A psychological stressor conveyed by appetite-linked neurons Mammals exhibit instinctive reactions to danger that include specific behaviors as well as surges in blood stress hormones that rally multiple tissues to cope with threat. Hypothalamic corti- cotropin releasing hormone neurons (CRHNs) are master regulators of stress hormones, but how varied stress and danger signals con- verge on these neurons to elicit a stress response is unknown. Here we used single cell transcriptomics to identify receptors for neurotransmitters and neuromodulators on CRHNs and then viral tracing to localize subsets of upstream neurons expressing lig- ands of those receptors. Surprisingly, one subset comprised POMC (pro-opiomelanocortin)-expressing neurons in the hypothalamic arcuate nucleus, which are linked to appetite suppression. The POMC neurons were activated by physical restraint, a psycholog- ical stressor. Chemogenetic activation of POMC neurons induced a stress hormone increase and their silencing inhibited the stress hormone response to restraint, but not a predator odor stressor. Together, these results indicate that hypothalamic POMC neurons, which are implicated in appetite suppression, also play a major and selective role in the stress hormone response to a specific type of psychological stressor.
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