When faced with a threat, we have two options: freeze or run. Choosing the right defense can be critical for survival. Now, new research has identified the neural pathways that control this decision in animals, offering insight into what might go wrong in anxiety disorders like post-traumatic stress disorder (PTSD).

For years, researchers have used mice to study how fear is encoded in the brain. But most of the work has explored the so-called “passive” fear response, in which animals freeze when they feel threatened. The neurons that control the active fear response, driving animals away from danger, have remained largely unknown.

Published in Nature on February 2, 2017, a research team defines the neurons that control the flight response and proposes how neural circuits in the brain interact to determine if an animal chooses to stay or run.

The team was led by Jonathan Paul Fadok, Ph.D., a 2014 NARSAD Young Investigator grantee, and Andreas Luthi, Ph.D., a 2008 NARSAD Independent Investigator grantee. They found that both active and passive fear responses are controlled in a region of the brain known as the central amygdala. But distinct types of neurons are involved in each reaction. A group called CRF+ neurons control the flight reaction, while SOM+ neurons cause the animals to freeze.

Both CRF+ and SOM+ neurons are part of the larger class of inhibitory neurons, that is, cells that tamp down the signals of other nearby neurons. The researchers found that these two groups of neurons promote their own unique fear response in part by acting on one other to stifle the opposing fear reaction.

The results provide insight into how the brain processes fear and danger, revealing critical neural circuits that may be disrupted in anxiety and stress disorders.

The research team also included Sabine Krabbe, Ph.D., a 2015 NARSAD Young Investigator grantee; Chun Xu, M.D., Ph.D., a 2007 NARSAD Young Investigator grantee; Léma Massi, Ph.D., a 2014 NARSAD Young Investigator grantee; and Philip Tovote, Ph.D., a 2013 and 2016 NARSAD Young Investigator grantee.