Data from: Chemogenetic interrogation of a brain-wide fear memory network in mice

Behavior depends on coordinated activity across multiple brain regions. Within such networks, highly connected hub regions are assumed to disproportionately influence behavioral output, although this hypothesis has not been systematically evaluated. Previously, by mapping brain-wide expression of the activity-regulated gene c-fos, we identified a network of brain regions co-activated by fear memory. To test the hypothesis that hub regions are more important for network function, here, we simulated node deletion in silico in this behaviorally defined functional network. Removal of high degree nodes produced the greatest network disruption (e.g., reduction in global efficiency). To test these predictions in vivo, we examined the impact of post-training chemogenetic silencing of different network nodes on fear memory consolidation. In a series of independent experiments encompassing 25% of network nodes (i.e., 21/84 brain regions), we found that node degree accurately predicted observed deficits in memory consolidation, with silencing of highly connected hubs producing the largest impairments.

行为依赖于多个脑区之间的协同活动。在这类脑网络中，高度连接的枢纽脑区（hub regions）被认为会不成比例地影响行为输出，尽管这一假说尚未得到系统性评估。此前，我们通过绘制活动依赖基因c-fos（activity-regulated gene c-fos）的全脑表达谱，鉴定出了恐惧记忆共激活的脑区网络。为验证枢纽脑区对脑网络功能更为关键这一假说，我们在该基于行为学定义的功能网络中开展了计算机模拟（in silico）的节点删除实验。移除高连接度节点会造成最显著的网络破坏，例如全局效率（global efficiency）降低。为在体内验证上述预测结果，我们检测了训练后对不同网络节点进行化学遗传学沉默对恐惧记忆巩固的影响。在一系列覆盖25%网络节点（即84个脑区中的21个）的独立实验中，我们发现节点连接度能够准确预测实验中观察到的记忆巩固缺陷，其中对高度连接的枢纽脑区进行沉默会引发最严重的功能损伤。