Theranostics 2021; 11(8):3813-3829. doi:10.7150/thno.45690

Research Paper

Paraventricular thalamic nucleus plays a critical role in consolation and anxious behaviors of familiar observers exposed to surgery mice

Qiuting Zeng1,2*, Weiran Shan1*, Hui Zhang1,2*, Jianjun Yang1,3, Zhiyi Zuo1✉

1. Department of Anesthesiology, University of Virginia, Charlottesville, VA 22908, U.S.A.
2. Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
3. Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China.
* These authors contributed equally.

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Zeng Q, Shan W, Zhang H, Yang J, Zuo Z. Paraventricular thalamic nucleus plays a critical role in consolation and anxious behaviors of familiar observers exposed to surgery mice. Theranostics 2021; 11(8):3813-3829. doi:10.7150/thno.45690. Available from

File import instruction


Background: Consolation behaviors toward the sick are common in humans. Anxiety in the relatives of the sick is also common. Anxiety can cause detrimental effects on multiple systems. However, our understanding on the neural mechanisms of these behaviors is limited because of the lack of small animal models.

Methods: Five of 6- to 8-week-old CD-1 male mice were housed in a cage. Among them, 2 mice had right common artery exposure (surgery) and the rest were without surgery. Allo-grooming and performance in light and dark box and elevated plus maze tests of the mice were determined.

Results: Mice without surgery had increased allo-grooming toward mice with surgery but decreased allo-grooming toward non-surgery intruders. This increased allo-grooming toward surgery mice was higher in familiar observers of surgery mice than that of mice that were not cage-mates of surgery mice before the surgery. Familiar observers developed anxious behavior after being with surgery mice. Surgery mice with familiar observers had less anxious behavior than surgery mice without interacting with familiar observers. Multiple brain regions including paraventricular thalamic nucleus (PVT) were activated in familiar observers. The activated cells in PVT contained orexin receptors. Injuring the neurons with ibotenic acid, antagonizing orexin signaling with an anti-orexin antibody or inhibiting neurons by chemogenetic approach in PVT abolished the consolation and anxious behaviors of familiar observers.

Conclusions: Mice show consolation behavior toward the sick. This behavior attenuates the anxious behavior of surgery mice. The orexin signaling in the PVT neurons play a critical role in the consolation of familiar observers toward surgery mice and their anxious behavior. Considering that about 50 million patients have surgery annually in the United States, our study represents the initial attempt to understand neural mechanisms for consolation and anxiety of a large number of people.

Keywords: anxious behavior, consolation behavior, mice, orexin, paraventricular thalamic nucleus, surgery.