In order to discuss the neuroscience of schizophrenia, we'll need to start by talking a bit about some of the basic landmarks, structural landmarks of the brain. And talk a little bit as well about some of the chemicals of the brain, and how they operate. The brain consists of over 100 billion neurons, so it has many, many individual cells. And these neurons all have a pretty similar structure. They may differ in size, a little bit in shape, but there's sort of a basic architecture that goes along with each of these cells. This architecture consists of a receiving portion of the cell, which is known as the dendrites, or the dendritic tree. It's known as the dendritic tree because it looks sort of like a large tree consisting of many branches. This aspect of the cell collects information from cells next to it, and transfers that information down into the cell body of the neuron, and then what is called the axon of the neuron. The axon of the neuron is a structure within the neuron that transmits a signal electrically, there's an electrical transmission of the signal. That electrical transmission of the signal transfers down the axon, and releases when it terminates at the end of the neuron, a series of vesicles in which a substance called a neurotransmitter is released into a space outside the cell known as the synapse. So just to review again, we have the dendrites which are located at the receiving end of the cell. They receive information, typically in the form of neurochemical signals from other cells. They transfer those signals electrically within the cell down this long portion of the cell known as the axon. And in turn, the axon releases vesicles, which dump neurochemicals into a space outside the cell known as the synapse. That's the key mechanism by which one cell talks to another cell. In addition, these 100 billion neurons that I've talked about, we also have these larger structures that these neurons create. And in the human brain, these larger structures can be broken up into a variety of lobes in the brain. These are sort of areas of the brain that cover on the outside or surface of the brain. If you look at the figure you can see that there are in fact four major lobes in the brain. There is the frontal lobe, which is located at the front of the head, as you would imagine. There is the parietal lobe, which is located just behind the frontal lobe. There are the temporal lobes, which are located on the sides of the brain, and right near the temporal area around the ears. And then we have the occipital lobe, which is located in the very back of the brain. These four lobes are the major structures that make up what we call the neocortex, which is that area of the brain which covers a series of sub-cortical structures. The frontal lobe is thought to be involved in functions such as working memory, attention. Parietal lobe is thought to be involved in functions such as processing the spatial environment in which we're in. The temporal lobes have been implicated in memory, as well as understanding language, and auditory information. And the occipital lobes have been implicated in the processing of vision. In addition to these major neocortical structures, these four lobes, we have sub-cortical structures, which are also very important in the functioning of the brain, and will also be very important in our understanding of schizophrenia. They include the brain stem, which includes structures such as the medulla, involved in breathing. The cerebellum involved in movement. And the pons, which is involved in movement, but also there is a large switching station in the brain connecting one region of the brain to another. There is the midbrain, which consist of aseries of bundles of neurons that we will be talking about with some degree of specificity, with respect to a neurotransmitter called dopamine. And then there are other subcortical structures known as the amygdala, which is involved in emotion. The hippocampus, which is involved in memory And then what are called the basal ganglia, which are involved in the initiation and modification of movement. These are the major structures that we'll be talking about with respect to schizophrenia. So when we think about the neuroscience of schizophrenia, and we think about some of the really key findings that stimulated the emergence of our understanding of schizophrenia, we really have to go back to the discoveries. The French naval surgeon, by the name of Henre Laborit. Laborit was a surgeon who was involved in trying to experiment with new surgical techniques. And he found that using these techniques on humans, that it was not unusual that they would go into a shock reaction. The shock reaction consisted of decreases in heart rate, decreases in blood pressure, decreases in blood to the extremities, and in some cases, during surgery this patients could pass away. As a result of this, Laborit was very interested in developing drugs that would fight this type of shock reaction, that he observed during his surgery. And he experimented with a variety of different types of medications. One of these medications that he experimented with turned out that it wasn't quite so effective at decreasing the shock reaction, but interestingly, it made his patients very quiet and relaxed. Laborit, as a result of this finding, this sort of incidental finding, thought that perhaps this sort of quiet, relaxed feeling that this drug seemed to produce, might be helpful for agitated people who might be suffering with the symptoms of psychosis. People who might have schizophrenia. This was in the 1950s, and Labaright had friends who were psychiatrists. And at St. Anne's Hospital in Paris, he collaborated with two researchers, Denicker and Delay. And Denicker and Delay ran the first studies, in people with psychiatric illness. Using this drug, which was labeled chlorpromazine, one of the anti-psychotic medications. And found that in fact the administration of this drug to their clients, decreased their symptoms. They became less agitated, they were easier to manage in the hospital, and they were very excited about these findings, because at that time there really was not affect, any type of effective treatment for people with schizophrenia and other psychosis. As a result of these findings, these drugs began to be used in a much more frequent way. And they became really, to this day they are considered to be sort of the front line treatment for people with schizophrenia. Laborit who's sort of an interesting character in the history of treatment of schizophrenia, was an actor and a writer as well. And for those of you who may be familiar with the French filmmaker, Alain Resnais, Mon oncle deAmerique, which is a very famous French film came out in 1980. Was actually based on the writings of Laborit, so in addition to discovering the first drug treatment for people with schizophrenia, he also was a writer whose work influenced some major filmmakers. And he actually acted in that movie as well. With this finding of these first anti-psychotic medications, this is a very powerful finding in sort of the history of our understanding of the neuroscience of schizophrenia. These drugs were found to block dopamine receptors. And dopamine is one of about 20 or more neurotransmitters in the brain. Dopamine was discovered in the 1960s, and it is a molecule that communicates information from one neuron to another. It's usually inhibitory in nature. And it's found throughout the brain. It's found in many, many different regions of the brain. Because of the effectiveness of these anti-psychotic medications, which block dopamine in the brain, the first theory that arose to understand the neuroscience of schizophrenia, was the theory of the dopamine. We're going to call this the dopamine theory of schizophrenia number one. The first dopamine theory of schizophrenia. There were several lines of evidence to support this. One line of evidence was that drugs that were more effective at blocking dopamine receptors in the brain, had greater clinical efficacy. There were a series of very important studies that were run by Phil Seeman at the University of Toronto. And in these studies, what Dr. Seeman found, was that when he looked at the degree to which different types of anti-psychotic medication actually block the action of dopamine, the more effective that these drugs were at blocking the action of dopamine, the less drug that was needed to treat patients clinically. So drugs that were very powerful at blocking dopamine receptors, required very little amounts of anti-psychotic medication to decrease symptoms. And similarly, drugs that were less effective at blocking dopamine receptors, clinically, doctors were required to use much larger doses of these drugs to attain the same effects as the more powerful anti-psychotic medications. Other data that supported this first dopamine theory of schizophrenia, was the use of amphetamines. People who recreationally used amphetamines to abuse, were found to develop a series of symptoms that in many cases were indistinguishable from schizophrenia. That is to say, people who took these amphetamines over long periods of time develop delusions, hallucinations, the types of positive symptoms that we've talked about earlier in the course. So both the fact that these anti-psychotic drugs interfere with the transmission of dopamine in the brain, and the fact that we take drugs that enhance the release of dopamine, such as amphetamine, produce a schizophrenia like syndrome. These findings together led to what are called the first dopamine hypothesis of schizophrenia. Which stated very simply, is that increases in level of dopamine in the brain lead to positive symptoms such as delusions and hallucinations.