The wise words of Cartman
Dr. Rafael M Yuste presented the opening lecture this year at the 2013 Psychiatry Grand Rounds at Columbia University. It was a great talk delivered by my PI and I have written up my take on the talk.
BRAIN Initiative Project: Relevance for Psychiatry
Dr. Yuste, or Rafa as we often call him in lab, was originally not a neuroscientist but a licensed physician in Europe. He hasn’t had a patient in 26 years. Long ago in his early days as a psychiatrist in Spain, he interviewed paranoid schizophrenia patients.
Paranoid schizophrenia is a lifelong condition in which a person loses touch with reality. Classic symptoms include delusions and hearing things that are not real. It is a condition that can ultimately lead to suicidal behaviour.
Yuste, perplexed by these patients, felt helpless. He described these patients as some of the most brilliant people he had met and described it as though “a switch that had been turned all the way to the right needed to be flicked all the way to the left.”
To treat mental illnesses such as paranoid schizophrenia, we need to determine the pathophysiology of the disease. Or as Yuste would say, we have to build the according cortical circuit. Most of these mental illnesses are typically characterized by lesions in the cortex, which is what most likely leads to a deficit in standard function.
The cerebral cortex is one of the most important regions of the mammalian brain and largely consists of pyramidal neurons, which I’ll describe more in depth in a later post.
In order to help these paranoid schizophrenia patients, Yuste felt it was best to conduct neuroscience research to better understand the brain. He left his native country and came to the United States to pursue a PhD degree at the Rockefeller Institute in NY under Dr. Sydney Brenner.
Yuste has conducted research on imaging the brain and has helped advance the techniques of two-photon excitation microscopy and optical imaging using a wide range of compounds. Optical imaging systems are unique in that it involves microscopy of living animals as opposed to fixed tissues.
And so let’s fast forward to today. We have previously studied the brain by examining individual nerve cells or neurons. However, this isn’t the answer according to Yuste. He had a great analogy to the study of the brain. He asked the audience to imagine they were UFOs that had just landed on the Empire State building. And in your life as a UFO, your goal is to determine the function of the Empire State. With great scrutinization, you’ve found that the Empire State is composed of atoms. Well… now what? You still don’t know the role of the Empire State.
The purpose of this analogy is to point out how important it is we look at emergent properties when conducting research. To determine the function of the Empire State, you need a floor plan. And to determine the function of the human brain, you need that same “floor plan” or a circuit.
Palisades of neurons cover the brain in every nook and cranny. Yuste quickly characterized such neurons in order of increasing complexity as:
Molecules -> Synapses -> Cellular -> Circuits -> Systems
We know that diseases can occur at every single one of these levels, and so there are several emergent diseases of the brain. What we do not know is at which of these levels do diseases like paranoid schizophrenia occur for sure.
With great effort from neuroscientists, nanoscientists and physicists from all around the world, perhaps the BRAIN Initiative will truly one day be a reality.