Research Goal and Significance
One central goal of neuroscience is to elucidate how learning is encoded and executed by the nervous system. To fully understand complex learned behaviors, we need to uncover the underlying neural circuits, define the properties of each functional node to address how a given circuit processes sensory inputs into motor outputs, illuminate the consequence of learning at each tier of the circuit, and characterize how these changes lead to learned behavior. We also need to understand how neuromodulators, such as amines and growth factors, set the global state of the neural circuits to modulate behavior. Our long-term goal is to achieve an integrative understanding of learning by addressing all levels of the underlying neural circuit from sensory perception to motor execution. Eventually, we will be able to test our understanding by manipulating learned behavior with genetic or optical tools, “writing in” experience-dependent changes to predictably modulate behavior.
System and Approach
To tackle these questions, we study learning in C. elegans. A major advantage of this system is that the complete anatomical connectome that describes the connectivity of all 302 neurons in its nervous system. Moreover, this well-defined nervous system can be dissected with powerful molecular, cellular and genetic tools. The functional properties of each neuron in sensorimotor transformation and learning – properties that are largely stereotyped among individuals – can also be characterized with optical neurophysiology in live animals as they perform complex, experience-dependent behaviors.
We focus on olfactory learning. Because olfaction plays an essential role in locating food sources, olfactory learning is similarly displayed across animal species. Thus, the underlying mechanisms are likely to be conserved. Olfaction is critical for C. elegans to navigate the environment, and the well-characterized olfactory neurons use conserved signaling pathways to process sensory inputs. We integrate quantitative behavioral analysis, molecular cellular genetics, optical imaging and ontogenetics in live animals that perform defined behavioral tasks to pursue a full scale model of learning that will ultimately incorporate all of the regulatory and modulatory elements in a small nervous system.