Some rats are naturally more fearful than others. The neuroscientist’s current research focuses on what these outliers can tell us about the psychopathology of fear in humans.

Question: What are you currently researching?

Joseph LeDoux: I think one of the more interesting things is our focus now on individual differences, you know, if you condition 10 rats or 20 rats to be afraid of the sound paired with a shock you find that some are very afraid and some are not very afraid and the other are kind of in the middle.  So the typical way of dealing with that is you average it altogether and you get the mean, and that’s what you study.  

The outliers are viewed as just kind of a nuisance which adds variance to the data, but now we’ve begun to study those previous nuisances to try to understand a little more about what’s really going on in terms of pathological fear, because almost all of the drugs that are developed to treat fear and anxiety are developed on that average animal, rather than the extremes. But what we really need to understand, I think, and the drugs to be much more effective and perhaps have fewer side effects if they were targeted for the animals with extreme fear.  

So we’re trying to come to the question of what causes animals to have this extreme fear.  What pushes them out to the ends of the distribution?  The basic idea is that, you know, one way to do this is to take animals that have the extreme fear and to start breeding them and create genetic lines that are fearful, but I think it’s also interesting to ask, given that it already exists in the population of rats, these extreme behaviors, what can we learn about, say the pathophysiology of extreme fear by studying those animals.  In other words, we don’t have to start breeding and creating genetic lines to get at what’s different because the difference is already there.

We can compare animals that are really afraid and those that are not afraid and look in their brains and see if there area any, for example, structural differences in the amygdala in terms of how the neurons, what their dendritic branches, what their axons are like.  What kinds of molecules are present in those neurons?  And to what extent?  So we can get a lot of information that might distinguish fearful and not so fearful rats that could provide important clues as to what pushes them out there towards the extremes.  

But that project is just beginning so we don’t have any answers, but I think it’s going to be an important project.

Recorded on September 16, 2010
Interviewed by Max Miller