The amygdala is the orchestrator of the emotion positive and , negative. It influences the hypothalamus. The hypothalamus has many functions but we will focus on its role in aggression and sexuality. We are basic neuroscientists in my lab, and we want to understand some of the most fundamental questions about aggression. How is aggression, a revolutionary ancient behavior, throughout the Animal Kingdom how is that hardwired into the , brain . Where is aggression in the brain . We have studied this problem in flies and mice and were particularly interested in the relationship between the parts of the brain that control aggression and those that control mating or sexual behavior. As you know mating and , aggression are closely related behaviors. In nature you often find that periods of aggression are at their highest when animals are mating. These behaviors reinforce each other. At the same time, they are mutually exclusive. A male will direct mating towards a female of the species , aggression towards another male. Theres a paradox. How can these behaviors be mutually exclusive but also reinforce each other in some way . We have begun by trying to pinpoint the neurons that control aggressive behavior and we have started by looking in a very evolutionarily ancient region of the brain, which eric brought up, called the hypothalamus. We began by trying to measure the electrical activity of cells that were active during aggression or mating, in a tiny region of the hypothalamus. We found something quite surprising. Within this very small region of the brain we found a mixture of neurons, some of which were active, turned on when the animals were fighting, this was done in males, some of which were turned on when the animals were mating with a female, and interestingly some of these were , active during both fighting and mating, 25 of them overlap. That was an interesting observation, a correlation, and we really wanted to understand the function of these neurons. We began by using very modern techniques now called opto genetics to activate and inhibit these neurons. We can pinpoint this activation with a high level of accuracy, directly to specific cells in the brain active during aggressive aggression, and turn them on and off with a time resolution of milliseconds. Im going to show you a video of what happens to a male mouse when you activate these aggression neurons in the brain. Before the video, some of your viewers might find the image of it disturbing, but we are not hurting the mouse. These are all protocols that have been approved by our institutional animal use and Care Committee and nih approved. You will see the mouse in a cage with an inanimate object. When the light comes on we are stimulating these aggression neurons in the mouse. We can actually trigger the mouse to attack a rubber glove. If there were another mouse there he would attack the other mouse as well. We wanted to ask, are these neurons necessary for normal aggression . Mice will normally fight for with each other, for example if you introduce an intruder mouse into the cage where a male mouse lives, very shortly thereafter the resident mouse will attack the intruder. He does not like somebody impinging on his territory. We ask if we shut these neurons off, can we stop a fight dead in its tracks . As the next video will show you, its possible to do that. These mice are fighting naturally. When the light comes on we inhibit these neurons and the fight stops. We will show you that again in slow motion. The mice are fighting and suddenly the light comes on, we stopped the attack dead in its tracks. Charlie i dont understand how neurons know how to respond to light. Do this iswe genetically implant in these neurons in the brain, a protein that comes from a lightsensitive algae. That protein makes an ion channel through the membrane of the neuron that turns the neurons on, only when light activates the channel. We can convert these neurons into lightsensitive neurons. That shows us the neurons are necessary and sufficient for aggression. There are different kinds of ones, those that activate the neurons and those that shut off. We can do either. We discovered, as we were manipulating, the conditions for turning these neurons on very surprising. You needed high intensity stimulation to activate aggression but low intensity stimulation would promote mounting behavior. The mouse would try to meet with whatever other mouse was in the cage with low intensity stimulation, whether it was a male mouse, female mouse, it would try to mount. We could actually switch the behavior of the same animal from attempted mounting to a mixture of mounting and attack just by increasing the intensity of light. That tells us that in this tiny region of the brain there is a mixture of neurons controlling both the mating instinct and the fighting instinct, and perhaps that will account or may account for the tension between the sex drive and the aggressive drive. Charlie its extraordinary. It is extraordinary. It also sort of explains why aggression can lead to sexual aggression. It really is an amazing set of findings. A lot of people think aggression is more prevalent in people with Mental Illness. The fact is Mental Illness on his own does not increase the rate of aggression. It is more likely to occur in individuals with issues of Substance Abuse and dependence, and especially prior history of aggression. Everyone gets very concerned when Mass Shootings happen. This person must be mentally unfit. Those are very individual situations. When you look across large epidemiological studies, that does not pan out. There are multiple forms of aggression. There is socially sanctioned aggression, such as fighting in war, medically induced aggression. A medical condition makes more makes one more irritable. But the two big ones will be impulsive aggression and premeditated aggression. Impulsive aggression is not exactly spontaneous. People get or perceive a threat or frustration and their , threshold to blowup is very low. They just blowup or display a temper touch or more physical temper tantrum or physical aggression. Premeditated aggression, which can happen in anybody, is taught already thought through. The people most likely to do that is psychopaths, maybe 1 of the population. But people have intermittent explosive disorder, which is more like 3 or 5 to 6 . That is much more the case as far as that is concerned. Those important distinctions to put forth, because we have an idea of how to treat impulsive aggression. We are not quite sure how to treat premeditated aggression. We will Say Something more about that. Charlie what did we see at the neurobiological level . People with aggression is similar to what were hearing at this table. The doctor talked about 4 of boys being chronically aggressive. That is about how many ieds you have out there. We also see the same sort of thing biologically pretty see problems with serotonin function, where serotonin function is diminished. We see evidence of heightened other neurotransmitters that will facilitate aggression. We see problems in the frontal area of the brain. When we present to these individuals, pictures of individuals who are angry or threatening, the amygdala will overact to that stimulus compared to healthy volunteers. That also correlates with how aggressive these people have been over the course of their lives. An important thing going along with this is serotonin and the amygdala really have to do with the tendency to be aggressive. What makes you aggressive in the here and now has to do with how you interpret social signals. People that are aggressive it may very well be because they had been aggressive as a child tend to have problems of social internation processing. They dont take in enough information about whats going on and they make a hostile inference as to what the other people is doing. You can have a situation where the threshold may be high or low , and where you are coming into to day is you are primed think somebody brushed up against you or is looking at you funny, is threatening or frustrating to you. You have a serotonin system in the frontal lobe that is not working so well. Brakes are bad, high accelerator, you will have a crash. Charlie and i did a program on depression. One of the key things is treatment of depression often is designed to increase the level of serotonin. Is there a increased incidence of this kind of aggression and people who are depressed and have low levels of serotonin . Not necessarily. The early studies i did were interesting in that. We saw this problem in individuals who did not have a primary mood disorder. And what we think is going on is their brain systems involved in activation are not working well. They will make a Suicide Attempt when they are severely depressed because that is the arousal going on. When you have low serotonin, it is bad breaks. Charlie we talked about certain individuals who cannot control their impulses. Yes m. L. Has been talking , about people in a hospital context. What we do is we work with people at the street level were violent psychopaths, even killers. Charlie what the psychopath mean . An individual who lacks conscience, remorse, guilt. Because of that lack of normal emotional feelings, there are no areas. They do outrageous things. There are no barriers. They do outrageous things. There stimulation seekers, their impulsive. There are two types. There is the cold, calculating, callused type. Then you have the antisocial lifestyle, doing horrible things to other people. We have been studying their brains using brain imaging to look to see what part of the brain may not be working right, what part may be physically different. What we find in normal people is that their prefrontal cortex is working well, as you see there, in the green. This is where we brain scanned murderers in the next slide. What we see our murderers who are impulsive, they do not plan the murders they are hotblooded , in terms of their homicide. And what we see on the left is poorer functioning in that frontal region of the brain. Why is it that that part of the brain can predispose to aggression . It is a part of the brain involved in checking on impulsive behavior. We all get angry at times. What stops us lashing out . We have a good frontal cortex that is working well to regulate and control our aggressive behavior. Those are hotblooded murderers, but what about the coldblooded murderers . When we brain scan them, they had pretty good frontal functioning, which makes sense because these are killers who premeditate their homicide. They are planning ahead. They had the wherewithal to do that. The interesting question becomes, what is it then that is producing them to be violent in a predatory fashion . Lets turn to the next slide. We will look at another brain region. This is the amygdala on the left. You can see where it is located in the brain. When we study coldblooded offenders, psychopaths, they have a physical shrinkage in the amygdala. It is reduced in size by 18 . On the right, you can see the areas within the amygdala colored in blue that are actually physically deformed. The amygdala is important in generating emotions. If there is a shrinkage, that will reduce fear. What stops a lot of us breaking the law of the lands, we are frightened about the punishments we would get if we were caught. But if you lack that fear, you are more likely to commit offenses in a coldblooded fashion. Theres more to it than that. On the left you can see where it is located in the brain. Another brain region. On the right, you can see theres greater activity in psychopaths when they are anticipating rewards. We have the idea that psychopaths are reward driven. They want the goods, just like an addiction. Charlie there is stimulation to the brain . The idea is the anticipation reward is part of the brain, firing up a lot more. Maybe that is why psychopaths are more likely to pursue rewards and gains that they want. They have the drive to do that. And they dont have the emotional amygdala to hold them back in a way to give them anticipatory fear. That would normally result. This is a spectacular series of findings. When i was a medical student, none of these imaging techniques were available. You had very little insight of what was going on and the living brain of people. We now have insight into the biological substratum of different kinds of aggressive syndromes. This is just the beginning, how much we have learned, different categories, impulsive versus premeditated, different categories. Charlie even affecting the size of the amygdala. The question is, because of your reference to imaging, can you look at imaging and decide it is most likely to be aggressively violent . Its a great question. We are beginning to get clues about who may be more likely to be violent in the future. Myself and colleagues brain scanned males in the community. Those individuals with a smaller volume to the amygdala were more coldblooded. So to speak. They were four times more likely to commit a violent act in the next three years. That is prediction over and above prior history of violence, prior history of psychopathy. It not perfect by any manner, but we are beginning to get value used by imaging to try to understand who are at risk for becoming the next generation of future offenders. Charlie are we seeing this kind of research used in trials, in criminal trials . The key question here is if a psychopath is what is causing that amygdala shrinkage . It could be genetic. It could be how the brain develops. We also know that trauma reduces the size of the amygdala in children. Neglect reduces the size of the amygdala. For whatever reason, i dont think psychopaths ask to be born with an amygdala three sizes too small. If that brain empowerment impairment predisposes them, alters them, doing the terrible things they do, the fascinating question is to what extent do we , hold them fully responsible for their actions . This is not dna evidence. This is not like saying, i am responsible, david is not definitively. This is a probabilistic statement, and that is imperfect in front of the law. Absolutely. I think as techniques get better, and not only the amygdala the amygdala is , associated with abnormality, danger is associated with another abnormality, we will be in a better position. Human parents, this behavior is essential for the Proper Development of the child heard. In addition, parenting is one of the strongest and most enduring social bonds in human societies. Remarkably, parental behavior is wildly conservative in the Animal Kingdom. In mammals, females lactate and therefore they take primary responsibility of parental care. As you can see in this slide, female chimpanzee is watching over the first child. Females are very flagrantly maternal, not only in mammals but also some species of birds, reptiles and insects. What about the fathers . The contribution of males in parenting is very variable. In some species, for example in the silverback monkey and gorilla playing with his infants, in some species males are paternal, they nurture their young. In some other species, males attack the children and sometimes kill them. I am a neurobiologist. My group used a Laboratory Mouse to try to understand basic biology of parenting behavior. We would like to identify the brain areas that are involved in driving parental behavior and we would like to understand how these brain areas are regulated, in order to have animals that are parenting and some animals that are neglecting their infants. In females, mothers as well as nonmothers are spontaneously maternal. Which means that when they are put in the presence of pups they , will spontaneously build a nest, they will retrieve them they will groom them, and huddle , with them for long periods. In contrast, males are infanticidile. They will readily attack pups and kill them. However, males that have access to the females become paternal three weeks after meeting with a mating with a female which corresponds exactly to the , gestation time in mice. In other words, males who become fathers also become paternal. We took advantage of these extremely interesting paradigm and differences in behavior between males and females and infanticidal males to try to understand what are the brain role. What are the neurons that drive parental behavior . In the first set of experiment we identified a specific set of cells in the hypothalamus that are activated during parental behavior. We then ask all these neurons, required for the parental drive. In a subsequent experiments, we ablated these neurons in parental males and females. Surprisingly and remarkably, now these animals neglect their infants or attack them. These experiments suggest these near runs are required for a neurons are required for parental behavior. In the next experiments, we ask whether the activity of these neurons was sufficient to create parental behavior. Took aggressive males and artificially stimulated these nurturing neurons. Amazingly, these aggressive males stopped attacking the cubs and they groomed their infants. What this experiment says is the activity of these neurons is sufficient to drive parental care. In another experiment, we identified a set of cells in a different area of the hypothalamus that is activated when aggressive males attack their infants. We call these the parental neglect neurons. In another experiment, we activate these neurons in females and found these females, instead of caring for their infants, now neglect or attack them. So what over all these experiments suggest is that the brain has two components. A set of cells in the hypothalamus that drive parental behavior, and another set of cells that drive parental neglect. These very excited by results, because it opens new opportunity to understand the behavior, parental and possibly why some animals are parental and some are neglecting or attacking these infants. Parental behavior is widely conserved among animals. Also raises the possibility that the function and regulation of the cells is widely conserved across the Animal Kingdom. Charlie one question before we go to suzanne. How do you stimulate the neurons to make the aggressive males more nurturing . Catherine we use modern methods in neuroscience called opto genetics, that are able to shine light on neurons that have been genetically modified and have an ion channel that is light activated. In other words we drive the , activity of genetically defined population of neurons. There is been fascinating work done by teams understanding the evolution of parenting behavior and of bonding between males and females. In both there is a very nice , system where some species are polygamists and some are monogamous. Excellente vole is an example of the monogamous system, where males and females form these long time pair bonds and both are nurturing towards their young. What has been found in this system is that not only are the higher levels of oxytocin, but in the males there is a similar hormone produced by the hypothalamus which seems to be important in determining both paternal behavior and pair bonding b