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

Noriko Horii-Hayashi; Kensaku Nomoto; Nozomi Endo; Akihiro Yamanaka; Takefumi Kikusui; Mayumi Nishi

doi:10.1016/j.isci.2020.101908

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

iScience. 2020 Dec 9;24(1):101908. doi: 10.1016/j.isci.2020.101908. eCollection 2021 Jan 22.

Authors

Noriko Horii-Hayashi¹, Kensaku Nomoto^{2

3}, Nozomi Endo¹, Akihiro Yamanaka⁴, Takefumi Kikusui², Mayumi Nishi¹

Affiliations

¹ Department of Anatomy and Cell Biology, Nara Medical University, Kashihara, Nara 643-8521, Japan.
² Companion Animal Research Laboratory, School of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa 252-5201, Japan.
³ Department of Physiology, Dokkyo Medical University, Mibu, Tochigi, 321-0293, Japan.
⁴ Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan.

Abstract

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.

Keywords: Behavioral Neuroscience; Biological Sciences; Neuroscience.