Neural Regulatory Mechanisms that Link Metabolism and Behavior in Caenorhabditis elegans
The neurotransmitter 5-hydroxytryptamine or serotonin, functions as an indicator of food availability and is an ancient mechanism by which invertebrate and vertebrate species translate sensory information about food availability and quality to distinct nutrient-related behaviors and physiologies. Serotonin signaling is influenced by internal and environmental signals and coordinates a wide range of behaviors related to nutrient status including appetite, reproduction, growth, learning, memory and mood. Despite these fundamental roles, the precise mechanisms that link neural serotonin to physiologies occurring in distant peripheral tissues remain poorly understood. Moreover, little is known about the mechanisms that link internal metabolic signals from peripheral tissues to neural serotonin circuits to regulate behavior. In this work, we leverage the experimental advantages of C. elegans to investigate these two distinct yet coordinated aspects of serotonin signaling. In chapter I, we examine how neuronal serotonin signaling communicates to distant tissues to regulate behaviors like movement, development and fat metabolism. In chapter II,III and IV, we identify the metabolic, molecular, and cellular components of a novel gut-to-brain regulatory axis that links peripheral metabolic signals to serotoninergic circuits that regulate behavior. Together, this work highlights the influence that peripheral metabolic signals exert on neuroendocrine signaling cascades and offers mechanistic insights into how nutrient cues modulate a neuromodulatory mechanism implicated in the control of mood, cognition and behavior.