RT Journal Article SR Electronic T1 Multiple overlapping hypothalamus-brainstem circuits drive rapid threat avoidance JF bioRxiv FD Cold Spring Harbor Laboratory SP 745075 DO 10.1101/745075 A1 Matthew Lovett-Barron A1 Ritchie Chen A1 Susanna Bradbury A1 Aaron S Andalman A1 Mahendra Wagle A1 Su Guo A1 Karl Deisseroth YR 2019 UL http://biorxiv.org/content/early/2019/08/24/745075.abstract AB Animals survive environmental challenges by adapting their physiology and behavior through homeostatic regulatory processes, mediated in part by specific neuropeptide release from the hypothalamus. Animals can also avoid environmental stressors within seconds, a fast behavioral adaptation for which hypothalamic involvement is not established. Using brain-wide neural activity imaging in behaving zebrafish, here we find that hypothalamic neurons are rapidly engaged during common avoidance responses elicited by various environmental stressors. By developing methods to register cellular-resolution neural dynamics to multiplexed in situ gene expression, we find that each category of stressor recruits similar combinations of multiple peptidergic cell types in the hypothalamus. Anatomical analysis and functional manipulations demonstrate that these diverse cell types play shared roles in behavior, are glutamatergic, and converge upon spinal-projecting brainstem neurons required for avoidance. These data demonstrate that hypothalamic neural populations, classically associated with slow and specific homeostatic adaptations, also together give rise to fast and generalized avoidance behavior.