Claustrum mediates bidirectional and reversible control of stress-induced anxiety responses
Misaki Niu, Atsushi Kasai, Masato Tanuma, Kaoru Seiriki, Hisato Igarashi, Takahiro Kuwaki, Kazuki Nagayasu, Keita Miyaji, Hiroki Ueno, Wataru Tanabe, Kei Seo, Rei Yokoyama, Jin Ohkubo, Yukio Ago, Misuzu Hayashida, Ken‐ichi Inoue, Masahiko Takada, Shun Yamaguchi, Takanobu Nakazawa, Shuji Kaneko, Hiroyuki Okuno, Akihiro Yamanaka, Hitoshi Hashimoto
Abstract
The processing of stress responses involves brain-wide communication among cortical and subcortical regions; however, the underlying mechanisms remain elusive. Here, we show that the claustrum (CLA) is crucial for the control of stress-induced anxiety-related behaviors. A combined approach using brain activation mapping and machine learning showed that the CLA activation serves as a reliable marker of exposure to acute stressors. In TRAP2 mice, which allow activity-dependent genetic labeling, chemogenetic activation of the CLA neuronal ensemble tagged by acute social defeat stress (DS) elicited anxiety-related behaviors, whereas silencing of the CLA ensemble attenuated DS-induced anxiety-related behaviors. Moreover, the CLA received strong input from DS-activated basolateral amygdala neurons, and its circuit-selective optogenetic photostimulation temporarily elicited anxiety-related behaviors. Last, silencing of the CLA ensemble during stress exposure increased resistance to chronic DS. The CLA thus bidirectionally controls stress-induced emotional responses, and its inactivation can serve as a preventative strategy to increase stress resilience.