的一个重要因素。
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引用次数: 0
Natural visual behavior and active sensing in the mouse 小鼠的自然视觉行为和主动感应
IF 5.7 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-05-04 DOI: 10.1016/j.conb.2024.102882
Rolf J. Skyberg, Cristopher M. Niell

In the natural world, animals use vision for a wide variety of behaviors not reflected in most laboratory paradigms. Although mice have low-acuity vision, they use their vision for many natural behaviors, including predator avoidance, prey capture, and navigation. They also perform active sensing, moving their head and eyes to achieve behavioral goals and acquire visual information. These aspects of natural vision result in visual inputs and corresponding behavioral outputs that are outside the range of conventional vision studies but are essential aspects of visual function. Here, we review recent studies in mice that have tapped into natural behavior and active sensing to reveal the computational logic of neural circuits for vision.

在自然界中,动物利用视觉进行各种各样的行为,这在大多数实验室范例中都没有反映出来。虽然小鼠的视觉清晰度较低,但它们在许多自然行为中都会使用视觉,包括躲避捕食者、捕捉猎物和导航。它们还进行主动感知,移动头部和眼睛以实现行为目标并获取视觉信息。自然视觉的这些方面会产生视觉输入和相应的行为输出,这超出了传统视觉研究的范围,但却是视觉功能的重要方面。在此,我们回顾了最近对小鼠进行的研究,这些研究利用自然行为和主动感知来揭示视觉神经回路的计算逻辑。
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引用次数: 0
Studying dominance and aggression requires ethologically relevant paradigms 研究支配力和攻击性需要与伦理学相关的范例
IF 5.7 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-05-01 DOI: 10.1016/j.conb.2024.102879
Yair Shemesh , Asaf Benjamin , Keren Shoshani-Haye , Ofer Yizhar , Alon Chen

Although aggression is associated with several psychiatric disorders, there is no effective treatment nor a rigorous definition for “pathological aggression”. Mice make a valuable model for studying aggression. They have a dynamic social structure that depends on the habitat and includes reciprocal interactions between the mice's aggression levels, social dominance hierarchy (SDH), and resource allocation. Nevertheless, the classical behavioral tests for territorial aggression and SDH in mice are reductive and have limited ethological and translational relevance. Recent work has explored the use of semi-natural environments to simultaneously study dominance-related behaviors, resource allocation, and aggressive behavior. Semi-natural setups allow experimental control of the environment combined with manipulations of neural activity. We argue that these setups can help bridge the translational gap in aggression research toward discovering neuronal mechanisms underlying maladaptive aggression.

虽然攻击行为与多种精神疾病有关,但目前还没有有效的治疗方法,也没有对 "病理性攻击行为 "进行严格的定义。小鼠是研究攻击行为的重要模型。小鼠具有动态的社会结构,这种结构取决于栖息地,包括小鼠的攻击水平、社会支配等级(SDH)和资源分配之间的相互影响。然而,对小鼠领地攻击性和社会支配等级的经典行为测试是还原性的,在伦理学和转化方面的意义有限。最近的研究探索了利用半自然环境同时研究支配相关行为、资源分配和攻击行为的方法。半自然环境允许对环境进行实验控制,同时对神经活动进行操作。我们认为,这些设置有助于缩小攻击研究的转化差距,从而发现不良攻击行为背后的神经元机制。
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引用次数: 0
Ethological computational psychiatry: Challenges and opportunities 伦理计算精神病学:挑战与机遇
IF 5.7 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-05-01 DOI: 10.1016/j.conb.2024.102881
Ilya E. Monosov , Jan Zimmermann , Michael J. Frank , Mackenzie W. Mathis , Justin T. Baker

Studying the intricacies of individual subjects' moods and cognitive processing over extended periods of time presents a formidable challenge in medicine. While much of systems neuroscience appropriately focuses on the link between neural circuit functions and well-constrained behaviors over short timescales (e.g., trials, hours), many mental health conditions involve complex interactions of mood and cognition that are non-stationary across behavioral contexts and evolve over extended timescales. Here, we discuss opportunities, challenges, and possible future directions in computational psychiatry to quantify non-stationary continuously monitored behaviors. We suggest that this exploratory effort may contribute to a more precision-based approach to treating mental disorders and facilitate a more robust reverse translation across animal species. We conclude with ethical considerations for any field that aims to bridge artificial intelligence and patient monitoring.

在医学领域,长时间研究受试者的复杂情绪和认知处理过程是一项艰巨的挑战。系统神经科学的大部分研究都集中在神经回路功能与短时标(如试验、数小时)内约束良好的行为之间的联系上,而许多精神健康状况都涉及情绪与认知的复杂互动,这种互动在不同行为背景下是非稳态的,并在较长的时间尺度内不断演变。在此,我们将讨论计算精神病学在量化非稳态连续监测行为方面的机遇、挑战和未来可能的发展方向。我们认为,这种探索性的努力可能有助于以更精确的方法治疗精神障碍,并促进动物物种间更有力的反向转化。最后,我们将对任何旨在连接人工智能和患者监控的领域提出伦理方面的考虑。
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引用次数: 0
A conserved brainstem region for instinctive behaviour control: The vertebrate periaqueductal gray 控制本能行为的脑干保守区域脊椎动物的脊髓周围灰质
IF 5.7 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-04-24 DOI: 10.1016/j.conb.2024.102878
Anna Vanessa Stempel

Instinctive behaviours have evolved across animal phyla and ensure the survival of both the individual and species. They include behaviours that achieve defence, feeding, aggression, sexual reproduction, or parental care. Within the vertebrate subphylum, the brain circuits that support instinctive behaviour output are evolutionarily conserved, being present in the oldest group of living vertebrates, the lamprey. Here, I will provide an evolutionary and comparative perspective on the function of a conserved brainstem region central to the initiation and execution of virtually all instinctive behaviours—the periaqueductal gray. In particular, I will focus on recent advances on the neural mechanisms in the periaqueductal gray that underlie the production of different instinctive behaviours within and across species.

本能行为在各动物门类中不断进化,确保了个体和物种的生存。本能行为包括防御、进食、攻击、有性生殖或照顾父母等行为。在脊椎动物亚门中,支持本能行为输出的大脑回路在进化过程中得到了保留,存在于最古老的脊椎动物群体--鳗鱼中。在这里,我将从进化和比较的角度,介绍对几乎所有本能行为的启动和执行起核心作用的脑干保守区域--咽周灰质的功能。特别是,我将重点介绍最近在研究咽周灰神经机制方面取得的进展,这些机制是物种内部和物种之间产生不同本能行为的基础。
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引用次数: 0
Cognitive maps and the magnetic sense in vertebrates 脊椎动物的认知图谱和磁感
IF 5.7 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-04-23 DOI: 10.1016/j.conb.2024.102880
Runita N. Shirdhankar , E. Pascal Malkemper

Navigation requires a network of neurons processing inputs from internally generated cues and external landmarks. Most studies on the neuronal basis of navigation in vertebrates have focused on rats and mice and the canonical senses vision, hearing, olfaction, and somatosensation. Some animals have evolved the ability to sense the Earth's magnetic field and use it for orientation. It can be expected that in these animals magnetic cues are integrated with other sensory cues in the cognitive map. We provide an overview of the behavioral evidence and brain regions involved in magnetic sensing in support of this idea, hoping that this will guide future experiments.

导航需要神经元网络处理来自内部生成的线索和外部地标的输入。大多数关于脊椎动物导航神经元基础的研究都集中在大鼠和小鼠以及视觉、听觉、嗅觉和躯体感觉等典型感官上。有些动物进化出了感知地球磁场并利用磁场定向的能力。可以预见,在这些动物的认知图谱中,磁场线索与其他感官线索融为一体。我们概述了支持这一观点的行为证据和磁感应所涉及的大脑区域,希望这能为未来的实验提供指导。
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引用次数: 0
Dynamic skin behaviors in cephalopods 头足类动物的动态皮肤行为
IF 5.7 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-04-22 DOI: 10.1016/j.conb.2024.102876
Erica N. Shook , George Thomas Barlow , Daniella Garcia-Rosales , Connor J. Gibbons , Tessa G. Montague

The coleoid cephalopods (cuttlefish, octopus, and squid) are a group of soft-bodied mollusks that exhibit a wealth of complex behaviors, including dynamic camouflage, object mimicry, skin-based visual communication, and dynamic body patterns during sleep. Many of these behaviors are visually driven and engage the animals’ color changing skin, a pixelated display that is directly controlled by neurons projecting from the brain. Thus, cephalopod skin provides a direct readout of neural activity in the brain. During camouflage, cephalopods recreate on their skin an approximation of what they see, providing a window into perceptual processes in the brain. Additionally, cephalopods communicate their internal state during social encounters using innate skin patterns, and create waves of pigmentation on their skin during periods of arousal. Thus, by leveraging the visual displays of cephalopods, we can gain insight into how the external world is represented in the brain and how this representation is transformed into a recapitulation of the world on the skin. Here, we describe the rich skin behaviors of the coleoid cephalopods, what is known about cephalopod neuroanatomy, and how advancements in gene editing, machine learning, optical imaging, and electrophysiological tools may provide an opportunity to explore the neural bases of these fascinating behaviors.

鞘状头足类动物(墨鱼、章鱼和乌贼)是一类软体软体动物,它们表现出大量复杂的行为,包括动态伪装、物体模仿、基于皮肤的视觉交流以及睡眠时的动态身体模式。其中许多行为都是由视觉驱动的,动物的皮肤会变色,这种像素化的显示直接受大脑神经元投射的控制。因此,头足类的皮肤可以直接读出大脑神经活动。在伪装过程中,头足类动物会在皮肤上再现它们所看到的近似景象,这为了解大脑的感知过程提供了一个窗口。此外,头足类动物在社交活动中还会利用与生俱来的皮肤图案来传达自己的内心状态,并在兴奋期在皮肤上形成色素波。因此,通过利用头足类动物的视觉显示,我们可以深入了解外部世界如何在大脑中呈现,以及这种呈现如何转化为皮肤上世界的再现。在此,我们将描述头足类丰富的皮肤行为、对头足类神经解剖学的了解,以及基因编辑、机器学习、光学成像和电生理工具的进步如何为探索这些迷人行为的神经基础提供机会。
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引用次数: 0
Microglia phagocytic mechanisms: Development informing disease 小胶质细胞吞噬机制:发育为疾病提供信息
IF 5.7 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-04-16 DOI: 10.1016/j.conb.2024.102877
Rebecca M. Beiter , Patrick W. Sheehan , Dorothy P. Schafer

Microglia are tissue-resident macrophages and professional phagocytes of the central nervous system (CNS). In development, microglia-mediated phagocytosis is important for sculpting the cellular architecture. This includes the engulfment of dead/dying cells, pruning extranumerary synapses and axons, and phagocytosing fragments of myelin sheaths. Intriguingly, these developmental phagocytic mechanisms by which microglia sculpt the CNS are now appreciated as important for eliminating synapses, myelin, and proteins during neurodegeneration. Here, we discuss parallels between neurodevelopment and neurodegeneration, which highlights how development is informing disease. We further discuss recent advances and challenges towards therapeutically targeting these phagocytic pathways and how we can leverage development to overcome these challenges.

小胶质细胞是组织驻留巨噬细胞,也是中枢神经系统(CNS)的专业吞噬细胞。在发育过程中,小胶质细胞介导的吞噬作用对细胞结构的形成非常重要。这包括吞噬死亡/萎缩的细胞、修剪数量外的突触和轴突以及吞噬髓鞘碎片。耐人寻味的是,小胶质细胞对中枢神经系统进行雕刻的这些发育吞噬机制现在被认为是神经变性过程中消除突触、髓鞘和蛋白质的重要机制。在此,我们讨论了神经发育和神经变性之间的相似之处,这突出了发育如何为疾病提供信息。我们还将进一步讨论以这些吞噬途径为治疗目标的最新进展和挑战,以及我们如何利用发育克服这些挑战。
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引用次数: 0
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Current Opinion in Neurobiology
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