Genetic Identification of Attack Neurons in the Mouse

Aggression is a naturally occurring, instinctive social behavior, but pathological expressions of violence take an enormous toll on human society. 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 of 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.

Affiliated Investigators

David Anderson, Ph.D.

California Institute of Technology

David Anderson is professor of biology and Howard Hughes Medical Institute Investigator at the California Institute of Technology (Caltech) in Pasadena, CA, where he has been a member of the faculty since 1986. His research focuses on the mechanisms whereby stem cells generate the diverse specialized cell types of the developing nervous system. In 1992, his laboratory achieved the first isolation of a multipotent, self-renewing stem cell for neurons and glia from a vertebrate embryo. Subsequently, Anderson’s group identified extracellular signals that instruct the differentiation of such stem cells along various lineages, and transcription factors that act as master regulators of the neuronal and glial fates inside these cells. Anderson has also made contributions to the study of blood vessel development, including the first discovery of gene expression differences between arteries and veins, and the finding that nerve fibers determine the pattern of arterial branching in the developing skin. Dr. Anderson graduated from Harvard and received his Ph.D. degree at Rockefeller University, where he trained with Nobelist Günter Blobel. Dr. Anderson also performed postdoctoral studies at Columbia with Nobelist Richard Axel. He was elected to the National Academy of Sciences in 2007.