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What could we do without fear? I, for one, could interface with more than one other human simultaneously without drinking all of the alcohol. That would be OK. I might be a better rock climber, though I might also be a more reckless, dangerous rock climber. I guess it would really be a big package deal, where fear and its anxiety kin just stop making sense. A lot of things would be more boring, I think.

This isn't strictly a theoretical idea. In a famous case, a patient known as SM has managed to live most of her life with no fear thanks to a rare calcification of her amygdala, the region of the brain most associated with the emotion. Her actual identity is closely guarded, but NPR's Invisibilia managed a rare interview with her in an episode last season. It's worth listening to.

That episode is why some research published today in Nature Neuroscience especially caught my eye. It describes a "new pathway for fear." Neuroscientists have some understanding of the routes leading from the various sensory organs that converge in the amygdala, but less so about those running in the opposite direction. In other words, we know how information makes it from the outside world to the formation of fear-memories, but not so much how those fear-memories are accessed again as, well, fear.

The new paper describes an opposing pathway running from the lateral amygdala (LA) to the auditory cortex (ACx), which was discovered by the researchers using electron microscopy and fear conditioning in mice. The circuit appears to have a role in the process of expressing learned defensive responses to sounds. We have fear-sounds, integrated into fear-memories, and we have learned defensive reactions to these sounds. This is where all of that comes from.

(In the experiments, mice are trained to associate pain the form of foot shocks with specific sounds. During this fear conditioning, observations are made of any synaptic changes that occur during the conditioning.)

The group behind the new paper, a large team based at the Shanghai Institutes for Biological Sciences, further explored this using mice who had had their LA to ACx circuit limited either chemically or by using optogenetics (where light is able to control various brain functions via cells genetically-engineered to respond to it).

"To determine the function of this previously uncharacterized LA?ACx pathway, the authors trained mice with auditory fear conditioning," explains Bo Li, a neuroscientist at Cold Spring Harbor Laboratory, in a separate Nature Neuroscience commentary. "After the training, normal mice would freeze in response to the sound. However, in mice in which the LA?ACx pathway was specifically inhibited by either chemogenetics or optogenetics during the memory recall test, sound no longer induced freezing. In other words, the LA?ACx pathway is necessary for the recall of the aversive memory."

What's weird is that this doesn't seem to work in the other direction. If you block the pathway leading from the auditory cortex to the amygdala, fear-inputs still manage to get through and form fear-memories. We're really just now starting to get a handle on all of this.

In any case, it at least seems very likely that we will eventually be able to manipulate our fear machinery in useful ways. But SM, the fearless patient, is also an illustration of what fear even is. For one thing, as one of the many doctors studying her, the University of Iowa's Daniel Tranel, told NPR's Science Friday in 2010, fear is not the same as worry. And, thus, it is not necessarily the same thing as anxiety.

"There's a very fundamental difference between fear and worry, and she does worry," Tranel explained. "Worry is more in the domain of anxiety and has a lot to do with something we humans do a lot of, which is the future, spending time in the future." And the future, it seems, is something we're stuck with.

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