The Big Picture

Every thought, behavior and feeling we have is a result of how the cells in our brain are wired. How the nearly 100 billion neurons and 100 trillion connections between them form during development is an extraordinary mystery and one of the greatest challenges in biology. For a brain to be healthy and functional, these billions of neurons must connect in precisely the right way so they can communicate properly. Many neuropsychiatric disorders, such as autism and schizophrenia originate during brain development and may be caused by errors in the wiring process. How do neurons recognize the correct neurons to connect to? The answers to this question could transform the way we understand and treat mental illness and other neurological conditions.

The Science

Larry Zipursky's research is illuminating how neurons connect up correctly: he has discovered different labels that control how connections between neurons form during brain development. As a result of his groundbreaking research, the rules by which neurons navigate the complex environment of a growing brain are being defined. Knowing how this process of brain wiring works may allow scientists to gain insights into neuropsychiatric disorders. Zipursky’s research is changing our understanding of how the brain is built.

The Discoveries

  • Zipursky discovered the molecular basis of the first example of specific interaction between developing nerve cells in which one cell instructs another neighboring cell to become a specific type of neuron. Indeed, Zipursky's work has for many years been the textbook example of this type of communication during development. Local interactions between developing nerve cells known to be a central mechanism for building the brain.
  • A vast array of cellular labels allows neurons to discriminate between self and non-self. Zipursky discovered a large family of some 36,000 cellular labels. These labels are expressed on the many branches of axons and dendrites that neurons elaborate. The labels, in turn, allow the branches of a neuron to discriminate between its own branches and the branches of other neurons and to promote a critical process in brain wiring called self-avoidance. This work has provided fundamental insights into the strategies organisms have evolved to wire the brain.
  • Many cellular labels promote the formation of connections between neurons. Zipursky and his colleagues have identified many other cell surface proteins that allow the axons and dendrites of different neurons to interact. In a recent series of studies they demonstrated that neurons express hundreds of different labels. Among these labels, Zipursky described a set that are matched between the neurons that make synaptic connections with each other. Zipursky and his colleagues are doing experiments to understand how this system of labels promotes recognition between synaptic partners.

- By Emily Rose, Senior Strategy Officer, UCLA Health Sciences Development