|Vol. 18, No. 15||Dec. 17, 1998|
Jeffrey Rosen in the laboratory
Rosen's research, using rodents, is involved in the brain mechanisms of fear, focusing on the amyglada. An almond shaped area, located in the temporal region under the cortex, the amyglada is involved in emotional responses and the expression of fear-related behaviors.
Understanding the role of the amyglada in normal fear response is important as the basis for understanding the neurobiology of pathological fears and anxieties in humans, Rosen said. These can include specific phobias, such as fear of heights; social phobias, such as the fear of interacting with others; and posttraumatic stress, following terrifying or distressful events, he said.
While a graduate student at Wayne State University, Rosen was involved in epilepsy research. "The most common form of epilepsy, temporal lobe epilepsy, involves abnormal activity in the amyglada. It has been discovered that fear is a major component of epilepsy. Not only do people with epilepsy fear seizures, often during and after a seizure, they become frightened by those around them who are trying to help them.
"For extreme cases of epilepsy where a patient has multiple seizures each day and can't be helped by medication, the amyglada is sometimes removed by surgery, and patients without the amyglada become less fearful," he said.
A woman whose amygdala was calcified is being studied extensively by scientists in fear research. Although she can recognize happy and angry faces, she is unable to recognize fearful faces, Rosen said.
Rats with epilepsy have increased fear/startle reactions. Stimulating the amyglada also can induce exaggerated fear-potentiated responses in rodents.
On the other hand, animals without the amygdala no longer have the protective response of fear although they continue to function fairly normally in other ways, he said. When other parts of the brain are excised, fear still exists.
Rosen's work in epilepsy research led to his interest in understanding the brain mechanisms of fear itself and the role of the amygdala. While he did his postdoctoral work at Yale University, the focus of his research broadened and changed from epilepsy to the neurobiology of fear.
Rosen continued his studies in the biological/psychiatry branch of the National Institute of Mental Health, where he headed the neurochemistry and molecular biology unit until he joined the UD faculty in 1995.
According to Rosen, there are stereotypical, limited responses to fear in humans, rodents and most other animals. In the first stages of fear, humans stop and become hyper-vigilant.
"The heart rate slows and muscles tense as a person becomes oriented- discovering what it is that is fearful. When the threat becomes real and possibly injurious, the heart races and stress hormones are released as they deal with the situation," he said.
"Rats are afraid of anything new and can become conditioned to fear things such as a bright light or a tone, accompanied by a mild footshock. After conditioning, when the light or tone is presented alone, they freeze and become immobile. If a loud noise is introduced while the animal is in this state, the animal jumps-known as fear-potentiated startle," Rosen said.
The next stage of fear in rodents changes from freezing to the flight/fight stage. A rodent tries to escape or, if that is not possible, fights. A cornered rat hisses, stands up on its legs and bares its teeth. The heart rate and the stress hormone levels increase at this stage, Rosen said.
Experiments have distinguished between conditioned fear and innate fear, Rosen said. For example, a natural predator of rats is a fox. Although rats used in laboratories have been bred indoors for generations and have never been exposed to the outdoors, when a fox odor is introduced, they freeze. When other foul odors are used, there is no fear-reaction, which indicates that fear of foxes is part of their biological makeup, Rosen said.
Rosen's research centers on investigating the molecular changes that take place in the amyglada as genes and proteins are expressed when animals experience fear from different stimuli.
In a paper on this topic written with colleagues in the field, Rosen stated, "Normal and hyperexcitable mechanisms in amyglada-associated fear circuits delineated in animals may be similar to those mediating fear and anxiety states in humans. Animal studies of hyperexcitability in these brain circuits may thus bring us closer to an understanding of the neurobiology of fear and anxiety."
-Sue Swyers Moncure
Photo by Jack Buxbaum