Nature Reviews Neuroscience最新文献_第3页

Using human 3D organoid models to gain mechanistic insight in motor neuron diseases 利用人体三维类器官模型获得运动神经元疾病的机制洞察。

IF 29 1区医学

Nature Reviews Neuroscience Pub Date : 2026-07-06 DOI: 10.1038/s41583-026-01057-x

Benedetta Frizzi, Adriana Margarida Barbosa Correia, Irene Faravelli, Ludo Van Den Bosch, Stefania Corti

{"title":"Using human 3D organoid models to gain mechanistic insight in motor neuron diseases","authors":"Benedetta Frizzi, Adriana Margarida Barbosa Correia, Irene Faravelli, Ludo Van Den Bosch, Stefania Corti","doi":"10.1038/s41583-026-01057-x","DOIUrl":"10.1038/s41583-026-01057-x","url":null,"abstract":"Motor neuron diseases (MNDs) are caused by the progressive loss of motor neurons and eventually lead to paralysis and death. Once viewed as primarily neurocentric, MNDs are now recognized to be driven by intertwined cell-autonomous and non-cell-autonomous mechanisms. Dissecting these interactions is essential for developing effective therapies. Here, we describe induced pluripotent stem cell-derived 3D models that can be used to capture distinct aspects of MND pathology. We show that spinal cord organoids can be used to investigate cell-autonomous mechanisms and motor neuron–glia interactions (with axially elongated spinal cord organoids being particularly useful to study developmental vulnerability) as well as in 3D muscle and combined neuromuscular models to dissect muscle pathology and neuromuscular junction dismantling. In parallel, we discuss advances in bioengineering, machine learning and human trunk-like models, which together can begin to reproduce the coordinated co-development and spatial organization of the multiple tissues affected in MNDs. We discuss how these systems have advanced our understanding of disease mechanisms and highlight opportunities for drug repurposing. Finally, we propose a mechanism-informed and phenotype-informed framework to guide 3D model selection for future research and to prioritize promising avenues for therapeutic development. Motor neuron disorders involve complex interactions between multiple CNS cell types, which are challenging to model in 2D in vitro conditions. Frizzi and colleagues describe recent advances in induced pluripotent stem cell-based 3D (organoid) models of the spinal cord and neuromuscular junction, and outline their application in the investigation of disease mechanisms.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"27 9","pages":"597-617"},"PeriodicalIF":29.0,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148393396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Driving neuronal apoptosis 驱动神经元凋亡。

IF 29 1区医学

Nature Reviews Neuroscience Pub Date : 2026-07-06 DOI: 10.1038/s41583-026-01067-9

Darran Yates

引用次数: 0

What scrub jays have taught us about the neural intersection of memory and action selection 灌丛鸦教给我们的关于记忆和行动选择的神经交叉。

IF 29 1区医学

Nature Reviews Neuroscience Pub Date : 2026-07-06 DOI: 10.1038/s41583-026-01068-8

Laura A. Bradfield

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Boundary issues for multidimensional frameworks of representation 多维表示框架的边界问题。

IF 29 1区医学

Nature Reviews Neuroscience Pub Date : 2026-07-03 DOI: 10.1038/s41583-026-01064-y

Morten Overgaard, Asger Kirkeby-Hinrup

引用次数: 0

Reply to ‘Boundary issues for multidimensional frameworks of representation’ 回复“多维表示框架的边界问题”。

IF 29 1区医学

Nature Reviews Neuroscience Pub Date : 2026-07-03 DOI: 10.1038/s41583-026-01063-z

Stephan Pohl, Edgar Y. Walker, David L. Barack, Jennifer Lee, Rachel N. Denison, Ned Block, Florent Meyniel, Wei Ji Ma

引用次数: 0

Brain–spleen axis regulates learned fear 脑脾轴调节习得性恐惧。

IF 29 1区医学

Nature Reviews Neuroscience Pub Date : 2026-06-24 DOI: 10.1038/s41583-026-01062-0

Katherine Whalley

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Acetylcholine: a candidate substrate for hippocampal predictive learning? 乙酰胆碱：海马预测性学习的候选底物？

IF 29 1区医学

Nature Reviews Neuroscience Pub Date : 2026-06-23 DOI: 10.1038/s41583-026-01058-w

William de Cothi, Sarah Shipley, Caswell Barry

{"title":"Acetylcholine: a candidate substrate for hippocampal predictive learning?","authors":"William de Cothi, Sarah Shipley, Caswell Barry","doi":"10.1038/s41583-026-01058-w","DOIUrl":"10.1038/s41583-026-01058-w","url":null,"abstract":"Acetylcholine release in the hippocampus has been associated with diverse neural functions in learning and memory, including novelty, uncertainty detection, error correction, arousal and hidden state inference, while also modulating theta oscillations. Confronted with this plurality of roles, a unifying framework for interpreting cholinergic function is lacking. Recently, predictive models have emerged as a normative lens for understanding neural function, viewing the brain as learning to predict environmental dynamics. Within this framework, we propose that hippocampal acetylcholine serves as a fundamental learning signal, encoding state transition prediction errors — the magnitude of mismatches between predicted and actual transitions in environmental states. We suggest that, analogously to how dopamine signals reward prediction errors to guide value learning, acetylcholine guides structural learning, signalling state transition prediction errors. By condensing behaviour onto timescales amenable to spike-timing-dependent plasticity, theta sequences provide a potential substrate for calculating state transition prediction errors and driving the synaptic updates that revise the internal world model. Within the septo-hippocampal circuit, we propose that theta sequences relay predictions to the septum for comparison against observed state transitions, with the resulting cholinergic feedback gating plasticity in proportion to the mismatch. Plausibly, this mechanistic account unifies the diverse roles of acetylcholine, from novelty detection to hidden state inference, as aspects of a single computational principle — learning predictive internal world models from precisely-timed neural sequences. Predictive models have emerged as a normative lens for understanding neural function. In this Perspective, de Cothi, Shipley and Barry plausibly unify the diverse roles of hippocampal acetylcholine in learning and memory by proposing it serves as a fundamental learning signal, encoding the mismatch between predicted and actual environmental state transitions.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"27 9","pages":"637-651"},"PeriodicalIF":29.0,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148305078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Astrocytes viewed through the lens of their proteomes and subproteomes 星形胶质细胞的蛋白质组和亚蛋白质组。

IF 29 1区医学

Nature Reviews Neuroscience Pub Date : 2026-06-23 DOI: 10.1038/s41583-026-01054-0

Vanessa H. Casha, Ling Wu, James A. Wohlschlegel, Baljit S. Khakh

{"title":"Astrocytes viewed through the lens of their proteomes and subproteomes","authors":"Vanessa H. Casha, Ling Wu, James A. Wohlschlegel, Baljit S. Khakh","doi":"10.1038/s41583-026-01054-0","DOIUrl":"10.1038/s41583-026-01054-0","url":null,"abstract":"Astrocytes are morphologically complex and functionally diverse glial cells that play central roles in neural circuits and disease. Although transcriptomic and physiological analyses have advanced understanding of astrocyte function, the intricacies of the relationship between gene expression and protein levels remains poorly understood. Proteins, rather than transcripts, execute the molecular processes that define astrocyte function, often within specialized subcellular compartments whose molecular composition has remained largely unresolved. Recent advances with genetically encoded proximity-dependent biotinylation have enabled mapping of astrocyte proteomes and subproteomes, revealing the spatial organization of protein networks that underpin astrocyte identity and function. In this Review we summarize strategies for defining astrocyte proteomes and subproteomes, emphasizing methodological innovations that permit cell-type-specific and spatially resolved proteomic profiling within intact neural tissue. The use of these approaches is shaping understanding of astrocyte biology by uncovering the molecular nature of their distributed physiology and the molecular basis of their interactions with neurons and other cells. Viewing astrocytes through a proteomic lens is beginning to help elucidate the molecular determinants of their morphology, signalling, and roles in homeostasis and disease. Such insights should enable detailed mechanistic understanding of astrocyte function and identify new avenues for targeting astrocytic contributions to brain disorders. Recent technological advances have provided novel understanding of the spatiotemporal relationship between gene expression and protein levels. In this Review, Khakh and colleagues summarize recent work on astrocyte proteomes and subproteomes, emphasizing methodological breakthroughs and new biological insights relevant to fundamental astrocyte biology in neural circuits.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"27 8","pages":"529-550"},"PeriodicalIF":29.0,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148305079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

m6A in RNA: a key regulator of brain development, function and disease RNA中的m6A：大脑发育、功能和疾病的关键调节因子。

IF 29 1区医学

Nature Reviews Neuroscience Pub Date : 2026-06-22 DOI: 10.1038/s41583-026-01056-y

Enakshi Sivasudhan, Kate D. Meyer

{"title":"m6A in RNA: a key regulator of brain development, function and disease","authors":"Enakshi Sivasudhan, Kate D. Meyer","doi":"10.1038/s41583-026-01056-y","DOIUrl":"10.1038/s41583-026-01056-y","url":null,"abstract":"Epitranscriptomic regulation of cellular RNAs is a major mechanism of gene expression control in the brain. N6-Methyladenosine (m6A) is installed on thousands of mRNAs and non-coding RNAs, where it functions as a context-dependent regulator of RNA–protein interactions to control the amplitude and kinetics of gene expression. In the nervous system, m6A is critical for neurodevelopment, synaptic plasticity and adaptive responses to physiological stimuli, and its dysregulation has been linked to various brain disorders. In this Review, we present a comprehensive synthesis of how m6A is deposited, interpreted and dynamically regulated, and integrate recent advances to present a unified framework for its function in neural cells. We discuss how m6A coordinates RNA stability, translation, localization and chromatin-associated processes across developmental and adult contexts and how disruption of these pathways contributes to neurological disease. Finally, we explore challenges and future directions for the field. N6-Methyladenosine (m6A) is installed on many mRNAs and non-coding RNAs and regulates gene expression by affecting RNA–protein interactions. In this Review, Enakshi Sivasudhan and Kate Meyer discuss how m6A is dynamically regulated and interpreted, and examine its role in brain function and disorders.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"27 8","pages":"571-590"},"PeriodicalIF":29.0,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148298922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Heading into the wild: setting the course to natural neuroscience 进入野外：设置自然神经科学的课程。

IF 29 1区医学

Nature Reviews Neuroscience Pub Date : 2026-06-17 DOI: 10.1038/s41583-026-01059-9

M. Jerome Beetz

引用次数: 0