Steven Flavell

Action potentials and synaptic transmission occur over the time scale of milliseconds, yet the brain generates behaviors that can last seconds, minutes, or hours. A major goal of neuroscience is to understand how neural circuits generate coherent behavioral outputs across such a wide range of time scales. Long-lasting behavioral states—including arousal states (sleep, wake) and complex internal states (emotions)—are thought to be controlled by biogenic amine and neuropeptide neuromodulators. However, we still have a poor understanding of the basic neural mechanisms that underlie behavioral state initiation, maintenance and termination. Moreover, it is unclear how external and internal cues, like satiety status, alter the outputs of the neural circuits that control these states. The goal of our laboratory is to understand how neural circuits generate sustained behavioral states, and how physiological and environmental information is integrated into these circuits.

The problem of studying the interactions between neuromodulators, neural circuits, and behavioral states can be simplified in the nematode C. elegans. In addition to classical neurotransmitters, the C. elegans nervous system utilizes neuropeptides as well as biogenic amines like serotonin and dopamine. The nervous system of C. elegans is a simple, well-defined model system: it contains exactly 302 neurons, every neuron can be reproducibly identified in every animal, and a complete connectome has defined all of the synaptic contacts between these neurons. In addition, we can use a variety of precise genetic tools to manipulate each neuron in this nervous system.

By combining quantitative behavioral analyses with genetics, in vivo calcium imaging, and optogenetics, we have mapped out neural circuits that generate behavioral states and characterized the activity of neurons within these circuits during different behavioral states. Our current research aims to expand our knowledge of how neuromodulators like serotonin organize the circuit-wide patterns of neuronal activity that emerge from these circuits as animals switch between behavioral states. We are also investigating how these neuromodulatory circuits integrate environmental and physiological cues that influence behavioral state generation, such as satiety status.