Current Opinion in Neurobiology最新文献

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The convoluted path leading to neuronal circuit formation 导致神经元回路形成的迂回路径。

IF 4.8 2区医学 Q1 NEUROSCIENCES

Current Opinion in Neurobiology

Pub Date : 2025-02-01 DOI: 10.1016/j.conb.2024.102941

Carla G. Silva

A limiting step of neuronal circuit formation is the extensive migration of interneurons from their birthplace to populate territories formed by excitatory neurons. Interneuron dynamics in the developing brain culminates with the organization of interneuron subtypes in specific configurations within layers of brain tissue. Decoding the logic behind these configurations is still matter of passionate debate. Do interneurons follow a sketched program from the progenitor state or is this organization sculpted from intricate cellular interactions? How do interneurons select interacting partners? How does interneuron diversity emerge? New technologies and access to brain tissue from different species are allowing us to reconstruct stone by stone, the convoluted path leading to the formation of neuronal cell assemblies made of excitatory and inhibitory neurons. The most recent research highlights that interneuron subtype circuit integration needs to be assessed case by case. Here, I highlight the need to keep delving into the complexities of interneuron interaction with their environment during development to accomplish this Herculean task.

神经元回路形成的一个限制步骤是中间神经元从它们的出生地大量迁移到由兴奋性神经元形成的区域。发育中的大脑中的中间神经元动力学在脑组织层内特定配置的中间神经元亚型的组织中达到高潮。解码这些配置背后的逻辑仍然是一个激烈辩论的问题。中间神经元是遵循祖细胞状态的一个草图程序，还是这个组织是从复杂的细胞相互作用中雕刻出来的？中间神经元是如何选择相互作用的伙伴的？中间神经元多样性是如何产生的？新技术和获取不同物种脑组织的途径使我们能够一块石头一块石头地重建，这条曲折的路径通向由兴奋性和抑制性神经元组成的神经元细胞组合的形成。最近的研究强调，中间神经元亚型电路的整合需要逐个评估。在这里，我强调有必要继续深入研究中间神经元在发育过程中与其环境相互作用的复杂性，以完成这项艰巨的任务。

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Phase separation in the multi-compartment organization of synapses

IF 4.8 2区医学 Q1 NEUROSCIENCES

Current Opinion in Neurobiology

Pub Date : 2025-02-01 DOI: 10.1016/j.conb.2025.102975

Shihan Zhu , Zeyu Shen , Xiandeng Wu , Mingjie Zhang

A neuronal synapse is formed by juxtaposition of a transmitter releasing presynaptic bouton of one neuron with a transmitter receiving postsynaptic compartment such as a spine protrusion of another neuron. Each presynaptic bouton and postsynaptic spine, though very small in their volumes already, are further compartmentalized to micro-/nano-domains with distinct molecular organizations and synaptic functions. This review summarizes studies in recent years demonstrating that multivalent protein–protein interaction-induced phase separation underlies formation and coexistence of multiple distinct molecular condensates within tiny synapses. In post-synapses where synaptic compartmentalization via phase separation was first demonstrated, phase separation allows clustering of transmitter receptors into distinct nanodomains and renders postsynaptic densities to be regulated by synaptic stimulation signals for plasticity. In pre-synapses, such phase separation-mediated synaptic condensates formation allows SVs to be stored as distinct pools and directly transported for activity-induced transmitter release.

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Signaling in autism: Relevance to nutrients and sex 自闭症中的信号：与营养和性有关。

IF 4.8 2区医学 Q1 NEUROSCIENCES

Current Opinion in Neurobiology

Pub Date : 2025-02-01 DOI: 10.1016/j.conb.2024.102962

Yi-Ping Hsueh

Autism spectrum disorders (ASD) are substantially heterogeneous neuropsychiatric conditions with over a thousand associated genetic factors and various environmental influences, such as infection and nutrition. Additionally, males are four times more likely than females to be affected. This heterogeneity underscores the need to uncover common molecular features within ASD. Recent studies have revealed interactions among genetic predispositions, environmental factors, and sex that may be critical to ASD etiology. This review focuses on emerging evidence for the impact of nutrients—particularly zinc and amino acids—on ASD, as demonstrated in mouse models and human studies. These nutrients have been shown to influence synaptic signaling, dendritic spine formation, and behaviors linked to autism. Furthermore, sex-based differences in nutritional requirements, especially for zinc and amino acids, may contribute to the observed male bias in autism, indicating that interactions between nutrients and genetic factors could be integral to understanding and potentially mitigating ASD symptoms.

自闭症谱系障碍（ASD）本质上是一种异质性的神经精神疾病，有一千多种相关的遗传因素和各种环境影响，如感染和营养。此外，男性受影响的可能性是女性的四倍。这种异质性强调了发现ASD共同分子特征的必要性。最近的研究表明，遗传易感性、环境因素和性别之间的相互作用可能对ASD的病因至关重要。这篇综述的重点是在小鼠模型和人类研究中发现的营养素，特别是锌和氨基酸对ASD影响的新证据。这些营养物质已被证明可以影响突触信号、树突棘的形成以及与自闭症有关的行为。此外，基于性别的营养需求差异，特别是对锌和氨基酸的需求差异，可能会导致自闭症中观察到的男性偏见，这表明营养和遗传因素之间的相互作用可能是理解和潜在减轻ASD症状的组成部分。

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Bridging the fields of cognition and birdsong with corvids 用鸦类架起认知和鸟鸣领域的桥梁。

IF 4.8 2区医学 Q1 NEUROSCIENCES

Current Opinion in Neurobiology

Pub Date : 2025-02-01 DOI: 10.1016/j.conb.2024.102965

Diana A. Liao, Felix W. Moll, Andreas Nieder

Corvids, readily adaptable across social and ecological contexts, successfully inhabit almost the entire world. They are seen as highly intelligent birds, and current research examines their cognitive abilities. Despite being songbirds with a complete ‘song system’, corvids have historically received less attention in studies of song production, learning, and perception compared to non-corvid songbirds. However, recent neurobiological studies have demonstrated that songbird vocal production and its neuronal representations are regularly influenced by environmental and cognitive factors. This opinion article discusses the literature on ‘corvid song’ before introducing other flexible vocal behaviors of corvids in both the wild and controlled laboratory studies. We suggest corvids with their flexible vocal control as promising model species to study the links between brain networks for cognition and vocalization. Studying corvid vocal flexibility and associated cognitive processes in both ecological and lab settings offers complementary insights, crucial for bridging the fields of cognition and birdsong.

鸦科动物很容易适应各种社会和生态环境，几乎成功地栖息在整个世界。它们被认为是高智商的鸟类，目前的研究考察了它们的认知能力。尽管鸦科鸣禽拥有完整的“鸣叫系统”，但与非鸦科鸣禽相比，鸦科鸣禽在鸣叫、学习和感知方面的研究历来受到的关注较少。然而，最近的神经生物学研究表明，鸣禽的声音产生及其神经元表征经常受到环境和认知因素的影响。这篇观点文章在介绍野外和受控实验室研究中鸦科动物的其他灵活发声行为之前，讨论了关于鸦科动物之歌的文献。我们建议鸦具有灵活的声音控制能力，作为研究认知和发声大脑网络之间联系的有希望的模型物种。在生态和实验室环境中研究鸦的声音灵活性和相关的认知过程提供了互补的见解，对于连接认知和鸟鸣领域至关重要。

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Neurobiological mechanisms of forgetting across timescales

IF 4.8 2区医学 Q1 NEUROSCIENCES

Current Opinion in Neurobiology

Pub Date : 2025-02-01 DOI: 10.1016/j.conb.2025.102972

Mitchell L. de Snoo , Paul W. Frankland

Every species in the animal kingdom that learns, also forgets. Despite this balance between learning and forgetting, most neuroscientific explorations of memory have focused on how learning occurs, with recent studies identifying engrams as putative biological substrates for memory. Here we review an emerging literature that, in contrast, explores how our brains forget. These studies reveal that forgetting engages a broad collection of mechanisms that function to reduce engram accessibility. However, changes in accessibility emerge on vastly different timescales. At short timescales, forgetting is modulated by fluctuations in brain states that alter engram accessibility in a moment-to-moment fashion. In the intermediate- and long-term, forgetting depends, in part, on mechanisms that rewire engrams, rendering them gradually harder to access. Viewed this way, forgetting encompasses a family of plasticity mechanisms that modulate engram accessibility, perhaps in order to prioritize those memories that are most timely or relevant to the situation at hand.

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Animal models of the human brain: Successes, limitations, and alternatives

IF 4.8 2区医学 Q1 NEUROSCIENCES

Current Opinion in Neurobiology

Pub Date : 2025-02-01 DOI: 10.1016/j.conb.2024.102969

Nancy Kanwisher

The last three decades of research in human cognitive neuroscience have given us an initial “parts list” for the human mind in the form of a set of cortical regions with distinct and often very specific functions. But current neuroscientific methods in humans have limited ability to reveal exactly what these regions represent and compute, the causal role of each in behavior, and the interactions among regions that produce real-world cognition. Animal models can help to answer these questions when homologues exist in other species, like the face system in macaques. When homologues do not exist in animals, for example for speech and music perception, and understanding of language or other people's thoughts, intracranial recordings in humans play a central role, along with a new alternative to animal models: artificial neural networks.

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Genetic advances and translational phenotypes in rodent models for Tourette disorder 图雷特病啮齿动物模型的遗传进展和翻译表型。

IF 4.8 2区医学 Q1 NEUROSCIENCES

Current Opinion in Neurobiology

Pub Date : 2025-02-01 DOI: 10.1016/j.conb.2024.102967

Tess F. Kowalski , Riley Wang , Max A. Tischfield

Tourette disorder (TD) is a neurodevelopmental condition affecting approximately 0.3%–1% of children and adolescents. It is defined by motor and vocal tics but encompasses wide ranging phenotypes due to its complex genetic origins, involving hundreds of risk genes across various signaling pathways. Traditional animal models of TD have focused on circuit manipulation or neuron ablation strategies to investigate its underlying causes and associated brain changes. However, the recent identification of high-confidence risk genes has opened new possibilities for creating models that express the exact genetic variants associated with TD. This review discusses early attempts to model TD in rodents and highlights advancements in next-generation models with true construct validity through the expression of orthologous human mutations in high-confidence risk genes. Additionally, we examine the translational potential of integrating cognitive and sensorimotor approaches to evaluate TD-related phenotypes in rodents, including changes to reinforcement learning, habitual behavior, and incentive motivation.

抽动秽语症（TD）是一种影响大约0.3%-1%儿童和青少年的神经发育疾病。它是由运动和声音抽搐定义的，但由于其复杂的遗传起源，包括广泛的表型，涉及各种信号通路中的数百个风险基因。传统的动物模型主要集中在电路操作或神经元消融策略上，以研究其潜在原因和相关的大脑变化。然而，最近对高可信度风险基因的鉴定为创建表达与TD相关的确切遗传变异的模型提供了新的可能性。这篇综述讨论了在啮齿类动物中建立TD模型的早期尝试，并强调了通过在高置信度风险基因中表达同源人类突变来建立真正结构效度的下一代模型的进展。此外，我们研究了整合认知和感觉运动方法的转化潜力，以评估啮齿动物中td相关的表型，包括强化学习，习惯行为和激励动机的变化。

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引用次数: 0

Common alterations to astrocytes across neurodegenerative disorders

IF 4.8 2区医学 Q1 NEUROSCIENCES

Current Opinion in Neurobiology

Pub Date : 2025-02-01 DOI: 10.1016/j.conb.2025.102970

Aksinya Derevyanko , Tao Tao , Nicola J. Allen

Astrocytes perform multiple functions in the nervous system, many of which are altered in neurodegenerative disorders. In this review, we explore shared astrocytic alterations across neurodegenerative disorders, including Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and frontotemporal lobe degeneration. Assessing recent datasets of single-nucleus RNA-sequencing of human brains, a theme emerges of common alterations in astrocyte state across disorders including in neuroinflammation, synaptic organization, metabolic support, and the cellular stress response. Immune pathways are upregulated by astrocytes across disorders and may exacerbate neurodegeneration. Dysregulated expression of synaptogenic factors could contribute to synaptic loss, while compromised metabolic support affects neuronal homeostasis. On the other hand, upregulated responses to cellular stress may represent a protective response of astrocytes and thus mitigate pathology. Understanding these shared responses offers insights into disease progression and provides potential therapeutic targets for various neurodegenerative disorders.

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New insights into the molecular architecture of neurons by cryo-electron tomography 通过低温电子断层扫描对神经元分子结构的新见解。

IF 4.8 2区医学 Q1 NEUROSCIENCES

Current Opinion in Neurobiology

Pub Date : 2025-02-01 DOI: 10.1016/j.conb.2024.102939

Arsen Petrovic , Thanh Thao Do , Rubén Fernández-Busnadiego

Cryo-electron tomography (cryo-ET) visualizes natively preserved cellular ultrastructure at molecular resolution. Recent developments in sample preparation workflows and image processing tools enable growing applications of cryo-ET in cellular neurobiology. As such, cryo-ET is beginning to unravel the in situ macromolecular organization of neurons using samples of increasing complexity. Here, we highlight advances in cryo-ET technology and review its recent use to study neuronal architecture and its alterations under disease conditions.

低温电子断层扫描（cryo-ET）以分子分辨率显示原生保存的细胞超微结构。样品制备工作流程和图像处理工具的最新发展使cryo-ET在细胞神经生物学中的应用越来越广泛。因此，cryo-ET开始使用越来越复杂的样品来解开神经元的原位大分子组织。在这里，我们重点介绍了冷冻et技术的进展，并回顾了其最近在研究疾病条件下神经元结构及其变化方面的应用。

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Turning garbage into gold: Autophagy in synaptic function 变废为宝突触功能中的自噬作用

IF 4.8 2区医学 Q1 NEUROSCIENCES

Current Opinion in Neurobiology

Pub Date : 2025-02-01 DOI: 10.1016/j.conb.2024.102937

Erin Marie Smith , Maeve Louise Coughlan , Sandra Maday

Trillions of synapses in the human brain enable thought and behavior. Synaptic connections must be established and maintained, while retaining dynamic flexibility to respond to experiences. These processes require active remodeling of the synapse to control the composition and integrity of proteins and organelles. Macroautophagy (hereafter, autophagy) provides a mechanism to edit and prune the synaptic proteome. Canonically, autophagy has been viewed as a homeostatic process, which eliminates aged and damaged proteins to maintain neuronal survival. However, accumulating evidence suggests that autophagy also degrades specific cargoes in response to neuronal activity to impact neuronal transmission, excitability, and synaptic plasticity. Here, we will discuss the diverse roles, regulation, and mechanisms of neuronal autophagy in synaptic function and contributions from glial autophagy in these processes.

人类大脑中数以万亿计的突触使我们能够思考和行为。突触连接必须建立和维持，同时保持对经验的动态灵活性。这些过程需要突触的主动重塑来控制蛋白质和细胞器的组成和完整性。巨噬（Macroautophagy，以下简称自噬）提供了一种编辑和修剪突触蛋白质组的机制。通常，自噬被认为是一个自我平衡的过程，它消除老化和受损的蛋白质来维持神经元的存活。然而，越来越多的证据表明，自噬也会降解特定的货物，以响应神经元的活动，从而影响神经元的传递、兴奋性和突触可塑性。在这里，我们将讨论神经元自噬在突触功能中的各种作用、调节和机制，以及胶质自噬在这些过程中的贡献。

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