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The journey begins when a rat (we'll get to humans later) feels the stress, in this case an electric shock. The rat's senses immediately send a message to the central portion of its brain, where the stimulus activates two neural pathways. One of these pathways is a relatively long, circuitous route through the cortex, where the brain does its most elaborate and accurate processing of information. The other route is a kind of emergency shortcut that quickly reaches an almond-shaped cluster of cells called the amygdala.
What's special about the amygdala is that it can quickly activate just about every system in the body to fight like the devil or run like crazy. It's not designed to be accurate, just fast. If you have ever gone hiking and been startled by a snake that turned out to be a stick, you can thank your amygdala. Joseph LeDoux, a neuroscientist at New York University, calls it "the hub in a wheel of fear."
But while the amygdala is busy telling the body what to do, it also fires up a nearby curved cluster of neurons called the hippocampus. (A 16th century anatomist named it after the Greek word for seahorse.) The job of the hippocampus is to help the brain learn and form new memories. And not just any memories. The hippocampus allows a rat to remember where it was when it got shocked and what was going on around it at the time. Such contextual learning helps the poor rodent avoid dangerous places in the future. It probably also helps it recognize what situations are likely to be relatively safe.
By this point, the other half of the stress signal has reached the cortex, which confirms that there's a danger present and figures out that it's causing pain. Once the shock has warn off, a part of the brain called the prefrontal cortex sends out an all-clear message and lets the amygdala know that it's O.K. to stand down. At least it's supposed to. It seems that it's harder to turn off a stress response than to turn it on. This makes sense, in terms of survival. After all, it's better to panic unnecessarily than to be too relaxed in the face of life-threatening danger.
Discovering this basic neural circuitry turned out to be a key breakthrough in understanding anxiety. It showed that the anxiety response isn't necessarily caused by an external threat; rather, it may be traced to a breakdown in the mechanism that signals the brain to stop responding. Just as a car can go out of control due to either a stuck accelerator or failed brakes, it's not always clear which part of the brain is at fault. It may turn out that some anxiety disorders are caused by an overactive amygdala (the accelerator) while others are caused by an underactive prefrontal cortex (call it the brake).
It may also be that an entirely different part of the brain holds the key to understanding anxiety. Michael Davis, a behavioral neuroscientist at Emory University in Atlanta, has spent six years studying a pea-size knot of neurons located near the amygdala with an impossible name: the bed nucleus of the stria terminalis, or BNST. Rats whose BNST has been injected with stress hormones are much jumpier than those that have got a shot in their amygdala. Could the BNST be at the root of all anxiety disorders? The clues are intriguing, but as scientists are so fond of saying, more research is needed.