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Genes, the environment, and experience interact to shape an animal’s behavior. Caenorhabditis elegans, a worm with just 302 neurons, shows considerable sophistication in its behaviors, and its defined neuronal wiring and genetic accessibility make it an ideal subject in which to study these interactions. Using C. elegans as a model, Bargmann’s laboratory characterizes genes and neural pathways that allow the nervous system to generate flexible behaviors.

How do genes and the environment interact to generate a variety of behaviors? How are behavioral decisions modified by context and experience? The Bargmann lab is studying the relationships between genes, experience, and behavior in the nematode C. elegans, whose nervous system consists of only 302 neurons with reproducible functions, morphologies, and synaptic connections. Despite this simplicity, many of the genes and signaling mechanisms used in the nematode nervous system are similar to those of mammals. The ability to manipulate the activity of individual genes and neurons in C. elegans makes it possible to determine how neural circuits develop and function.

The animal’s most complex behaviors occur in response to smell, and these are at the heart of the lab’s research. C. elegans can sense hundreds of different odors, discriminate among them, and generate reactions that are appropriate to the odor cue. These behaviors can be traced from molecules, to neurons, to circuits, to behavioral decisions. In C. elegans, as in other animals, odors are detected by G protein coupled odorant receptors on specialized sensory neurons. The odors that activate one sensory neuron regulate a behavioral output such as attraction or avoidance. The lab studies the pathways from sensory input to behavioral output by quantitative analysis of behavior under well-defined conditions, genetic manipulation of animals or individual neuronal cells, and calcium imaging from neurons in living animals.

The lab also asks how a fixed nervous system generates flexible behaviors. For example, C. elegans is capable of learning the odors of different bacteria and avoiding those that previously made it ill. These learned olfactory behaviors are associated with neuromodulatory signals that lead to behavioral remodeling. Other neuromodulators shape spontaneous behaviors in reversible patterns over minutes or hours. This reversible rewiring occurs without apparent changes to the fixed anatomy of the nervous system, and uses conserved molecules like dopamine, serotonin, and oxytocin, which are implicated in human motivational and emotional states. The lab is currently studying how neuromodulatory systems affect the flow of information between neurons across different timescales.