"Using Fixed Circuits to Generate Flexible Behaviors"

Cori Bargmann, Ph.D.
Investigator, Howard Hughes Medical Institute
Torsten N. Wiesel Professor
Lulu and Anthony Wang Laboratory of Neural Circuits and Behavior
The Rockefeller University

RESEARCH
Environment, experience and genes 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. 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, the nervous system and behavior in the nematode C. elegans. C. elegans has a very simple nervous system that consists of just 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.

C. elegans’s most complex behaviors occur in response to smell, and these are at the heart of the Bargmann lab’s research. The tiny worm can sense hundreds of different odors, discriminate among them and generate reactions that are appropriate to the odor cue. Since its nervous system is so simple, it’s possible for researchers to determine how individual neurons contribute to these behaviors. 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 individual neuronal cells, calcium imaging from neurons in living animals and forward and reverse genetic approaches.

Bargmann is also investigating how much flexibility is present in a simple nervous system. 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 neurochemical changes that lead to rapid behavioral remodeling.

Another interest of the Bargmann laboratory is how genetic variation between individuals can cause them to behave differently from one another. In C. elegans, a single gene determines whether animals prefer to eat alone or in social groups. This gene encodes a neuropeptide receptor, a modulator that integrates multiple sensory inputs to generate coordinated behaviors. A current focus of Bargmann’s research is on learning how modulatory systems, like this neuropeptide receptor, affect the flow of information between neurons.

CAREER
Bargmann received her undergraduate degree in biochemistry from the University of Georgia. She received her Ph.D. in 1987 from the Massachusetts Institute of Technology (MIT), where she worked under Robert A. Weinberg at the Whitehead Institute for Biomedical Research. She pursued a postdoctoral fellowship with H. Robert Horvitz, also at MIT, until 1991, when she accepted a faculty position at the University of California, San Francisco. She remained there until 2004, when she joined Rockefeller as the Torsten N. Wiesel Professor. Dr. Bargmann also is codirector of the Shelby White and Leon Levy Center for Mind, Brain and Behavior. She has been an investigator at the Howard Hughes Medical Institute since 1995.

Bargmann is a member of the National Academy of Sciences, the American Philosophical Society and the American Academy of Arts and Sciences. She received the 2013 Breakthrough Award in Life Sciences, the 2012 Kavli Prize in Neuroscience, the 2012 Dart/NYU Biotechnology Achievement Award, the 2009 Richard Lounsbery Award from the U.S. and French National Academies of Sciences and the 2004 Dargut and Milena Kemali International Prize for Research in Basic and Clinical Neurosciences. Bargmann received the 2014 NIH Director’s Award for scientific vision and leadership and received the 2015 Benjamin Franklin Medal in the Life Sciences.

Bargmann is a faculty member in the David Rockefeller Graduate Program and the Tri-Institutional M.D.-Ph.D. Program.