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Finding the Neural Basis for Aggressive Behavior

11/18/2010

Finding the Neural Basis for Aggressive Behavior

11/18/2010

Investigator: Dr. David J. Anderson, Ph.D.
Institution: California Institute of Technology
Project Title: “Finding the Neural Basis for Aggressive Behavior”
Award Amount: $1.6 million (2010)

Aggression is a naturally occurring, instinctive social behavior, but pathological expressions of violence take an enormous toll on human society. Domestic abuse, rape, gang violence, bullying, school shootings, and assault are all pathological expressions of aggression. Yet we know relatively little about the genetic and environmental mechanisms that predispose certain individuals to sociopathic violence, and we lack specific drugs for the treatment of aggressive disorders. What's needed is an understanding the basic neural circuitry of aggression.

In the 1920s Nobel laureate Walter Hess showed that attack behavior can be artificially elicited in an otherwise docile cat by electrically stimulating a region of the brain called the hypothalamus. The Allen Distinguished Investigator research effort supported here addresses several questions previously left unanswered: Which neurons produce attack behavior when stimulated, and where are they located? Are these neurons required for naturally occurring territorial aggressive behavior, or are they only recruited by artificial brain stimulation? What role do these neurons play in controlling aggression, and are they used only for this purpose or are they employed in other types of instinctive behaviors as well?

Revolutionary advances in technologies for marking, mapping, and manipulating genetically defined subsets of neurons have made it possible, in theory, to answer these questions decisively in the laboratory mouse. The current research first identified several genes that mark candidate neurons in the region of the hypothalamus implicated in aggression and then created lines of transgenic mice in which these neurons can be genetically manipulated to determine their role in aggression. The research shows that activating these neurons causes mice to attack inappropriate targets, such as females or inanimate objects, while inhibiting these neurons can almost instantaneously stop a fight between two male mice. Interestingly, a subset of these neurons appears to play a role in male mating behavior as well, indicating that the neurons involved in sex and violence are intimately associated in the brain. This breakthrough discovery now opens the way to systematically tracing the neural networks in which these neurons are embedded and understanding how these networks encode aggressive and other social behaviors.