CAREER: Mechanistic dissection of sleep and behavioral arousal: A model system approach to interdisciplinarity in neuroscience research and education

California State University, East Bay Foundation, Inc., Hayward CA

Investigators

Abstract

Sleep and wakefulness are highly conserved and fundamental behavioral states. The ability to regulate these states in response to environmental conditions and homeostatic needs is critical for survival. Goal-directed motivated behaviors like mating, feeding and aggression are essentially dependent on strong behavioral arousal. Nonetheless, little is known about the neuronal mechanisms that compartmentalize and coordinate motivational processes with sleep-wake regulation. Here, the investigators determine how arousal states are encoded and integrated across behaviors in the brain by studying the behavioral coordination of sleep and social behaviors like courtship using the experimental tractability of the fruit fly Drosophila. The focus on small circuits with measurable behavioral outputs in organisms amenable to genetic manipulations and neurophysiological recordings generates resources and expertise that exposes middle-school, high-school, undergraduate and graduate students to interdisciplinary research. The research and educational programs in this project act synergistically to support college students to integrate skills and concepts across disciplines through research engagement, career mentoring, skills-training, interdisciplinary thinking, and teaching practices. Circuit mechanisms underlying the coordination of sleep and behavioral arousal are not understood in any organism. The focus of this project is to define the circuit mechanisms by which sleep and wake are encoded in the fly brain and how they causally influence arousal states associated with motivated social behaviors like courtship and aggression. The research team has identified integrator neurons that encode motivation to court and also mediate wakefulness and arousal. This project investigates the mechanisms by which these integrator neurons initiate and maintain arousal to co-regulate sleep expression with motivated behaviors. The investigators have established Drosophila as an advantageous model for circuit analysis of co-regulation of sleep and behavioral arousal by developing novel behavioral assays, tools to target individual cell-types and record network activity where this co-regulation has been destabilized. In Aims 1 and 2, studies map excitatory and inhibitory synaptic interactions between integrator P1 network and sleep-regulating neurons of clock network, Mushroom Body and Central Complex that underlies the bidirectional control of sleep and social behaviors. In Aim 3, measurements are made of the spontaneous neural activity of identified microcircuits animals with destabilized sleep- or social-arousal states. This project will establish connections between genes, circuits, and behavior in understanding internal state dependent decision making and action-selection. 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.