Why mice freeze or flee in the face of fear

What causes some people to freeze in their tracks in the face of danger – and why does anxiety cause others to do the same in times of safety?

Researchers in Europe and the US wanted to find out exactly what happens to our brain when we find ourselves stunned with fright in the hope of better understanding how fear interplays with human anxiety disorders.

For the first time, they traced and linked three parts of the brain responsible for freezing behaviours: the amygdala, ventrolateral periaqueductal grey region and magnocellular nucleus.

The work was published in the journal Nature.

Mice are excellent lab animals where it comes to anxiety and fear experiments. When a mouse is scared, its defensive behaviours range from freezing, attacking, risk assessment or fleeing the scene. How a mouse acts depends on variables such as access to escape routes or the level of threat faced.

So Andreas Lüthi at the Friedrich Miescher Institute for Biomedical Research in Switzerland and colleagues from Europe and the US observed brain activity in mice placed in frightening situations to trace the brain circuits responsible for freezing behaviours.

In particular, the researchers wanted to learn more about a part of the brain called the ventrolateral periaqueductal grey region, which was believed to play some part in a mouse’s instinct to freeze or flee.

To measure fear responses, test mice were placed in an open arena with a remote-controlled toy snake. Implanted brain probes did, indeed, pick up that activation of cells in the ventrolateral periaqueductal grey region led to mice freezing in fear.

They also traced neurons from the amygdala, a brain structure involved in learning and emotion, that feed into the ventrolateral periaqueductal grey region. That pathway mediates freezing in fear by, in turn, affecting a pathway to a part of the brain called the magnocellular nucleus, which is involved in motor coordination.

Usually, neurons running from the ventrolateral periaqueductal grey region to magnocellular nucleus are dialled down and motor coordination carries on as usual.

But when the ventrolateral periaqueductal grey region receives a fear signal, that inhibition is lifted and motor coordination goes out the window. The mouse freezes.

The freezing process also interacts with the brain circuits that can cause mice to flee, the researchers showed.

Interruption of these circuits can cause or contribute to anxiety disorders and other conditions in humans, they write, and cause them to select inappropriate defensive behaviours in the face of a threat.