Many animal behaviors are organized into long-lasting states, perhaps most strikingly in the three main arousal states in mammals: wakefulness, non-REM (rapid eye movement) sleep, and REM sleep. Although behavioral states are pervasive throughout the animal kingdom, the fundamental mechanisms that allow animals to initiate, maintain and terminate these states are poorly understood. To address this problem, the researchers examine the brain mechanisms that underlie behavioral state generation in a simple animal model, the roundworm C. elegans. Specifically, they examine how groups of interacting neurons --or neural circuits-- contribute to the generation of behavioral states. C. elegans is an attractive system for these studies because its nervous system consists of just 302 neurons. Moreover, the connections between these neurons are already known. Thus, fundamental principles of neural circuit function can be rapidly discovered in this animal and then applied to more complex animals. The specific goals of the research plan are to (1) fully characterize behavioral states in C. elegans, (2) examine how groups of neurons interact during behavioral states, and (3) use new optical approaches to characterize brain-wide activity during behavioral states. These studies will yield new insights into how animals generate behavioral states, with implications for human well-being, public policy, and more. This research plan is integrated with an educational plan centered on developing an undergraduate laboratory course where students learn and apply modern neuroscience methods to study neural circuits. The course materials will be made freely available to other educators.
A full understanding of neural circuit function requires detailed knowledge across many scales of analysis: from molecular events in single neurons to large-scale patterns of neural activity to emergent animal behaviors. This research project bridges these scales of analysis in the context of neuromodulatory control of long-lasting behavioral states. Although almost all animals display long-lasting behavioral states, the neural mechanisms that allow animals to generate these states are poorly understood. The goal of this project is to dissect these mechanisms in the simple nervous system of the nematode C. elegans, linking specific sites of neuromodulator release to large-scale activity patterns and behavior. Aim 1: First, a novel imaging platform will be used to determine how all C. elegans behaviors co-vary over time as animals switch between behavioral states. Aim 2: Targeted mechanistic experiments will then be used to examine how specific neuromodulators allow for state-dependent coupling between premotor circuits to coordinate behaviors as animals switch states. Aim 3: Finally, a whole-brain calcium imaging approach will be used to examine brain-wide activity patterns during behavioral states. These studies will reveal fundamental neural mechanisms that allow animals to coordinate and structure their behaviors. This research plan is complemented by an educational plan, which is centered on the development of a new undergraduate laboratory course in which students learn and apply modern neuroscience techniques to dissect neural circuit function. The course has an emphasis on the use of diverse experimental approaches to probe neural circuit function.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
