Understanding exactly how our brains detect and respond to such danger has been a goal of Joseph LeDoux of the Center for Neural Science at New York University for much of his career. His pioneering work on “fear conditioning,” which he now calls “threat conditioning,” revealed the neurological pathways through which we react to threats.
This Pavlovian-type conditioning uses a neutral stimulus like an auditory tone at the same time as a painful event, and over time, this tone becomes associated with the discomfort and can trigger a fear response in the brain, specifically the amygdala. The neural processing in the amygdala causes chemical processes in the brain cells that lead to our natural defenses in the face of a threat – whether a spider or a robber.
LeDoux’s work has not only contributed to our understanding of these processes but also to ways we can work to overcome pathological fears, including through work on memory and fear. He will be a keynote speaker at the CNS 20th anniversary meeting in San Francisco this April. He talked with CNS about his research and how it has evolved over the past couple decades.
CNS: How did you first become interested in studying fear? Why is it important to you?
LeDoux: I developed an interest in emotion while doing my Ph.D. research on split-brain patients with Mike Gazzaniga in the mid 1970s. I then decided to turn to animal studies as techniques for studying the human brain were pretty limited at the time. I chose a task that I could use to induce an emotion in rats. The task was “fear conditioning.” But I soon concluded that I was not studying “emotion” but instead one emotion, fear.
But the truth is I have always emphasized that I study how the brain detects and responds to danger (threats) rather than how it feels fear. But most people think I work on “fear” in the sense of feelings. I’ve been trying to clear up that confusion lately. We can study threat processing in rats and people alike, but we have no idea what an animal experiences when threatened.
CNS: You delivered a speech at the 1999 CNS annual meeting. Can you tell us about a couple of the most important changes in our knowledge about the brain mechanisms underlying fear since that talk 13 years ago?
LeDoux: There has been a lot of progress on the details of the circuits and cellular and molecular mechanisms. Research on threat conditioning (what we use to call fear conditioning) is now one of the leading areas for which findings in animals can be comfortably applied to humans.
CNS: Can you give us a preview of what you will be discussing in your keynote address at the CNS annual meeting in San Francisco (April 13-16, 2013)?
LeDoux: I’m going to be talking about the relation between emotion and survival and focusing on this reconceptualization. We have certain survival functions that we share with all animals and even unicelluar organisms to some extent. They contribute to emotions but are not emotional functions. Emotion is what happens when we become consciously aware that this stuff is going on in our brain and body. Every animal has survival functions. Some animals have feelings when these occur. Humans do but its hard to say which other animals, if any, do. But not all emotions are based on survival functions.
An important question is what makes certain states all inhabit some psychological world called fear – whether elicited by a snake at your feet, the concern of of not passing an exam, the thought that death awaits some day, or that God will punish bad behavior. I would say that what makes an emotion an emotion is based on various non-emotional ingredients (activities in the brain and body are interpreted as being relevant to our well-being).
CNS: Does your research speak to why people find fun in fear around Halloween time?
LeDoux: Fear or other emotions are conscious experiences and can involve quite a bit of cognitive interpretation of situations. So we can get the body revved up in a horror movie or haunted house and enjoy the rush since we know there is no consequence to it.
CNS: Can you describe 1 or 2 promising lines of therapy being developed now for treating pathological fear?
LeDoux: Research on threat conditioning has led to a number of potential therapies. One is the use of drugs like d-cycloserine to enhance extinction learning. Mike Davis and Kerry Ressler and their colleagues at Emory have pioneered this work.
Another involves the use of manipulations that alter memory after retrieval. My lab has contributed a lot to this, showing the bodily responses elicited by triggers of aversive memory can be blunted by disrupting the re-storage of the memory after retrieval. This is called reconsolidation blockade. It is being tested now as a treatment for traumatic memory. Ideally, it will blunt the responses (behavioral reactions and autonomic and endocrine responses) controlled by implicit memory associations in the amygdala but leave the explicit declarative memory involving the hippocampus and other cortical areas intact.
CNS: What is the next step for your research? What are you working on now?
LeDoux: We do a lot now on how the brain transitions from reaction to action. You can’t stay frozen in the face of a threat forever. You have to act. Just how the brain switches is fascinating and accounts for a lot of the lab’s work now. This too is important for treatment, as things that help us move from reaction to action – from passive to active coping – can lead to better outcomes in people with anxiety disorders.
Media contact: Lisa M.P. Munoz, CNS Public Information Officer,