Freeze or run? Not that simple

Fear can make you run or fight, or it can glue you to the spot. Now, scientists have identified the part of the brain and the type of neurons that determine how mice react to a frightening stimulus.

The scientists, from the European Molecular Biology Laboratory (EMBL) in Monterotondo, Italy, and GlaxoSmithKline in Verona, Italy, combined pharmaceutical and genetic approaches with functional MRI in mice. Their findings show that deciding whether or not to freeze to fear is a more complex task for our brains than previously realized.

The scientists turned off a set of neurons (type I cells) in the amygdala, which was known to be involved in responses to fear. To measure fear, the scientists trained the mice to associate a sound with an unpleasant shock: when the mice heard the sound, they would freeze in fear.

‘When we inhibited these neurons, I was not surprised to see that the mice stopped freezing because that is what the amygdala was thought to do. But we were very surprised when they did a lot of other things instead, like rearing and other risk-assessment behaviours,’ says Cornelius Gross, who led the research at EMBL.

‘It seemed that we were not blocking the fear, but just changing their responses from a passive to an active coping strategy. That is not at all what this part of the amygdala was thought to do.’

To find out what other parts of the brain were involved in these responses, the scientists used a magnetic resonance brain-scanning technique developed for use in mice by Angelo Bifone’s team at GSK. Surprisingly, they found that the switch from passive to active fear was accompanied by the activation of large parts of the cortex and that blocking this activation with the drug atropine could reinstate freezing behaviour and flip back the fear switch.

Before the study, the amygdala was thought to control fear via the brain stem – not the cortex.

Humans also show freezing and risk-assessment behaviours in response to fear. Understanding how to switch from passive to more active fear coping strategies might be helpful for us in adapting to the stress and unpredictability of modern life, the scientists suggest.

Further reading

Gozzi, A. et al. (2010) A neural switch for active and passive fear. Neuron 67, 656–666

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