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Turning off this newly discovered brain pathway could help us block fearful memories

Next step could be learning to erase fearful memories

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lab mouse — George Shuklin/ Wikimedia commons

Scientists now know how to make you forget your fears — at least if you’re a mouse. By turning off a newly discovered brain pathway, scientists were able to make mice lose their fear of a shock. It’s early research, but it may point toward methods that could help people with anxiety and PTSD.

After finding a new pathway in the brain important for creating fearful memories, scientists trained mice to fear a high-pitched tone by shocking the rodents every time they heard it, according to a study published today in Nature Neuroscience. They waited until the rodents would freeze in fear even without the shock before proceeding to the next stage: viewing the mouse brains. Using a specialized microscopy technique, the scientists observed that there was growth in the neurons along that pathway. So what would happen if they could turn that pathway off?

If we can reduce fear response in mice, maybe we can reduce it in humans too

Being able to feel fear is crucial to survival; it teaches us to become more careful in dangerous situations. But many people’s fear systems are too efficient. They feel a lot of fear even when there’s nothing to be afraid of, and this leads to anxiety disorder  — which 18 percent of Americans have — and PTSD, which 8 percent of Americans will experience at some point.

Think about the brain like a series of roads. We used to think that fear was a single one-way street that started at the part of the brain charged with interpreting sound — the auditory cortex — and ended at a place that processes emotion, called the lateral amygdala. But today’s study suggests that for us to truly feel fear, the information also needs to travel up a different one-way street, from the amygdala all the way back to the auditory cortex. By cutting off this second one-way street, we can prevent mice from feeling fear. “If we can reduce the fear response in mice, hopefully this will help us find some way to reduce this in humans too,” says Yang Yang, a researcher at the Chinese Academy of Sciences who led today’s study.

Yang started to suspect there might be a different fear pathway years ago when looking at an extremely detailed map of the brain called the Allen Brain Atlas. Using a tracer, she found that she was right. There were a lot of axons — the part of the neuron that sends information to other neurons — sending information from the lateral amygdala to the auditory cortex. This was “very surprising” since Yang had read reviews claiming this pathway didn’t exist in rodents.

The next step is learning to erase the memories themselves.

Finding a new pathway doesn’t mean much on its own. The team needed to prove that it played a role in regulating fear memories. So after teaching mice to fear the sound, the team viewed the synapses — or connections between neurons — along this new pathway. When a memory is formed, connections between axons and dendrites grow. Animals conditioned to fear the sound had bigger connections in the new pathway, confirming Yang’s theory.

To go one step further, the team used two methods to turn the pathway off. In one, they used light to shut down the connections along the pathway, using a technique called optogenetics. In the second, they achieved the same effect with a virus containing a receptor called hM4D. With the pathway off, the mice lost their fear entirely. “I didn’t expect there to be such a strong effect, and we used both methods because we wanted to make sure that the response was real,” says Yang.

Mice and humans are thankfully not the same, but these findings do bring us a little closer to understanding how a similar pathway in our brains might work. Mice learn the most through hearing, so it makes sense that this connection exists from the lateral amygdala to the part of the brain that processes sound. We’re more visual than rats, though, and anatomical studies in monkeys show that they have pathways from the lateral amygdala to the visual cortex. No studies yet have investigated how this pathway works. “I think the function of this pathway in mice suggests that an equivalent in the visual cortex of monkeys might have a similar function, and that inhibiting the pathways could help treat these issues,” says Yang.

This “really compelling” finding is “especially impressive because they actually were able to shift behavior in an input-specific way,” says Kay Tye, a neuroscientist at the Massachusetts Institute of Technology. Knowing this could help us develop more useful treatments, Tye adds. For example, a therapy called transcranial direct-current stimulation (or tCDS) works by sending currents from electrodes placed on the scalp to specific areas of the brain. This treatment can only reach areas near the surface of the brain, and the amygdala is deeper inside. But the auditory cortex is closer to the surface and so more research into its specific role in fear processing could make tCDS and similar treatments more useful.

Unfortunately, shutting off the pathway only blocked the memories temporarily. It didn’t delete them, and they could be accessed later. The next step for Yang’s team is one familiar to everyone who’s seen Eternal Sunshine: erasing the memories themselves.