Keeping Fear in Check

Fear, in a nutshell. The balance of oxytocin-sensitive neurons (red) and vasopressin-sensitive neurons (green) in the central nucleus of the amygdala may calibrate fear responses.

If you've ever stepped out on a 10-meter-high diving platform or wandered down a dark alley, you're probably familiar with the racing heart and sweaty palms that characterize the autonomic nervous system's response to fear. Now, researchers have clarified the molecular underpinning of the brain's fear response. The findings may point the way to better drugs for people with phobias and other anxiety disorders.

Fear responses are controlled by an almond-shaped structure called the amygdala, located deep inside the brain. The amygdala weighs messages sent from many regions of the brain, and when things get sufficiently scary, it triggers the autonomic fear response via "output" neurons located in a subdivision called the central amygdala.

In the new study, neuroscientist Daniel Huber at the University of Lausanne, Switzerland, and colleagues used slices of rat brains to take a closer look at the chemical communication signals used by the central amygdala's neurons. They found that vasopressin, a peptide known to boost anxiety and stress, increased the electrical activity of output neurons in one part of the central amygdala, while oxytocin, a peptide with nearly opposite effects on mood, stimulated neurons in an adjacent region. Moreover, neurons stimulated by oxytocin released a neurotransmitter that inhibited the vasopressin-sensitive output neurons.

The findings suggest that vasopressin and oxytocin have contrasting influences on behavior because they have opposite effects on the output neurons of the central amygdala, the team reports in the 8 April issue of Science. The researchers speculate that natural variations in the balance of vasopressin and oxytocin receptors in the central amygdala could explain why some individuals are typically nervous, while others are seemingly immune to anxiety.

The region where the team found the oxytocin neurons acts as an off switch for fear, says Gregory Quirk of Ponce School of Medicine in Puerto Rico. Quirk and others have suggested that drugs that target this area might alleviate anxiety disorders, but so far there haven't been any good candidates. Now, says Quirk, oxytocin could be the "silver bullet" researchers have been looking for.

Related sites
Gregory Quirk's site
Information about anxiety disorders from the National Institute of Mental Health
An article about the amygdala and fear from the Society for Neuroscience