PMID- 37808690 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240115 DP - 2024 Jan 12 TI - Hypothalamic representation of the imminence of predator threat detected by the vomeronasal organ in mice. LID - 2023.09.27.559655 [pii] LID - 10.1101/2023.09.27.559655 [doi] AB - Animals have the innate ability to select optimal defensive behavioral outputs with an appropriate intensity in response to predator threat in specific contexts. Such innate behavioral decisions are thought to be computed in the medial hypothalamic nuclei that contain neural populations directly controlling defensive behavioral outputs. The vomeronasal organ (VNO) is one of the major sensory input channels through which predator cues are detected with ascending inputs to the medial hypothalamic nuclei, especially to the ventromedial hypothalamus (VMH), through the medial amygdala (MeA) and bed nucleus of the stria terminalis (BNST). Here, we show that cat saliva contains predator cues that signal imminence of predator threat and regulate the robustness of freezing behavior through the VNO in mice. Cat saliva activates neurons expressing the V2R-A4 subfamily of sensory receptors, suggesting the existence of specific receptor groups responsible for freezing behavior induced by the predator cues. The number of VNO neurons activated in response to saliva correlates with the freshness of saliva and the intensity of freezing behavior, while the downstream neurons in the accessory olfactory bulb (AOB) and defensive behavioral circuit are quantitatively equally activated by fresh and old saliva. Strikingly, however, only the number of VMH neurons activated by fresh saliva positively correlates with the intensity of freezing behavior. Detailed analysis of the spatial distribution of fresh and old saliva-responding neurons revealed a neuronal population within the VMH that is more sensitive to fresh saliva than old saliva. Taken together, this study demonstrates that predator cues in cat saliva change over time and differentially activate the sensory-to-hypothalamus defensive behavioral pathway to modulate behavioral outputs. FAU - Nguyen, Quynh Anh Thi AU - Nguyen QAT FAU - Rocha, Andrea AU - Rocha A FAU - Yamashita, Yuna AU - Yamashita Y FAU - Chhor, Ricky AU - Chhor R FAU - Stadler, Christian AU - Stadler C FAU - Pontrello, Crystal AU - Pontrello C FAU - Haga-Yamanaka, Sachiko AU - Haga-Yamanaka S AUID- ORCID: 0000-0002-4101-9889 LA - eng GR - R01 DC019135/DC/NIDCD NIH HHS/United States PT - Preprint DEP - 20240112 PL - United States TA - bioRxiv JT - bioRxiv : the preprint server for biology JID - 101680187 PMC - PMC10557655 EDAT- 2023/10/09 06:41 MHDA- 2023/10/09 06:42 PMCR- 2024/01/12 CRDT- 2023/10/09 05:43 PHST- 2023/10/09 06:41 [pubmed] PHST- 2023/10/09 06:42 [medline] PHST- 2023/10/09 05:43 [entrez] PHST- 2024/01/12 00:00 [pmc-release] AID - 2023.09.27.559655 [pii] AID - 10.1101/2023.09.27.559655 [doi] PST - epublish SO - bioRxiv [Preprint]. 2024 Jan 12:2023.09.27.559655. doi: 10.1101/2023.09.27.559655.