Cutting-edge investigation sheds light on the indispensable role of astrocytes within the basolateral amygdala (BLA) in modulating risk assessment behaviors, often perturbed in mental disorders. Employing advanced methodologies, researchers delved into the influence of these brain cells on a specific cluster of neurons in the BLA crucial for threat evaluation.
The study, published in Neuron, showcases how activating astrocytes can ameliorate aberrant behaviors in genetically engineered mice, shedding new light on the cellular dynamics underpinning mental health conditions. This research underscores the potential of targeting astrocyte-neuron interactions as a therapeutic avenue for disorders characterized by distorted risk behaviors.
Here are the key findings:
Focus on Astrocytes in the BLA: The research zoomed in on astrocytes within the BLA, a pivotal brain region governing responses to threats.
Astrocyte Activity Correction: Through boosting astrocyte activity, researchers corrected abnormal risk assessment behaviors in a mouse model mirroring mental disorders.
Significance of Astrocyte-Neuron Interactions: The study underscores the pivotal role of astrocyte-neuron interactions in the brain’s risk assessment mechanism, opening new vistas for therapeutic interventions in mental health.
Astrocytes, integral to central nervous system function, play a vital role in maintaining brain health and function. Recent scientific inquiries indicate their influence on higher cognitive functions and behaviors by modulating local neuronal activity.
During stressful situations, both animals and humans evaluate risks to devise adaptive responses like avoidance. Mental disorders often disrupt this process, manifesting as excessive risk aversion (e.g., anxiety, depression, and autism) or inadequate risk avoidance (e.g., substance abuse, and schizophrenia).
However, the neural underpinnings of these disruptions remain partially understood. While the BLA is recognized for its involvement in active avoidance, its specific regulatory role in risk assessment and ensuing behaviors remained ambiguous.
Prof. Tu Jie’s team at the Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Sciences endeavored to unravel the role of astrocytes in the BLA in modulating impaired risk assessment in mental disorders.
Previously, researchers utilized a unique transgenic mouse model, DISC1-N mutant transgenic mice, to uncover impaired avoidance responses in the face of threats.
In this latest study, researchers employed single-nucleus RNA sequencing along with patch-clamp and real-time quantitative single-cell PCR techniques to identify a specific cluster of glutamatergic excitatory neurons expressing Wolfram syndrome 1 (WFS1) in the BLA. These neurons received induced action potentials from neighboring astrocytes. In DISC1-N mice, these neurons exhibited reduced firing capabilities and impaired interaction with astrocytes.
Through the activation of astrocytes in the BLA via optogenetics/chemogenetics methods and D-serine’s action on the N-methyl-D-aspartic acid (NMDA) receptors of BLA-WFS1 neurons, researchers restored the excitability of these neurons, consequently improving abnormal risk assessment behavior in DISC1-N mice.
Moreover, the study highlighted the insufficiency of autonomous neuronal activity alone in carrying out relevant risk-assessment functions, emphasizing the critical role of astrocyte-neuron communication in this process.
Prof. Tu remarked, “Our study provides compelling evidence of the pivotal role of astrocytes in behavior regulation and identifies novel therapeutic targets for addressing impairments in risk assessment function within mental disorders.”
