The Nucleus of Phobias

In frightening situations, behavior is directed from deep within the brain by the amygdala. Now a study published in this week's Nature shows that this almond-sized structure orchestrates two different types of fear response: a Pavlovian, reflexive reaction--like startling upon the sight of a snake--and a voluntary choice to avoid unseen, possible danger--such as shunning a sinister neighborhood. The finding suggests a region in the amygdala called the basolateral nucleus may play a much more important role in phobias than was previously thought.

For their experiments, psychologists Barry Everitt, Simon Killcross, and Trevor Robbins of the University of Cambridge, U.K., used neurotoxins to destroy either the central or basolateral nuclei of the amygdalas of rats. These animals, as well as controls that had undergone the same operation but without a toxic injection, were then taught to press two identical levers to obtain food. At unpredictable moments, one of the levers also produced a sound or light stimulus, followed by an electric shock.

After a while the control rats showed classic Pavlovian conditioning: they stopped pressing the "dangerous" lever as soon as the light or the tone came on. In addition, they voluntarily chose to avoid this lever altogether and favor the safe one--even without the stimulus. The lesioned animals did not show both responses. Rats with a damaged central nucleus avoided the nasty lever when there was no warning signal, but were unable to acquire the Pavlovian, reflexive action. In contrast, rats that had their basolateral nucleus wrecked reacted in the Pavlovian manner when the sound or the light came on, but were impaired in their voluntary avoidance behavior.

Most scientists have assumed that the central nucleus orchestrated the fear response, because it connects to the hypothalamus and the brain stem--areas that can get hearts racing and hormones like adrenaline whirling. This finding fits that picture, but it also shows, says Everitt, that the basolateral nucleus has its own way of organizing a fear response--and the neural wiring to go with it. "It's a new role for this nucleus," says Everitt, who suspects the nucleus' connections to the ventral striatum and the prefrontal cortex take care of the voluntary response.

Joseph LeDoux, an expert on brain function and emotion at New York University, likes the work, but cautions that rats in this study may be unusual: "They're dealing with a more complicated form of learning," he says, "so the relevance to our understanding of the amygdala is not so straightforward." If the researchers are right, however, future treatments of anxiety disorders should perhaps target the basolateral nucleus. Based upon the study, says Everitt, that brain area is likely to cause the endless rituals phobic people perform to avoid their object of fear.