All forms of life, ranging from bacteria to humans, are intimately affected by ambient temperature which constantly fluctuates. To survive and thrive, animals and humans have evolved sensory systems, which comprise thermosensory neurons/circuits and molecular thermal sensors to detect, respond, and adapt to temperature changes in the environment. Defects in temperature perception lead to neurological and metabolic disorders. Research in the past two decades has led to an increasingly clear understanding of how animals sense heat, including the identification of various types of heat-sensitive neurons/circuits and channels/receptors in diverse organisms ranging from worms to mammals, which reveals a remarkable conservation in the mechanisms of thermosensation. By contrast, much less is known about how animals sense cold temperatures. Here, using state-of-the-art thermoelectric technologies, we have developed novel thermoelectric devices to rapidly and precisely change ambient temperature. By taking advantage of this technological advance, we propose to investigate the neural and genetic basis of cold sensation in C. elegans, a popular genetic model organism widely used for the study of sensory perception. To do so, we will use a multidisciplinary approach combining behavioral, genetic, calcium imaging, and electrophysiological analyses. As thermosensory mechanisms particularly those involving thermosensitive channels/receptors tend to be evolutionarily conserved, our work will provide novel insights into the mechanisms underlying cold sensation in mammals and related neurological and metabolic disorders.