State-dependent modulation of neuronal circuits underlying sensorimotor decisions – NeuroMOD

Hunger is a strong motivational state able to alter a broad range of behaviors. Howvere, how hunger is integrated in circuits underlying nonfeeding decisions is unknown. This is primarily due to the difficulty in establishing causal relationships between single neurons and behaviors and the challenges in determining the connectivity between these neurons at a synaptic resolution. In addition, it has been challenging to determine how neuromodulators can reconfigure the activity in neuronal circuits across the nervous system. This project will discover the basic principles by which nonfeeding-related neural circuits are modulated by hunger in a tractable model system: the Drosophila larva. First, using automated and quantitative methods, we will discover the behavioral rules of context and state-dependent changes in escape decisions. Second, by building on our preliminary work of synaptic-resolution mapping of the neural circuitry underlying sensorimotor decisions, we will identify, using structural and functional approaches, the connectivity patterns underlying state-dependent flexible escape decisions. We will determine the role of descending pathways in state-dependent modulation. Finally, using intracellular recordings, computational modeling and genetic manipulations of signaling pathways, we will discover the mechanisms by which neuromodulators reconfigure neural circuits to integrate hunger in neural computations. Altogether this interdisciplinary approach will allow us to address the challenging question of the way in which neural networks can produce different behaviors depending on internal physiological signals.
Understanding the basic principles of how internal physiological states, like hunger regulate behavior at different scales from molecules and circuits to neural networks and behavior will open avenues for novel therapeutics for eating disorders as well as strategies for modulating maladaptive behaviors in general.