Long-term stress is well known to cause major psychological issues.

However, the exact mechanisms that make people react to stress haven’t been very clear.

Researchers from Japan have discovered a small set of brain cells that control stress-induced responses thanks to recent breakthroughs in microscopic imaging.

These cells may hold the key to unraveling the causes of stress-related mental illnesses.

Scientists from Osaka University uncovered a small group of brain cells in the claustrum of mice that regulates stress-induced anxiety behaviors in a study published this month in Science Advances.

Mice showed anxiety-related behaviors when these cells were triggered via chemogenetic technology, whereas deactivating the cells rendered mice more tolerant to chronic stress.

Because of technical restrictions, identifying such small populations of cells using an unbiased and hypothesis-free approach has been difficult until recently.

This has now been made possible thanks to the recent discovery of block-face serial microscopy tomography (known as FAST) by experts at Osaka University. The researchers were able to study changes in cellular activity at the level of a single cell using this technique.

The processing of stress is well acknowledged to be dependent on communication between cortical and subcortical brain regions; however, the specific mechanism underlying this connection is unknown, which is what the researchers hoped to discover with this technique.

The researchers mapped patterns of cellular activity in stressed mice using well-established psychological animal models of constraint and social defeat stress. The researchers took whole-brain pictures of control mice and mice subjected to these stressful settings using the FAST technique.

The claustrum was identified as a critical region that distinguished stressed from non-stressed brains.

“A combined approach using brain activation mapping and machine learning showed that the claustrum activation serves as a reliable marker of exposure to acute stressors,” said lead authors Misaki Niu and Atsushi Kasai.

Importantly, they found that the claustrum is critical in controlling stress-induced anxious behaviors through chemogenetic manipulation of these cells’ activity. Mice with increased claustrum cell activity displayed anxious behaviors, which could be reversed by reducing claustrum cell activity.

“Inactivation of stress-responsive claustrum neurons can serve as at least a partially preventative measure for the emergence of depression-like behavior, and moreover, for stress susceptibility to increase resilience to emotional stress,” explained senior author Hitoshi Hashimoto.

This groundbreaking discovery paves the way for claustrum activity to be used as a new therapy target for anxiety disorders, as well as a better understanding of the causes of stress-related diseases.

Source: 10.1126/sciadv.abi6375

Image Credit: Getty

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