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Watching the Thoughts of Worms
Summary: Rex Kerr builds and uses advanced volume-imaging microscopes to study how behavior in C. elegans is generated by activity in its nervous system.
Understanding how the collective activity of neurons gives rise to behavior is one of the great challenges for biology in this century. This task is especially daunting because it is difficult to both monitor the activity of the relevant neurons in behaving animals and quantify behavior precisely. We are addressing this problem by developing microscopy tools and experimental techniques with which to study the model organism with the simplest and best-characterized nervous system, Caenorhabditis elegans. We hope that this will allow us to develop key insights into the control of behavior by neural circuits and reveal the genes that are required for the function of these circuits. It is our expectation that these lessons can then be applied to larger organisms, where the technical challenges are greater.
We will focus on three areas that are essential for a detailed quantitative understanding of the relationship between neuronal activity and behavior in C. elegans.
Advanced Volumetric Microscopy
Adult C. elegans have only 302 neurons, half of which are located in the animal's head. To relate behavior to neural activity, we must monitor the activity of these neurons. We are developing hardware and software that allows us to rapidly construct three-dimensional movies of the worm's head. By using fluorescent probes that indicate neuronal activity, we can simultaneously monitor and quantify the activity of a large number of neurons. Due to the small size of the organism and short exposure times, the primary technical challenge lies in capturing enough photons from the sample to obtain an accurate report of neuronal activity. Imaging and image-processing techniques developed by or in collaboration with Eric Betzig and Eugene Myers (both HHMI, Janelia Farm Research Campus) may prove essential for overcoming these challenges.
Population-wide Behavioral Quantification
The behavior of individual worms can be quantified by computer tracking systems that follow individual animals as they move and behave. Behavior is often variable, however, so it is necessary to collect statistics from a population of dozens of individuals to gain an accurate picture of behavior. We are developing tracking systems that simultaneously monitor an entire population of worms. This allows the behavior of a single strain of worms to be quantified dozens of times faster than with single-worm tracking. This speedup is especially important because it can reduce the time needed to screen thousands of lines of potentially mutant worms for abnormal behavior. In this way, population behavioral quantification can uncover genes that are essential for complex behaviors. Initially, in collaboration with Catharine Rankin (University of British Columbia), we will focus on identifying genes specifically involved in habituating to repeated taps.
Genetic and Neuronal Basis of Behavior
Once the volumetric microscopy techniques are established, we will use them to study the neuronal basis of simple and complex behaviors in C. elegans. For example, the pattern of activity in the motor nerves that gives rise to the sinusoidal pattern of motion is not known, nor is the pattern of chemosensory neuron activity in response to behaviorally salient chemicals; these will be directly observable. The consequences of these activity patterns depend upon the connectivity between the individual neurons. Therefore, we will work with Dmitri Chklovskii (HHMI, Janelia Farm Research Campus) to develop and test hypotheses regarding the function of the observed patterns of activity. We also will study the circuitry involved in specific behaviors from sensation through motor output. For example, worms respond to being touched by moving away from the touch. This behavior involves sensation, information processing by interneurons, and finally muscle contraction caused by motor neurons, and the behavior can be modified by learning. We will describe behavior and learning in terms of patterns of neural activity. This approach is complementary to standard methods used by the C. elegans research community. We therefore anticipate close collaborations with other C. elegans labs to use the imaging resources of Janelia Farm to gain key insights into the genetic and neuronal basis of behavior.
Last updated: October 23, 2007
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