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 de...行为依赖于多个脑区间的协同活动。在这类脑网络中，高度连接的枢纽脑区被认为会不成比例地影响行为输出，不过这一假说尚未得到系统性验证。我们此前通过绘制全脑活动依赖基因c-fos（activity-regulated gene c-fos）的表达图谱，鉴定出了由恐惧记忆共同激活的脑区所构成的网络。为验证枢纽脑区对脑网络功能更为关键这一假说，本研究在该经行为学定义的功能网络中开展了计算机模拟（in silico）节点删除实验。删除高连接度节点会对网络造成最为显著的破坏（例如全局效率（global efficiency）下降）。为在体内（in vivo）验证上述预测结果，我们探究了训练后对不同网络节点进行化学遗传学（chemogenetic）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……