An animal's behavior arises from the interplay between its environment, its experience, and intrinsic properties of its neural circuits. To understand how genetic networks encode the potential of the nervous system, we are studying nervous system development and behavior in the nematode C. elegans.

How do animals detect and respond to a sensory stimulus? C. elegans senses hundreds of different odors, discriminates between them, and generates different behaviors in response to different odors. We can define the specific neurons that generate these behaviors, since the C. elegans nervous system consists of just 302 neurons with reproducible functions and synaptic connections. In C. elegans, as in other animals, odors are detected by G protein-coupled odorant receptors. A given sensory neuron is primarily dedicated to a single behavioral task, such as attraction or repulsion. Activation of a sensory neuron is sufficient to generate a characteristic behavior - indeed, artificial activation of a neuron can generate a completely artificial behavior to novel stimuli. We are asking how sensory signaling pathways and downstream neurons encode the flexible behavioral responses to sensory cues.

C. elegans shows unexpected sophistication in its behavior when challenged with complex stimuli that are present in the soil environment, such as pathogenic bacteria, other animals, and changes in oxygen levels. We are identifying genes and circuits for these navigation behaviors, and asking how sensory inputs regulate those circuits.

Much of the function of the nervous system is specified by its structure - the precise synaptic connections between neurons in circuits. We are studying the development of neural circuits by characterizing pathways for axon guidance, synapse formation, and neuronal differentiation. We are using genetic methods to study highly conserved signaling pathways for dorsal-ventral and anterior-posterior axon guidance. We have identified cell interactions between neurons and non-neuronal cells that direct synapses to form at precise locations during development. Finally, we have learned that signaling between neurons at the synapse can feed back onto neuronal differentiation to generate sensory diversity in the olfactory system.