Hypothalamic perifornical Urocortin-3 neurons modulate defensive responses to a potential threat stimulus

• Published in: iScience 2021-01, Vol.24 (1), p.101908-101908, Article 101908
• Main Authors: Horii-Hayashi, Noriko, Nomoto, Kensaku, Endo, Nozomi, Yamanaka, Akihiro, Kikusui, Takefumi, Nishi, Mayumi
• Format: Article
• Language: English
• Subjects: Behavioral Neuroscience; Biological Sciences; Neuroscience
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2020.101908

Defensive behaviors are evolved responses to threat stimuli, and a potential threat elicits risk assessment (RA) behavior. However, neural mechanisms underlying RA behavior are hardly understood. Urocortin-3 (Ucn3) is a member of corticotropin-releasing factor peptide family and here, we report that Ucn3 neurons in the hypothalamic perifornical area (PeFA) are involved in RA of a novel object, a potential threat stimulus, in mice. Histological and in vivo fiber photometry studies revealed that the activity of PeFA Ucn3 neurons was associated with novel object investigation involving the stretch-attend posture, a behavioral marker for RA. Chemogenetic activation of these neurons increased RA and burying behaviors toward a novel object without affecting anxiety and corticosterone levels. Ablation of these neurons caused the abnormal behaviors of gnawing and direct contacts with novel objects, especially in a home-cage. These results suggest that PeFA Ucn3 neurons modulate defensive responses to a potential threat stimulus. [Display omitted] •The activity of PeFA Ucn3 neurons is associated with novel object investigation•DREADD activation of PeFA Ucn3 neurons increases RA and burying of novel objects•Ablation of PeFA Ucn3 neurons causes direct contact with a novel object•PeFA Ucn3 neurons modulate defensive responses to novel objects Biological Sciences; Neuroscience; Behavioral Neuroscience