Brain-wide representations of olfactory behavior in C. elegans

Abstract

Olfactory navigation emerges from dynamic interactions among sensory input, brain activity, and the animal's own movements. The small size and optical transparency of C. elegans allow for multi-neuronal imaging of its nervous system in response to defined olfactory environments, from the sensory periphery to brain-wide scales. Its undulatory locomotion allows navigational behavior to be reduced to stimulus-dependent transitions between forward, reverse, and turning motor states. In this dissertation, we studied the sensorimotor transformation underlying olfactory behavior at complementary levels of the circuit. We used brain-wide tracking microscopy to record neural activity in freely crawling worms navigating spatial odor gradients or isotropic environments, and in immobilized worms responding to temporal odor pulses. Across conditions, we identified strongly correlated brain-wide activity patterns spanning olfactory sensory neurons, interneurons, and premotor neurons. Motor-state transitions and brain-wide correlation structure differed between freely moving and immobilized animals, demonstrating that olfactory sensory representations depended jointly on sensory input, motor activity, and behavioral context. Together, these findings showed that brain-wide representations of olfactory behavior are extensively reconfigured by sensory input, self-motion, and behavioral context. Zooming in on the sensory periphery, we used multi-neuronal imaging of the amphid chemosensory neurons to extend prior characterization of odor identity coding from single-molecule odorants to naturally derived pheromone mixtures. We applied the same imaging platform to study the molecular mechanisms of sensation of the anticonvulsant valproic acid. Together, these studies span multiple levels of the C. elegans olfactory circuit, from how chemical stimuli are encoded by the sensory periphery to how this information is integrated across the brain to drive navigation. They illustrate how the combination of multi-neuronal imaging and a compact, fully mapped nervous system can be used to dissect sensorimotor transformations from input to output, and underscore the importance of studying neural activity in unrestrained, behaving animals.