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.