How do a collection of neurons work together to receive information from the environment, encode that information, and then process it to generate purposeful behavior? The Leifer lab uses optical neurophysiology techniques, such as optogenetics and calcium imaging, to probe and peer into the neural activity of the small worm C. elegans and study the neural basis of behavior.

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Probing neural circuits

To probe the neural circuits underlying behavior, it is important to perturb and observe the activity of individual neurons and their effect on whole-organism behavior. The Leifer Lab specializes in developing non-invasive techniques to stimulate and record from ensembles of neurons across an organism with single-cell resolution in awake, intact, unrestrained animals whose behavior can be observed simultaneously. We build upon recent advances in the emerging field of optogenetics to use light to stimulate or inhibit neurons in a worm as it moves. We also use genetically encoded calcium indicators to record neural activity from all the neurons in the brain of the worm as it moves. And we use computer vision software to quantify and study the worm's behavior.

By systematically studying the collective neural dynamics that drive behavior, we hope to uncover general principles about the functions of neural circuits. To learn more please see videos of recent lectures, or recent articles about our work in the popular press.

Why C. Elegans?

Invertebrate model organisms can reveal fundamental principles of neuroscience. Insights into the molecular basis of learning and memory, for example, came initially from studies of Aplysia, a giant sea slug. Similarly, our understanding of motor circuits came first from early studies of leech and lamprey.

The nematode Caenorhabditis elegans is a powerful tool for studying the neuronal basis of behavior. With only 302 neurons, its nervous system is compact but tractable and the 1 mm-long nematode exhibits a rich array of behaviors. It senses its environment, navigates toward food and temperatures that it prefers, avoids chemicals that it dislikes, and responds to touch. The worm can even learn to associate neutral odors with food and then will seek out that odor accordingly, for example.

C. elegans is especially well suited to optical neurophysiology studies. The entire wiring diagram of the C. elegans nervous system (its connectome) has been mapped completely. The worm is easy to manipulate genetically, and its optically transparent body provides easy access for optical tools.

Video

For a recent introduction to the lab's research, see the video "How does a nervous system transition between behavior states?," from February 2016 by Andrew Leifer.