Researchers Highlight Crucial Contributions of Astrocytes to Mental Health

The health and function of the brain depend on astrocytes, which are essential cells in the central nervous system. According to recent research, they affect behaviors and higher cognitive functions by controlling local neuronal activity.

Both humans and animals evaluate hazards in times of stress and respond with adaptive behaviors like avoidance. A lot of mental illnesses interfere with this process, causing either too much risk avoidance (like in substance abuse and schizophrenia) or too much risk aversion (like in anxiety, depression, and autism).

It is unclear, nevertheless, exactly where these disruptions originate from in the brain. Although the basolateral amygdala (BLA) is associated with active avoidance, it is unclear what precise regulatory function it plays in risk assessment and subsequent behavior.

Astrocytes in the BLA were the subject of a recent study by Prof. Jie Tu’s group at the Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Sciences, which looked into their functions in controlling impaired risk assessment in mental disorders. The study was published in the journal Neuron.

Researchers discovered compromised avoidance responses in these mice when faced with threats in earlier work using a special transgenic mouse model called DISC1-N mutant transgenic mice.

To find a particular subset of glutamatergic excitatory neurons expressing Wolfram syndrome 1 (WFS1) in the BLA, researchers used single-nucleus RNA sequencing in combination with patch-clamp and real-time quantitative single-cell PCR techniques. Not far away astrocytes generated action potentials that were sent to these neurons. Neurons in DISC1-N mice showed decreased firing capacity and decreased astrocyte interaction.

Through the application of optogenetics/chemogenetics to activate astrocytes in the BLA, as well as D-serine's action on the N-methyl-D-aspartic acid (NMDA) receptors of BLA-WFS1 neurons, researchers discovered that abnormal risk assessment behavior in DISC1-N mice can be improved by restoring the excitability of these neurons. Additionally, they found that BLA-WFS1 cannot be directly activated to improve the DISC1-N mice’s poor risk avoidance behavior.

It has been determined, after seven years of intensive research, that certain neurons in the BLA need to interact with astrocytes in order to perform normal risk-assessment. This finding emphasizes the inadequacy of autonomous neuronal activity in performing pertinent risk-assessment functions on its own. Furthermore, they identified astrocyte-neuron communication disruption as a critical mechanism behind deficits in risk assessment.

Our study offers evidence of the critical role of astrocytes in regulating behavior, and presents novel therapeutic targets for addressing impairments in risk assessment function within mental disorders.”

Jie Tu, Professor, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences

Source:
Journal reference:

Zhou, X., et al. (2024) Astrocyte-mediated regulation of BLAWFS1 neurons alleviates risk-assessment deficits in DISC1-N mice. Neuron. doi.org/10.1016/j.neuron.2024.03.028

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