How the brain suppresses fear: mouse study offers path to anxiety treatments

Two brain regions work together when mice learn to override the instinct to run and hide from a potential threat

Mice immediately bolt for shelter when they see the looming shadow of a bird, just as humans jump when they see a spider. But these instinctive reactions, which are controlled by the brainstem, can be suppressed if animals learn that a scary stimulus is harmless.

In Science today, neuroscientists reveal the precise regions of the brain that suppress fear responses in mice¹ — a finding that might help scientists to develop strategies for treating post-traumatic stress disorder and anxiety in people.

The study showed that two parts of the brain work together to learn to suppress fear. But, surprisingly, only one of these regions is involved in later recalling the learnt behaviour. “This is the first evidence of that mechanism,” says neuroscientist Pascal Carrive at the University of New South Wales in Sydney, Australia.

In the study, an expanding dark circle was used to imitate a swooping bird, and caused naive mice to run to a shelter. To teach the mice that this looming stimulus was not dangerous, a barrier was added to prevent the animals from hiding.

“I like their behavioural model,” says Christina Perry, a behavioural neuroscientist at Macquarie University in Sydney. “It’s very simple,” she adds. The mice “don’t get eaten, so they learn that this fake predator is not, in fact, a threat”.

As the mice were learning to be bolder, the researchers switched specific types of neurons on or off using optogenetics — a well-established technique that allows neurons to be controlled with light.

When researchers silenced the parts of the cerebral cortex that analyse visual stimuli (called the posterolateral higher visual areas), the mice did not learn to suppress fear and continued to try to escape from the fake bird — suggesting that this area of the brain is necessary for learning to suppress this fear reaction.

‘Unexpected’ result

However, mice already trained to overcome their fear could still enact the new, courageous behaviour when the posterolateral higher visual areas were switched off. This is because the memory was stored in a region near the centre of the brain called the ventrolateral geniculate nucleus, “an area of the brain that can inhibit others; it’s quite a strong control region”, says co-author Sonja Hofer, a systems neuroscientist at University College London (UCL).