Dense Mapping of Dynamics onto Structure in the C. elegans Brain

In the human brain, billions of neurons wired into networks sense the environment; process, store, and retrieve information; and produce thoughts and behavior. However, it’s not understood how the activity of neurons gives rise to these cognitive processes. A major program of neuroscience is to address this question by building so-called “connectomes,” or complete wiring diagrams of the connections among neurons. These efforts are occurring in a variety of organisms, including humans. However, the projects are challenged by the sheer complexity of the connectomes, even in simple organisms such as fruit flies and mice. There is also a lack of a functional framework to interpret anatomical data from connectomes. The lack of a functional framework is most readily apparent when considering the story of the simple worm known as C. elegans. 25 years ago, the connectome of C. elegans was mapped in exquisite detail— and C. elegans remains the only organism with a complete wiring diagram—yet it is still largely unknown how this brain produces any type of behavior. Taking advantage of the relative simplicity of C. elegans, our lab has developed a new microscopy technology that can, for the first time, capture the real-time activity of every neuron in a whole brain. We will use this platform, coupled with a new experimental approach to arouse the worms into action with complex stimuli, as well as sophisticated computational methods, to unravel the relationship between the connectome and functional activity in the worm brain. This basic “function-from-structure” question is of fundamental significance to the multitude of brain-mapping projects underway in more complex organisms. Our work in the worm will establish a baseline for how useful a connectome is to elucidating brain function, influencing a range of connectome projects, including those involving the human brain.

Manuel Zimmer, IMP Research Institute of Molecular Pathology GmbH