GSE262541 Astrocyte-mediated regulation of BLAWFS1 neurons alleviates risk-assessment deficits in DISC1-N mice

Contributors : Xinyi Zhou ; Qian Xiao ; Yaohui Liu ; Shuai Chen ; Xirong Xu ; Zhigang Zhang ; Yuchuan Hong ; Jie Shao ; Yuewen Chen ; Yu Chen ; Liping Wang ; Fan Yang ; Jie TuSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusAssessing and responding to threats is vital in everyday life. Unfortunately, many mental illnesses involve impaired risk assessment, affecting patients, families, and society. The brain processes behind these behaviors are not well understood. We developed a transgenic mouse model (DISC1-N) with a disrupted avoidance response in risky settings. Our study utilized single-nucleus RNA sequencing to uncover a previously undescribed group of glutamatergic neurons in the basolateral amygdala (BLA) marked by WFS1 expression, whose activity is modulated by adjacent astrocytes. These neurons in DISC1-N mice exhibited diminished firing ability and impaired communication with the astrocytes. Remarkably, optogenetic activation of these astrocytes reinstated neuronal excitability via D-serine acting on BLAWFS1 neurons ’ NMDA receptors, leading to improved risk-assessment behavior in the DISC1-N mice. Our findings point to BLA astrocytes as a promising target for treating risk assessment dysfunctions in mental disorders.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research