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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, Alexander Bae J, 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, Sebastian Seung H, Collman Forrest, da Costa Nuno Maçarico, Clay Reid R, Walker Edgar Y, Pitkow Xaq, Reimer Jacob, Tolias Andreas S

机构信息

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

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

出版信息

bioRxiv. 2024 Oct 14:2023.03.13.531369. doi: 10.1101/2023.03.13.531369.

Abstract

Understanding the relationship between circuit connectivity and function is crucial for uncovering how the brain implements computation. In the mouse primary visual cortex (V1), excitatory neurons with similar response properties are more likely to be synaptically connected, but previous studies have been limited to within V1, leaving much unknown about broader connectivity rules. In this study, we leverage the millimeter-scale MICrONS dataset to analyze synaptic connectivity and functional properties of individual neurons across cortical layers and areas. Our results reveal that neurons with similar responses are preferentially connected both within and across layers and areas - including feedback connections - suggesting the universality of the '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 physical proximity of axons and dendrites. We also found a higher-order rule where postsynaptic neuron cohorts downstream of individual presynaptic cells show greater functional similarity than predicted by a pairwise like-to-like rule. Notably, recurrent neural networks (RNNs) trained on a simple classification task develop connectivity patterns mirroring both pairwise and higher-order rules, with magnitude similar to those in the MICrONS data. Lesion studies in these RNNs reveal that disrupting 'like-to-like' connections has a significantly greater impact on performance compared to lesions of random connections. These findings suggest that these connectivity principles may play 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实现计算至关重要。在小鼠初级视觉皮层(V1)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,但先前的研究仅限于V1内部,对于更广泛的连接规则仍知之甚少。在本研究中,我们利用毫米级的MICrONS数据集来分析跨皮层层和区域的单个神经元的突触连接性和功能特性。我们的结果表明,具有相似反应的神经元在层内和层间以及区域间(包括反馈连接)都优先连接,这表明“同类相联”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精细尺度的突触连接,这超出了轴突和树突物理 proximity 所能解释的范围。我们还发现了一个高阶规则,即单个突触前细胞下游的突触后神经元群体表现出比成对的同类相联规则所预测的更大的功能相似性。值得注意的是,在简单分类任务上训练的循环神经网络(RNN)发展出的连接模式反映了成对和高阶规则,其幅度与MICrONS数据中的相似。对这些RNN进行的损伤研究表明,与随机连接的损伤相比,破坏“同类相联”连接对性能的影响要大得多。这些发现表明,这些连接原则可能在感觉处理和学习中发挥功能作用,突出了生物和人工系统之间的共同原则。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f5a/11495362/754363fb6154/nihpp-2023.03.13.531369v3-f0001.jpg

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