Why a Neural Circuit for Fear Matters

At the end of anxiety, the paraventricular nucleus of the thalamus.

Image: Bo Li/Cold Spring Lab

In the pantheon of feels, fear is something truly special. Is there anything more motivating than abject dread? Anything more paralyzing than full-on terror? Fear is not something to be fucked with, and that fact is deeper than anything else.

It makes sense then that the brain has its very own fear neural-circuitry. This is the revelation, anyhow, of a stu​dy out this week in the journal Nature: fear is located and stored within a distinct region of the brain. Fear has a home.

It's hardly a trivial finding: anxiety and panic disorders, which might be understood as overexpressions of fear or fear hyperactivity, ruin lives. Currently, it's possible to tame anxiety / panic—sometimes—but nothing like a cure exists, just approximations.

It's not that fear has been a total mystery to neuroscientists. The team behind the current study, led by Cold Spring Harbor Laboratory professor Bo Li, had previously shown that fear learning is orchestrated by neurons within the central amygdala, the region of the brain responsible for emotions and memory. The question of what exactly directs the amygdala, how "fear" is delivered as a raw material, remains open.

A likely candidate for "fear conditioning" is the paraventricular nucleus of the thalamus (PVT), a region of the brain activated by physical and psychological stress. The problem has been in finding a link between the PVT and amygdala. This is what the new study shows: how the PVT, which might be viewed as the brain's stress sensor, interfaces with the amygdala to produce what we experience as fear.

In other words, Li and his team made fearless mice

The study's first portion basically just took some mice and flipped their PVT zones on and off. Inactivation resulted in the prevention of, "fear conditioning, an effect that can be accounted for by an impairment in fear-conditioning-induced synaptic potentiation." In other words, Li and his team made fearless mice. Likewise, boosting PVT activity correlated with an increase in patterns associated with fear conditioning.

Using data collected from PTSD patients, the researchers were able to isolate a likely chemical mediator of the PVT-amygdala, known as brain-derived neurotrophic factor or BDNF. This is the stuff that tells the amygdala to get to work structuring and storing fear memories. More properly, it affects neuroplasticity, a broad concept describing how the brain is able to reshape itself on a variety of levels in response to behavior, environmental factors, emotions, neural processes, and physical injury.

Using dyes and more mouse brains, Li and his team were able to trace the expression of BDNF by PTV neurons and the subsequent neural activation back in the amygdala. Limiting this expression limited fear conditioning/learning, and, likewise, boosting it resulted in fearful responses in mice that hadn't experienced an actual IRL fear stimulus.

The identification of this PVT-amygdala-BDNF is hardly trivial, offering another, better target for future anxiety/panic disorder therapies. "Our work provides mechanistic insight into a novel circuit that controls fear in the brain, and provides a target for the future treatment of anxiety disorders," Li said in a statement.

By the way: anxiety.

As a postscript: anxiety sucks. It much more than sucks.

It's pretty common—in my experience—for people to confuse anxiety and anxiety disorder, which is really a problem of nomenclature. Anxiety as everyday stress and worry is an uncomfortable buzzing, while the disorder is a full-on roar. It's all-consuming.

The difference might be classified in terms of fear, where the advance scouts of fear (again: worry, stress, nerves) give way to the advancing battalions of terror. Pure, undiluted fear. It's hard to explain it really; by the 10th or 11th emergency room doctor it's not even much easier. It is an upwelling, a geyser, of fear—think of the feeling just before waking from your worst dream ever—that doesn't go away.

Fear is natural. It protects us and has done so for a very, very long time. None of us, as individuals or as a species, would have gotten very far without it. But it also destroys lives, keeping people from social relationships and jobs and even fresh air. It seems now that fear has an answer.