The nervous system is a complex organ that functions in most metazoans to sense and respond to a constantly changing world. How the nervous system does this is a major focus of systems-level neuroscience. This dissertation investigates the neural basis of the sensorimotor transformation underlying a spatial orientation strategy in the nematode Caenorhabditis elegans. Motile organisms rely on spatial orientation strategies to navigate to environments that are conducive to organismal fitness and comfort, e.g. environments with the correct temperature, light level, or access to food and mates. As such, spatial orientation strategies as a class represent a key behavior common to most forms of life on earth. To explore the behavioral mechanism used by C. elegans for spatial orientation, we designed and manufactured a microfluidic device that breaks the feedback loop between self-motion and environmental change by partially restraining the animal. The device takes advantage of laminar flow at small scale to provide distinct environments across the dorsoventral undulation that constitutes locomotion in this animal without using a physical barrier. This device allowed us to conclude that worms use the change in chemical concentration sensed between lateral extremes of the locomotion cycle to direct forward locomotion toward a favorable stimulus, an orientation strategy termed klinotaxis. We then investigated the neuronal basis of this behavior using laser ablation, calcium imaging, and optogenetic stimulation. We found a minimal neuronal network for klinotaxis to sodium chloride including the ASE, AIY, AIZ, and SMB neuron classes that displays left/right asymmetry across the sensory neuron, interneuron, and motor neuron levels. We extended these results by ablating other neurons that have been implicated in klinotaxis in other studies. Finally, we imaged the ASE neurons during klinotaxis in microfluidic device and found that these neurons are active on the timescale of individual head swings. Additionally, we found anecdotal evidence that photostimulation of ASE neurons expressing the light sensitive ion channel Channel Rhodopsin (CHR2) is sufficient to stimulate klinotaxis behavior. This dissertation includes previously published co-authored material.