A circuit from the ventral subiculum to anterior hypothalamic nucleus GABAergic neurons essential for anxiety-like behavioral avoidance

• Published in: Nature communications Vol. 13; no. 1; p. 7464
• Main Authors: Yan, Jing-Jing, Ding, Xiao-Jing, He, Ting, Chen, Ai-Xiao, Zhang, Wen, Yu, Zi-Xian, Cheng, Xin-Yu, Wei, Chuan-Yao, Hu, Qiao-Dan, Liu, Xiao-Yao, Zhang, Yan-Li, He, Mengge, Xie, Zhi-Yong, Zha, Xi, Xu, Chun, Cao, Peng, Li, Haohong, Xu, Xiao-Hong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.12.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 14/19; 14/32; 631/378/1457/1601; 631/378/1697/1691; 631/378/3920; 64/60; 9/10; 9/74; 9/97; Animals; Anterior Hypothalamic Nucleus; Anxiety; Anxiety Disorders; Avoidance; Avoidance behavior; Behavior; Circuits; Defense; GABAergic Neurons; Hippocampus; Humanities and Social Sciences; Hypothalamus; Male; Mice; multidisciplinary; Neurons; Predators; Science; Science (multidisciplinary); Subiculum; γ-Aminobutyric acid
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-35211-7

Behavioral observations suggest a connection between anxiety and predator defense, but the underlying neural mechanisms remain unclear. Here we examine the role of the anterior hypothalamic nucleus (AHN), a node in the predator defense network, in anxiety-like behaviors. By in vivo recordings in male mice, we find that activity of AHN GABAergic (AHN Vgat+ ) neurons shows individually stable increases when animals approach unfamiliar objects in an open field (OF) or when they explore the open-arm of an elevated plus-maze (EPM). Moreover, object-evoked AHN activity overlap with predator cue responses and correlate with the object and open-arm avoidance. Crucially, exploration-triggered optogenetic inhibition of AHN Vgat+ neurons reduces object and open-arm avoidance. Furthermore, retrograde viral tracing identifies the ventral subiculum (vSub) of the hippocampal formation as a significant input to AHN Vgat+ neurons in driving avoidance behaviors in anxiogenic situations. Thus, convergent activation of AHN Vgat+ neurons serves as a shared mechanism between anxiety and predator defense to promote behavioral avoidance. Anxiety is thought to be evolutionarily rooted in predator defense. Yan et al. show that GABAergic neurons in the anterior hypothalamic nucleus (AHN), a node in the predator defense network, play an essential role in anxiety-like behaviors.