Dag Ugur, Nwabudike Ijeoma, Kang Di, Gomes Matthew A, Kim Jungsoo, Atanas Adam A, Bueno Eric, Estrem Cassi, Pugliese Sarah, Wang Ziyu, Towlson Emma, Flavell Steven W
Picower Institute for Learning & Memory, Department of Brain & Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
These authors contributed equally to this work.
bioRxiv. 2023 Jan 18:2023.01.15.524132. doi: 10.1101/2023.01.15.524132.
Serotonin controls many aspects of animal behavior and cognition. But how serotonin acts on its diverse receptor types in neurons across the brain to modulate global activity and behavior is unknown. Here, we examine how serotonin release from a feeding-responsive neuron in alters brain-wide activity to induce foraging behaviors, like slow locomotion and increased feeding. A comprehensive genetic analysis identifies three core serotonin receptors that collectively induce slow locomotion upon serotonin release and three others that interact with them to further modulate this behavior. The core receptors have different functional roles: some induce behavioral responses to sudden increases in serotonin release, whereas others induce responses to persistent release. Whole-brain calcium imaging reveals widespread serotonin-associated brain dynamics, impacting different behavioral networks in different ways. We map out all sites of serotonin receptor expression in the connectome, which, together with synaptic connectivity, helps predict serotonin-associated brain-wide activity changes. These results provide a global view of how serotonin acts at defined sites across a connectome to modulate brain-wide activity and behavior.
血清素控制着动物行为和认知的许多方面。但血清素如何作用于大脑中不同类型的神经元受体，以调节整体活动和行为，目前尚不清楚。在这里，我们研究了秀丽隐杆线虫中一个对进食有反应的神经元释放的血清素如何改变全脑活动，以诱导觅食行为，如缓慢移动和增加进食。一项全面的基因分析确定了三种核心血清素受体，它们在血清素释放时共同诱导缓慢移动，还有另外三种受体与它们相互作用，进一步调节这种行为。核心受体具有不同的功能作用：一些诱导对血清素释放突然增加的行为反应，而另一些则诱导对持续释放的反应。全脑钙成像揭示了广泛的与血清素相关的脑动态，以不同方式影响不同的行为网络。我们在连接体中绘制了血清素受体表达的所有位点，这与突触连接性一起，有助于预测与血清素相关的全脑活动变化。这些结果提供了一个关于血清素如何在连接体中的特定位点起作用以调节全脑活动和行为的全局视图。
