The hypothalamus is composed of many neuropeptidergic cell populations and directs multiple survival behaviors, including defensive responses to threats. However, the relationship between the peptidergic identity of neurons and their roles in behavior remains unclear. Here, we address this issue by studying the function of multiple neuronal populations in the zebrafish hypothalamus during defensive responses to a variety of homeostatic threats. Cellular registration of large-scale neural activity imaging to multiplexed in situ gene expression revealed that neuronal populations encoding behavioral features encompass multiple overlapping sets of neuropeptidergic cell classes. Manipulations of different cell populations showed that multiple sets of peptidergic neurons play similar behavioral roles in this fast-timescale behavior through glutamate co-release and convergent output to spinal-projecting premotor neurons in the brainstem. Our findings demonstrate that homeostatic threats recruit neurons across multiple hypothalamic cell populations, which cooperatively drive robust defensive behaviors.

下丘脑由许多神经肽能细胞群组成，指导多种生存行为，包括对威胁的防御反应。然而，神经元的肽能特性与其在行为中的作用之间的关系仍不清楚。在这里，我们通过研究斑马鱼下丘脑中多个神经元群在对各种稳态威胁的防御反应期间的功能来解决这个问题。大规模神经活动成像与多重原位基因表达的细胞配准表明，编码行为特征的神经元群体包含多个重叠的神经肽能细胞类别。对不同细胞群的操作表明，多组肽能神经元通过谷氨酸共同释放和汇聚输出到脑干中的脊髓投射前运动神经元，在这种快速时间尺度的行为中发挥相似的行为作用。我们的研究结果表明，稳态威胁会招募多个下丘脑细胞群中的神经元，这些神经元共同驱动强大的防御行为。