Full text of neurobiologist David Anderson’s talk: Drugs, dopamine and drosophila — A fly model for ADHD? at TEDxCaltech conference.
Listen to MP3 Audio here:
David Anderson – Seymour Benzer Professor of Biology at Caltech
Hi, I would like to thank everybody first, who came down here to learn that Caltech is about more than rocket science and earthquakes. It’s not that JPL and rocket science and space exploration aren’t great. But those of us who are neuroscientists here know that the brain is the final frontier.
So, raise your hand if you know someone in your immediate family or circle of friends who suffers from some form of mental illness. I thought so, not surprised.
And raise your hand if you think that basic research on fruit flies has anything to do with understanding mental illness in humans. Yeah, I thought so I’m also not surprised. I can see I got my work cut out for me here.
As we heard from Dr. Insel this morning, psychiatric disorders like autism, depression and schizophrenia take a terrible toll on human suffering. We know much less about their treatment, and the understanding of their basic mechanisms than we do about diseases in the body.
Think about it. In 2013, the second decade of the millennium, if you’re concerned about a cancer diagnosis, and you go to your doctor, you get bone scans, biopsies and blood tests.
In 2013, if you’re concerned about a depression diagnosis, you go to your doctor and what do you get? A questionnaire. Part of the reason for this is that we have an oversimplified and increasingly outmoded view of the biological basis of psychiatric disorders. We tend to view them and the popular press aids and abets this view as chemical imbalances in the brain, as if the brain were some kind of bag of chemical soup full of dopamine, serotonin and norepinephrine.
This view is conditioned by the fact that many of the drugs that are prescribed to treat these disorders like Prozac act by globally changing brain chemistry, as if the brain were indeed a bag of chemical soup. But that can’t be the answer because these drugs actually don’t work all that well.
A lot of people won’t take them or stop taking them because of their unpleasant side effects. These drugs have so many side effects, because using them to treat a complex psychiatric disorder is a bit like trying to change your engine oil by opening a can and pouring it all over the engine block. Some of it will dribble into the right place, but a lot of will do more harm than good.
Now, an emerging view that you also heard about from Dr. Insel this morning, is that psychiatric disorders are actually disturbances of neural circuits that mediate emotion, mood and effect. When we think about cognition, we analogize the brain to a computer, that’s no problem.
Well, it turns out that the computer analogy is just as valid for emotion, it’s just that we don’t tend to think about it that way. But we know much less about the circuit basis of psychiatric disorders, because of the overwhelming dominance of this chemical imbalance hypothesis.
Now, it’s not that chemicals are not important in psychiatric disorders, it’s just that they don’t bave the brain like soup. Rather, they’re released in very specific locations, and they act on specific synapses to change the flow of information in the brain.
So, if we ever really want to understand the biological basis of psychiatric disorders, we need to pinpoint these locations in the brain where these chemicals act. Otherwise, we’re going to keep pouring oil all over our mental engines, and suffering the consequences.
Now to begin to overcome our ignorance of the role of brain chemistry and brain circuitry, it’s helpful to work on what we biologists call model organisms, animals like fruit flies, and laboratory mice in which we can apply powerful genetic techniques to molecularly identify and pinpoint specific classes of neurons, as you heard about in Allan Jones’s talk this morning.
Moreover, once we can do that, we can actually activate specific neurons, or we can destroy or inhibit the activity of those neurons. So, if we inhibit a particular type of neuron, and we find that a behaviour is blocked, we can conclude that those neurons are necessary for that behaviour.
On the other hand, if we activate a group of neurons, and we find that that produces the behavior, we can conclude that those neurons are sufficient for the behavior. So, in this way, by doing this kind of test, we can draw cause and effect relationships between the activity specific neurons in particular circuits and particular behaviors, something that is extremely difficult if not impossible to do right now in humans.
But can an organism like a fruit fly, which is it’s a great model organism? Because it’s got a small brain. It’s capable of complex and sophisticated behaviors. It breeds quickly, and it’s cheap. But can an organism like this teach us anything about emotion like states? Do these organisms even have emotion like states? Or are they just little digital robots?
Charles Darwin believed that insects have emotion and express them in their behaviors as he wrote in his 1872 monograph, on the expression of the emotions in man and animals. And my eponymous colleague Seymour Benzer believed that as well. Seymour is the man that introduced the use of Drosophila here at Caltech in the 60s, as a model organism to study the connection between genes and behavior.
Seymour recruited me to Caltech in the late 1980s. He was my Jedi and my Rabbi while he was here and Seymour taught me both to love flies, and also to play with science.
So how do we, how do we ask this question? It’s one thing to believe that flies have emotion like states, but how do we actually find out whether that’s true or not?
Now, in humans, we often infer emotional states, as you’ll hear later today, from facial expressions. However, it’s a little difficult to do that in fruit flies. It’s kind of like landing on Mars, and looking out the window of your spaceship at all the little green men who are surrounding it, and trying to figure out how do I find out if they have emotions or not? What can we do? It’s not so easy.
Well, one of the ways that we can start is to try to come up with some general characteristics or properties of emotion like states, such as arousal, and see if we can identify any fly behaviors that might exhibit some of those properties. So, three important ones that I can think of are persistence, gradations in intensity, and valence.
Persistence means long lasting; we all know that the stimulus that triggers an emotion causes that emotion to last long after the stimulus is gone. Gradations of intensity mean what it sounds like, you can dial up the intensity, or dial down the intensity of an emotion.
If you’re a little bit unhappy, the corners of your mouth turned down and you sniffle, and if you’re very unhappy, tears pour down your face, and you might sob.
Valence means good or bad, positive or negative. So, we decided to see if flies could be provoked into showing the kind of behaviour that you see by the proverbial wasp at the picnic table, you know, the one that keeps coming back to your hamburger, the more vigorously you try to swat it away, and seems to keep getting irritated.
So, we built a device, which we call a puffle mat, in which we could deliver little brief air puffs to fruit flies in these plastic tubes in our laboratory bench and blow them away.