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功能连接组学揭示了小鼠视觉皮层的一般布线规则。

Functional connectomics reveals general wiring rule in mouse visual cortex.

作者信息

Ding Zhuokun, Fahey Paul G, Papadopoulos Stelios, Wang Eric Y, Celii Brendan, Papadopoulos Christos, Chang Andersen, Kunin Alexander B, Tran Dat, Fu Jiakun, Ding Zhiwei, Patel Saumil, Ntanavara Lydia, Froebe Rachel, Ponder Kayla, Muhammad Taliah, Bae J Alexander, Bodor Agnes L, Brittain Derrick, Buchanan JoAnn, Bumbarger Daniel J, Castro Manuel A, Cobos Erick, Dorkenwald Sven, Elabbady Leila, Halageri Akhilesh, Jia Zhen, Jordan Chris, Kapner Dan, Kemnitz Nico, Kinn Sam, Lee Kisuk, Li Kai, Lu Ran, Macrina Thomas, Mahalingam Gayathri, Mitchell Eric, Mondal Shanka Subhra, Mu Shang, Nehoran Barak, Popovych Sergiy, Schneider-Mizell Casey M, Silversmith William, Takeno Marc, Torres Russel, Turner Nicholas L, Wong William, Wu Jingpeng, Yin Wenjing, Yu Szi-Chieh, Yatsenko Dimitri, Froudarakis Emmanouil, Sinz Fabian, Josić Krešimir, Rosenbaum Robert, Seung H Sebastian, Collman Forrest, da Costa Nuno Maçarico, Reid R Clay, Walker Edgar Y, Pitkow Xaq, Reimer Jacob, Tolias Andreas S

机构信息

Center for Neuroscience and Artificial Intelligence and Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA.

Department of Ophthalmology and Byers Eye Institute, Stanford University School of Medicine, Stanford, CA, USA.

出版信息

Nature. 2025 Apr;640(8058):459-469. doi: 10.1038/s41586-025-08840-3. Epub 2025 Apr 9.

Abstract

Understanding the relationship between circuit connectivity and function is crucial for uncovering how the brain computes. In mouse primary visual cortex, excitatory neurons with similar response properties are more likely to be synaptically connected; however, broader connectivity rules remain unknown. Here we leverage the millimetre-scale MICrONS dataset to analyse synaptic connectivity and functional properties of neurons across cortical layers and areas. Our results reveal that neurons with similar response properties are preferentially connected within and across layers and areas-including feedback connections-supporting the universality of 'like-to-like' connectivity across the visual hierarchy. Using a validated digital twin model, we separated neuronal tuning into feature (what neurons respond to) and spatial (receptive field location) components. We found that only the feature component predicts fine-scale synaptic connections beyond what could be explained by the proximity of axons and dendrites. We also discovered a higher-order rule whereby postsynaptic neuron cohorts downstream of presynaptic cells show greater functional similarity than predicted by a pairwise like-to-like rule. Recurrent neural networks trained on a simple classification task develop connectivity patterns that mirror both pairwise and higher-order rules, with magnitudes similar to those in MICrONS data. Ablation studies in these recurrent neural networks reveal that disrupting like-to-like connections impairs performance more than disrupting random connections. These findings suggest that these connectivity principles may have a functional role in sensory processing and learning, highlighting shared principles between biological and artificial systems.

摘要

理解电路连接性与功能之间的关系对于揭示大脑如何进行计算至关重要。在小鼠初级视觉皮层中,具有相似反应特性的兴奋性神经元更有可能形成突触连接;然而,更广泛的连接规则仍然未知。在这里,我们利用毫米级的MICrONS数据集来分析跨皮层层和区域的神经元的突触连接性和功能特性。我们的结果表明,具有相似反应特性的神经元在层内和跨层及区域之间优先连接,包括反馈连接,这支持了“同类到同类”连接在视觉层级中的普遍性。使用经过验证的数字孪生模型,我们将神经元调谐分为特征(神经元对什么做出反应)和空间(感受野位置)成分。我们发现,只有特征成分能够预测超出轴突和树突接近程度所能解释的精细尺度突触连接。我们还发现了一个高阶规则,即突触前细胞下游的突触后神经元群体表现出比成对同类规则预测的更大的功能相似性。在简单分类任务上训练的循环神经网络发展出的连接模式反映了成对和高阶规则,其量级与MICrONS数据中的量级相似。对这些循环神经网络的消融研究表明,破坏同类连接比破坏随机连接对性能的损害更大。这些发现表明,这些连接原则可能在感觉处理和学习中具有功能作用,突出了生物系统和人工系统之间的共同原则。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d92/11981947/e6b48efca807/41586_2025_8840_Fig1_HTML.jpg

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