Astrocytes as vital cells in the central nervous system are crucial for brain health and function. Recent research indicates that they influence higher cognitive functions and behaviors by regulating local neuronal activity. In times of stress, both animals and humans evaluate risks to generate adaptive behaviors such as avoidance. Disruptions in this process, often seen in mental disorders, can lead to excessive risk aversion (e.g., anxiety, depression, and autism) or insufficient risk avoidance (e.g., substance abuse, and schizophrenia).  

However, the neural mechanisms underlying these disruptions are not fully understood. Although the basolateral amygdala (BLA) is associated with active avoidance, its specific regulatory role in risk assessment and subsequent behaviors remains unclear.  

Recently, researchers led by Prof. TU Jie at the Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Sciences conducted a study on astrocytes in the BLA to investigate their roles in regulating impaired risk assessment in mental disorders. The study was published in Neuron. 

In previous work, the researchers had utilized a unique transgenic mouse model, DISC1-N mutant transgenic mice, to uncover impaired avoidance responses in these mice when confronted with threats.  

In this study, the researchers employed single-nucleus RNA sequencing in conjunction with patch-clamp and real-time quantitative single-cell PCR techniques to identified a specific group of glutamatergic excitatory neurons expressing Wolfram syndrome 1 (WFS1) in the BLA. These neurons receive induced action potentials from nearby astrocytes. In DISC1-N mice, these neurons exhibit reduced firing capabilities and impaired interaction with astrocytes.  

By activating astrocytes in the BLA using optogenetics/chemogenetics methods and through D-serine's action on N-methyl-D-aspartic acid receptor (NMDA) receptors of BLA-WFS1 neurons, the researchers found that the excitability of these neurons can be restored, thereby improving abnormal risk assessment behavior in DISC1-N mice. They also observed that direct activation of BLA-WFS1 does not effectively correct the deficient risk avoidance behavior in DISC1-N mice.  

The study, conducted over a period of seven years, confirmed that specific neurons in the BLA require interaction with astrocytes to perform normal risk-assessment. This highlights the insufficiency of autonomous neuronal activity alone in carrying out relevant risk-assessment functions.   

Furthermore, the researchers revealed the disruption in astrocyte-neuron communication as a crucial mechanism contributing to deficits in risk- assessment.  

"Our study provides fresh evidence regarding the critical role of astrocytes in regulating behavior and presents novel therapeutic targets for addressing impairments in risk assessment function within mental disorders," said Prof. TU.