Multi-scale analysis of psychological stress loaded brain: Deciphering the neural mechanisms of stress responses

Abstract

Stress responses are complex, involving function in various brain regions and neural circuits. However, their underlying mechanisms are not fully understood. In our recent study, we reported that claustrum activation serves as a reliable marker of exposure to acute stressors, using brain-wide activation mapping and unbiased classification. We conducted further investigations on role of stress-responsive neurons in the claustrum, employing chemo- and optogenetic manipulation techniques. In addition, we identified the molecular marker of these neurons using single-cell RNA sequencing. During freely moving calcium imaging, we found that a subset of claustrum neurons displayed an increase in calcium levels upon transitioning to aversive areas associated with increased anxiety. These findings suggest that a subset of the claustrum controls stress-induced emotional responses. Our study highlights the importance of a comprehensive brain-wide approach to understanding the complex nature of stress responses and the underlying neurobiological mechanisms.