Neural Mechanisms that Underlie Flexible Sensory Control of Behavioral States in C. elegans

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The behavioral state of an animal – whether it is active, inactive, mating, or fighting – profoundly influences how it generates behavioral responses to environmental cues. However, because the environment is constantly changing, animals often switch behavioral states in a sensory-driven manner. Over longer timescales, experience and physiological changes may further bias animals towards certain states. For example, a starved animal may exhibit a higher probability of switching to a stable dwell ing state upon smelling a food odor, compared to a fed animal. How the nervous system flexibly changes so that animals generate context-appropriate behavioral states remains poorly understood. To understand how sensory cues influence behavioral states and how the links between sensory cues and behavioral states can flexibly change, it will be critical to examine how neurons at the sensory periphery feed into key neural populations that control behavioral states. Physiological changes like starvation may influence sensory circuits themselves, as well as the interactions of these circuits with downstream neurons that control behavioral states. The C. elegans nervous system is particularly attractive for these types of whole-circuit problems in neuroscience because (a) it consists of exactly 302 neurons, (b) every neuron can be identified in every animal, (c) the synaptic connections between these neurons are known, and (d) genetic tools allow us to manipulate single cells in this system. While feeding, C. elegans switch between two stable behavioral states: dwelling states, where they reduce their movement to exploit a food patch, and roaming states, where they display fast locomotion to explore for a better food source. The generation of roaming and dwelling states is influenced by the animal’s ingestion of food, detection of olfactory cues, and satiety. Although it is clear that these states are influenced by olfactory cues and satiety, the molecular pathways and neural circuits that mediate these effects are poorly understood. Here, we propose to build off new preliminary data that gives us a unique opportunity to uncover these mechanisms. We found that food deprivation leads to a broad change in olfactory receptor expression in food-sensing olfactory neurons, which in turn impacts the roaming/dwelling state of the animal. We have also characterized the functional architecture of the core neural circuit that generates roaming and dwelling states. This now gives us an opportunity to examine how inputs from a defined set of chemosensory neurons (whose sensory receptors dynamically change) are integrated by downstream circuits to flexibly control behavioral states. We will first uncover molecular and neural pathways that allow diverse external and internal cues to modulate olfactory receptor expression in defined C. elegans neurons (Aim 1). Then, we will examine how ensembles of chemosensory neurons influence activity in the roaming-dwelling circuit across satiety states (Aim 2). This work will result in a new paradigm for understanding how populations of neurons at the sensory periphery flexibly control behavior.