The sun was beginning to rise in California’s San Fernando Valley on January 17, 1994, when the ground shook violently, rousing Michael Fanselow, Ph.D., from his sleep with his heart racing.
“I lived at the epicenter of the Northridge earthquake…it was a frightening experience,” the AAAS Member says. “But what happened is basically the thing we study in the lab, which is fear conditioning. Anything like a little vibration or something like a rumble sets me off for a strong response.”
That quickened pulse, sweaty palms, need to run or fight – these are the things Fanselow and members of the Fanselow Research Lab at the University of California, Los Angeles explore. More specifically, their research concerns the nature and function of fear, how it is learned and how fear memories are stored in the brain and can be translated into specific protective behavior patterns. They also study how these normally adaptive reactions can go awry and lead to disorders such as posttraumatic stress disorder (PTSD).
Using rat and mouse models, Fanselow’s lab uses invasive techniques, genetic modifications and electric shocks as a way of understanding how the human brain responds to different levels of stress and how that affects the quality of human life. Their work concentrates on the forebrain regions such as the amygdala, hippocampus and neocortex.
“What the amygdala does is it stores the emotional importance of the experience, but other parts of the brain, like the hippocampus, will provide the memory for all the things that are happening in the context of the situation,” Fanselow explains.
Fanselow was attracted to the study of fear while taking psychology courses as an undergraduate student. The idea that experiences can physically change the brain and lead to something as emotionally powerful as fear piqued his interest.
Stressful situations can alter a person’s behavior physically by impacting the way their brain reacts. To understand this response, Fanselow developed a model using fear conditioning procedures to examine how exposure to a traumatic stressor can affect future reactions.
Rats in an experiment were given 15 electric shocks randomly over the course of 90 minutes. Another set of rats were given only one shock. Compared to the set of rats that only received one shock, the rats that were shocked 15 times displayed an enhanced fear response. Subsequent shocks to the set of rats that were exposed to multiple shocks triggered a reaction in the animals similar to what happens to humans when they respond to stimuli in certain contexts that might lead to an anxiety or panic attack.
“The way we get rid of fear is by exposing the person to stimuli and that exposure produces what we call the extinction of the memory,” he explains. One example of this behavior therapy is using virtual reality to create audiences for people with a public speaking phobia. This kind of exposure therapy has been found to be effective in some fear induced responses like anxiety. “However, the extinction of the memory is not that we lose the old fear memory,” Fanselow clarifies. “It is that we give the brain a second memory that this stimulus is not dangerous.”
The fact that the original fear is not erased is one of the limitations to exposure therapy. This prompted Fanselow to explore other treatments like manipulating the hippocampus with low doses of a drug called scopolamine in rats. The addition of the drug given during the therapy helped generalize the safe memory to other situations.
“Then we went and tried this in people who had public speaking phobias,” Fanselow says. “We made them give speeches in public to extinguish the fear, but there were people who were put in virtual reality environments and told to give these lectures to a particular audience. When we moved them to a different place, the fear returned, so we gave them the same drug we gave to the rats during exposure therapy [in our previous experiments] and we found that it reduced the tendency for the fear memory to come back.”
Inappropriate fear responses in humans can result in the development of anxiety and stress disorders, including PTSD. According to Fanselow, patients with PTSD lose normal daily functioning because these responses become dysfunctional and exaggerated by occurring in situations that do not demand such intense reactions. This can negatively impact their quality of life.
“PTSD is unique among the anxiety disorders in that it is very resistant to exposure,” he says. “Because a part of it is a breakdown in this fear system, you kind of have an impaired ability to learn that the situation is safe and that makes it much more difficult to treat.”
While Fanselow and his lab members have made progress in learning some of the ways trauma can change the brain, moving forward, they are trying to find new approaches to bring the brain back to its natural adaptive state. A lot has changed since Fanselow first published his paper on fear in 1979 thanks to improved medical technology.
“We are getting a much deeper understanding of brain mechanisms,” Fanselow notes. “The original work I was doing [over 40 years ago] was very strictly behavioral. We weren’t really peering into or manipulating the brain. Now we can visualize what neurons are active by examining how they express certain genes. Or we can make mutations in specific neurons to tell us how they function.”