Current Opinion in Neurobiology最新文献

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Bridging the gap between physics and biology of hearing: Timing and amplification 弥合物理和听觉生物学之间的差距：时间和放大

IF 5.2 2区医学 Q1 NEUROSCIENCES

Current Opinion in Neurobiology

Pub Date : 2025-12-13 DOI: 10.1016/j.conb.2025.103148

Christine Petit , Paul Avan

In mammals, the exquisite sensitivity and frequency selectivity of sound analysis rests on properly timed cycle-by-cycle feedback that compensates for friction and tunes the mechanical resonances of the auditory sensory organ. This feedback must operate at the highest audible frequencies, more than 100 kHz in some species, a feat given that it relies upon voltage-driven conformation changes of a protein called prestin, which forms an array along the lateral membrane of outer hair cell endowing them with electromotility. In the first place, the voltage that actuates prestin results from mechanotransduction of sound-induced vibrations by a mechanosensitive protein complex hosted in hair cell microvilli called stereocilia, whose nanometric deflections must ensure ion channel activation within microseconds. Many molecular assemblies and configurations allowing mechanosensitive detection to be pushed to such physical scales in terms of displacement and time, a unique requirement of hearing among mechanosensory systems, are still under active investigations.

在哺乳动物中，声音分析的灵敏度和频率选择性依赖于适当的周期反馈，这种反馈补偿了摩擦，调节了听觉器官的机械共振。这种反馈必须在最高可听频率下运行，在某些物种中超过100千赫，这是一项壮举，因为它依赖于电压驱动的一种叫做prestin的蛋白质的构象变化，prestin沿着外毛细胞的外侧膜形成阵列，赋予它们电运动性。首先，驱动prestin的电压来自于毛细胞微绒毛（称为立体纤毛）中的机械敏感蛋白复合物对声音引起的振动的机械转导，其纳米级的偏转必须确保离子通道在微秒内被激活。许多分子组合和结构允许机械敏感检测在位移和时间方面被推到这样的物理尺度，这是机械感觉系统中听觉的独特要求，目前仍在积极研究中。

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Neural basis of sexually dimorphic decision-making 两性二态决策的神经基础。

IF 5.2 2区医学 Q1 NEUROSCIENCES

Current Opinion in Neurobiology

Pub Date : 2025-12-11 DOI: 10.1016/j.conb.2025.103146

Megan Day , Carolina Rezaval

Animals continually arbitrate between incompatible behaviors: whether to feed or flee, mate or fight, sleep or explore. The brain must select, suppress, and sequence actions according to sensory inputs, internal state, and likely success. Sexual dimorphism adds complexity: males and females face distinct reproductive pressures and often resolve conflicts in divergent ways. Yet the neural mechanisms underlying sex-specific prioritization remain poorly understood. Drosophila melanogaster offers a powerful model for dissecting action selection at cellular and circuit resolution. Here, we synthesize recent advances revealing how sexually dimorphic neurons act as integrator hubs, combining sensory cues with internal states to bias choice in both sexes. Neuromodulators confer flexibility, dynamically reweighting priorities as circumstances shift. Dopamine, in particular, filters distracting stimuli and tunes evidence accumulation, enabling priorities to update as goals approach. These studies outline emerging principles of action selection across contexts and sexes and suggest conserved strategies for balancing drives across species.

动物不断地在不相容的行为之间进行仲裁：是吃还是逃，是交配还是打架，是睡觉还是探索。大脑必须根据感官输入、内部状态和可能的成功来选择、抑制和排序动作。两性二态性增加了复杂性：男性和女性面临着不同的生殖压力，往往以不同的方式解决冲突。然而，基于性别的优先排序的神经机制仍然知之甚少。黑腹果蝇为在细胞和电路分辨率上解剖动作选择提供了一个强大的模型。在这里，我们综合了最近的研究进展，揭示了两性二态神经元如何作为整合中心，将感官线索与两性的内部状态结合起来，以进行偏见选择。神经调节剂赋予灵活性，随着环境的变化动态地调整优先级。尤其是多巴胺，它可以过滤分散注意力的刺激，调整证据积累，使优先级随着目标的临近而更新。这些研究概述了跨环境和性别的行为选择的新原则，并提出了跨物种平衡驱动的保守策略。

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Forward and backward prediction in learning and perception 学习和感知中的前向和后向预测。

IF 5.2 2区医学 Q1 NEUROSCIENCES

Current Opinion in Neurobiology

Pub Date : 2025-12-10 DOI: 10.1016/j.conb.2025.103144

Floris P. de Lange , Clare Press

Predictive processing frameworks have emphasized the role of forward prediction as a critical ingredient for learning and perceptual inference. We anticipate sensory events that are likely in the future on the basis of past and current sensory events. By comparing these forward predictions against incoming input, we can obtain an accurate estimate of the environment (i.e. perceive) and improve the predictions themselves (i.e. learn). Interestingly however, research in the field of statistical learning has taught us that backward predictive relationships - reflecting the probability of past events given present events - are learnt equally well. This questions the privileged status of forward-looking mechanisms. Here we discuss commonalities and differences between implications for learning and perception. We conclude that while forward and backward predictive relationships both shape learning, we retrieve future, but not past, predicted states during perception.

预测处理框架强调了前向预测作为学习和感知推理的关键成分的作用。我们在过去和现在的感觉事件的基础上预测未来可能发生的感觉事件。通过将这些前向预测与输入进行比较，我们可以获得对环境的准确估计（即感知）并改进预测本身（即学习）。然而，有趣的是，统计学习领域的研究告诉我们，反向预测关系——反映过去事件给定当前事件的概率——同样可以很好地学习。这对前瞻性机制的特权地位提出了质疑。在这里，我们讨论学习和感知暗示之间的共性和差异。我们的结论是，虽然向前和向后的预测关系都影响了学习，但我们在感知过程中获取的是未来而不是过去的预测状态。

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Hippocampal and cortical contributions to statistical learning 海马和皮质对统计学习的贡献。

IF 5.2 2区医学 Q1 NEUROSCIENCES

Current Opinion in Neurobiology

Pub Date : 2025-12-01 DOI: 10.1016/j.conb.2025.103136

Irene Zhou, Nicholas B. Turk-Browne

The human brain is adept at extracting regularities from our environment, allowing us to behave adaptively and make predictions. Research on the neural basis of this statistical learning has diverged in recent years based on the brain mechanism being investigated and the timing and modality of the regularities. One literature has focused on the entrainment of neural oscillations to rapid auditory sequences in cortical regions. The other literature has focused on changes in the similarity of neural representations for slower visual sequences in the hippocampus. By reuniting these literatures, we identify a potential role for the hippocampus in generalizing over temporal variability and suggest how hippocampal-cortical interactions could support statistical learning.

人类的大脑善于从我们的环境中提取规律，使我们能够自适应地行动并做出预测。近年来，基于所研究的脑机制以及规律的时间和形态，对这种统计学习的神经基础的研究出现了分歧。一篇文献聚焦于皮层区域快速听觉序列的神经振荡的携带。其他文献关注的是海马体中较慢视觉序列的神经表征相似性的变化。通过重新整合这些文献，我们确定了海马体在概括时间变异性方面的潜在作用，并提出了海马体-皮层相互作用如何支持统计学习。

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Mechanisms of proteostasis in neuronal development and plasticity 蛋白质在神经元发育和可塑性中的作用机制

IF 5.2 2区医学 Q1 NEUROSCIENCES

Current Opinion in Neurobiology

Pub Date : 2025-11-28 DOI: 10.1016/j.conb.2025.103143

Beatriz Maio , Francesca Aria , Susana R. Louros , Emily K. Osterweil

The careful regulation of the protein lifecycle is important for cellular function, particularly during times of change. In neurons, the specializations needed to maintain the steady-state proteome at multiple subcellular domains and respond rapidly to activity have brought about unique mechanisms in messenger RNA (mRNA) translation and protein degradation. Recent research continues to illuminate these critical mechanisms, giving us a deeper understanding of the nervous system and identifying new targets for the treatment of neurological disorders. In this review, we highlight the new research shedding light on the mechanisms of proteostasis in brain development and plasticity. These studies emphasize the extent to which protein synthesis and degradation participate in brain function and how disruptions of proteostasis lead to disorders of the nervous system.

仔细调节蛋白质的生命周期对细胞功能是重要的，特别是在变化时期。在神经元中，维持蛋白质组在多个亚细胞结构域的稳态和对活动的快速反应所需的特化带来了信使RNA （mRNA）翻译和蛋白质降解的独特机制。最近的研究继续阐明这些关键机制，使我们对神经系统有了更深入的了解，并确定了治疗神经系统疾病的新靶点。在本文中，我们重点介绍了蛋白质停滞在大脑发育和可塑性中的新研究。这些研究强调了蛋白质合成和降解参与脑功能的程度，以及蛋白质平衡的破坏如何导致神经系统紊乱。

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The genetics of autosomal recessive early-onset Parkinson's disease 常染色体隐性早发性帕金森病的遗传学研究。

IF 5.2 2区医学 Q1 NEUROSCIENCES

Current Opinion in Neurobiology

Pub Date : 2025-11-17 DOI: 10.1016/j.conb.2025.103141

Guillaume Cogan, Suzanne Lesage, Alexis Brice

Early-onset Parkinson's disease (EOPD) is usually defined as Parkinson's disease (PD) occurring before the age of 40–50 years. Unlike late-onset PD, EOPD is often due to pathogenic mutations in autosomal recessive genes. Two phenotypes can be distinguished: typical EOPD, which progresses slowly (PRKN, PINK1 and DJ-1), and atypical PD, often associated with additional symptoms (ATP13A2, FBXO7, DNAJC6, VPS13C, SYNJ1, PLA2G6). In this review, we will highlight recent advances and remaining challenges. The frequency of causal genetic mutations and the genotype-phenotype landscape of PRKN-associated PD has been refined. Long-read sequencing has solved several undiagnosed cases with a single PRKN mutation. Five new genes have been reported to contribute to EOPD associated with various neurological signs (PTPA, DAGLB, PSMF1, EPG5, SGIP1). Small molecules targeting PRKN dysfunctions are expected to enter clinical trials in the coming years, paving the way for targeted therapies in EOPD.

早发性帕金森病（EOPD）通常被定义为40-50岁之前发生的帕金森病（PD）。与迟发性帕金森病不同，EOPD通常是由常染色体隐性基因的致病突变引起的。可以区分两种表型：典型的EOPD，其进展缓慢（PRKN、PINK1和DJ-1），以及非典型PD，通常伴有其他症状（ATP13A2、FBXO7、DNAJC6、VPS13C、SYNJ1、PLA2G6）。在这篇综述中，我们将强调最近的进展和仍然存在的挑战。因果基因突变的频率和prkn相关PD的基因型-表型景观已被完善。长读测序已经解决了几个未确诊的单一PRKN突变病例。据报道，有5个新基因与EOPD相关，并伴有各种神经症状（PTPA、DAGLB、PSMF1、EPG5、SGIP1）。靶向PRKN功能障碍的小分子有望在未来几年进入临床试验，为EOPD的靶向治疗铺平道路。

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Corrigendum to “Single vesicle tracking for studying synaptic vesicle dynamics in small central synapses” [Curr Opin Neurobiol (76) (2022) 102596] “单个囊泡跟踪用于研究小中枢突触的突触囊泡动力学”的勘误表[当代神经生物学杂志（76）（2022）102596]。

IF 5.2 2区医学 Q1 NEUROSCIENCES

Current Opinion in Neurobiology

Pub Date : 2025-11-17 DOI: 10.1016/j.conb.2025.103142

Chungwon Park , Sangyong Jung , Hyokeun Park

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Protein mechanism and therapeutic design in Parkinson's disease: A structural biology perspective 帕金森病的蛋白质机制和治疗设计：结构生物学视角。

IF 5.2 2区医学 Q1 NEUROSCIENCES

Current Opinion in Neurobiology

Pub Date : 2025-11-16 DOI: 10.1016/j.conb.2025.103140

Danielle M. Simons , Jean-François Trempe

Parkinson's disease (PD) remains one of the most elusive, progressive neurological diseases to treat due to an incomplete understanding of its pathology. Current symptomatic therapies revolve around alleviating symptoms with dopamine replacement therapy; however, this mode of treatment does not always provide long-term relief or address the underlying cause. Thus, there is still a need to better understand the mechanisms of proteins implicated in neurodegeneration as the key to developing disease-modifying treatments. Here we discuss recent advances in our understanding of six protein targets for PD therapy: α-synuclein, LRRK2, GBA1, PARKIN, PINK1, and USP30. For each, we highlight novel structures that shine light both on pathogenic mechanisms as well as novel therapies. We discuss drugs targeting these proteins that are in clinical trials, and how structures are used to improve them.

帕金森氏病（PD）仍然是一个最难以捉摸的，进行性神经系统疾病治疗由于不完全了解其病理。目前的对症治疗围绕着用多巴胺替代疗法缓解症状；然而，这种治疗方式并不总是提供长期的缓解或解决根本原因。因此，仍有必要更好地了解与神经退行性变有关的蛋白质的机制，这是开发改善疾病治疗的关键。在这里，我们讨论了最近我们对PD治疗的六个蛋白靶点的理解进展：α-突触核蛋白，LRRK2, GBA1， PARKIN， PINK1和USP30。对于每一种，我们都强调了新的结构，这些结构既照亮了致病机制，也照亮了新的治疗方法。我们将讨论临床试验中针对这些蛋白质的药物，以及如何使用结构来改善它们。

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Setting the stage for statistical learning? Sensitivity to environmental statistics in early sensory processing 为统计学学习搭建舞台？早期感觉加工中对环境统计的敏感性。

IF 5.2 2区医学 Q1 NEUROSCIENCES

Current Opinion in Neurobiology

Pub Date : 2025-11-15 DOI: 10.1016/j.conb.2025.103139

Miguel Maravall , Livia de Hoz

Our brains make sense of the world on a moment-by-moment basis despite its enormous complexity, largely because its overall statistical structure can be detected, learned, and generalized across experiences. Exposure to specific regularities (e.g., in speech) results in an unsupervised, incidental, form of learning, commonly known as statistical learning (SL). SL is well-established from a cognitive perspective and often assumed to require high-level cortical or hippocampal processing. However, accumulating evidence suggests that SL emerges much earlier in ascending sensory pathways. Despite this, our understanding of the forms it might take in subcortical sensory centres is relatively limited. Here, we review neuronal sensitivity to statistics in early sensory regions and ask how this sensitivity relates to SL. We feature examples of adaptive responses elicited by stimulus repetitions, omissions, changes in stimulus distribution, and more complex patterning, highlighting the interplay between adaptive coding and SL as manifestations of sensitivity to environmental statistics.

我们的大脑在每时每刻的基础上理解世界，尽管它非常复杂，很大程度上是因为它的整体统计结构可以通过经验被检测、学习和概括。暴露于特定的规律（例如，在讲话中）会导致一种无监督的、偶然的学习形式，通常被称为统计学习（SL）。从认知的角度来看，SL是公认的，通常认为它需要高水平的皮层或海马处理。然而，越来越多的证据表明，SL在上升感觉通路中出现得更早。尽管如此，我们对它在皮层下感觉中心可能采取的形式的理解相对有限。在这里，我们回顾了早期感觉区域的神经元对统计数据的敏感性，并询问这种敏感性与SL之间的关系。我们以刺激重复、省略、刺激分布变化和更复杂的模式引起的适应性反应为例，强调了适应性编码和SL之间的相互作用，作为对环境统计敏感性的表现。

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From neurons to novelty: Circuit mechanisms shaping courtship evolution 从神经元到新奇：形成求爱进化的电路机制

IF 5.2 2区医学 Q1 NEUROSCIENCES

Current Opinion in Neurobiology

Pub Date : 2025-11-15 DOI: 10.1016/j.conb.2025.103137

Philipp Brand , Rory T. Coleman

The vast diversity of animal behaviors has long inspired ethologists and neuroscientists, but circuit mechanisms driving this variation remain elusive. Recent advances in genetic tools and comparative approaches have enabled unprecedented insights into how neural circuits evolve to produce behavioral novelty. Here we focus on the discoveries emerging from the study of courtship behaviors, which are particularly well poised to capitalize on these advances. Comparative studies of sensory and motor circuits have begun to demonstrate that evolution can act through diverse mechanisms. The modular organization of courtship-controlling circuits emerges as a key feature facilitating rapid evolutionary innovation while maintaining essential functions. Changes in the neuronal composition of circuits, by both cellular and subcellular mechanisms, represent common mechanisms. Organisms may even carry vestigial circuits with the latent potential to be repurposed for new behavioral paradigms. We highlight how understanding the ‘extended nervous system’ of a species has begun to provide these critical insights into courtship evolution and offers fertile ground for future discoveries. As comparative approaches expand beyond model organisms, evolutionary neuroscience is on the cusp of revealing the principles governing behavioral diversity in nature.

动物行为的巨大多样性长期以来一直激励着行为学家和神经科学家，但驱动这种变化的电路机制仍然难以捉摸。遗传工具和比较方法的最新进展使我们能够前所未有地深入了解神经回路是如何进化产生新奇行为的。在这里，我们将重点关注从求偶行为研究中出现的发现，这些发现特别适合利用这些进步。对感觉回路和运动回路的比较研究已经开始表明，进化可以通过多种机制起作用。求爱控制电路的模块化组织成为促进快速进化创新的关键特征，同时保持基本功能。通过细胞和亚细胞机制，神经元回路组成的变化代表了共同的机制。生物体甚至可能携带有潜在潜力的退化回路，以重新利用新的行为范式。我们强调如何理解一个物种的“扩展神经系统”已经开始为求爱进化提供这些关键的见解，并为未来的发现提供肥沃的土壤。随着比较方法扩展到模式生物之外，进化神经科学正处于揭示自然界行为多样性支配原则的尖端。

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