Steve Flavell joined the faculty of MIT in 2016. He received his B.A. From Oberlin College and his Ph.D. from Harvard University, where we worked with Dr. Michael Greenberg. Before arriving at MIT, Steve worked as a postdoctoral fellow in Dr. Cori Bargmann’s lab at Rockefeller University. Research in the Flavell Lab is aimed at deciphering the fundamental neural mechanisms that underlie the generation of long-lasting behavioral states. This work primarily focuses on the neuromodulatory systems that control arousal, motivation, and mood across organisms. Steve’s work has uncovered novel molecular mechanisms that allow signals from the gut to activate neuromodulatory systems, as well as circuit-level mechanisms by which neuromodulator release alters neural circuit dynamics. Steve’s work has been recognized by numerous national awards, including the Weintraub Graduate Student Award, Helen Hay Whitney Fellowship, NARSAD Young Investigator Award, NSF CAREER Award, Sloan Research Fellowship, and McKnight Scholars Award.
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.
9.12 Experimental Molecular Neurobiology
9.17 Systems Neuroscience Laboratory
Dag, U. Nwabudike, I., Kang, D., Gomes, M.A., Kim, J., Atanas, A.A., Bueno, E., Estrem C., Pugliese S., Wang, Z., Towlson, E., Flavell S.W. (2023) Dissecting the functional organization of the C. elegans serotonergic system at whole-brain scale. Cell, 186:101-119.
Flavell, S.W., Gogolla, N., Lovett-Barron M., Zelikowsky, M. (2022) The emergence and influence of internal states. Neuron, 110:2545-2570.
Ji, N., Madan, G.K., Fabre, G.I., Dayan, A., Baker, C.M., Kramer, T.S., Nwabudike, I., Flavell, S.W. (2021) A neural circuit for flexible control of persistent behavioral states. eLife, 10:e62889.
Cermak, N., Yu, S.K., Clark, R., Huang, Y.C., Baskoylu, S.N., Flavell, S.W. (2020) Whole-organism behavioral profiling reveals a role for dopamine in state-dependent motor program coupling in C. elegans. eLife, 9:e57093.
Rhoades, J.L., Nelson, J.C., Nwabudike, I., Yu, S.K., McLachlan, I.G., Madan, G.K., Abebe, E., Powers, J.R., Colon-Ramos, D.A., Flavell, S.W. (2019) ASICs mediate food responses in an enteric serotonergic neuron that controls foraging behaviors. Cell, 176:85-97.