A Spinal Circuit That Transmits Innocuous Cool Sensations

Temperature information is precisely processed in the nervous system. While progress has been made in identifying molecular thermosensors in the periphery, the neural circuits that process temperature information in the central nervous system remain unknown. Here we have identified an essential node in the neural circuitry for innocuous cool sensations. We found that a population of excitatory interneurons co-expressing Calbindin1 and Lbx1 (Calb1Lbx1) in the dorsal horn of the spinal cord is activated by innocuous cool temperatures. Genetic ablation or silencing of spinal Calb1Lbx1 neurons causes loss of innocuous cool but not noxious cold sensations. Further Brainbow labeling with expansion microscopy and electrophysiology showed that a small cluster of spinal Calb1Lbx1 interneurons in lamina I and the outer layer of lamina II represents the cooling-transmission neurons. These neurons receive monosynaptic connections from TRPM8+ primary sensory neurons and amplify the activity of cool-sensitive spinoparabrachial projection neurons. Our findings reveal a microcircuit in the dorsal spinal cord that specifically transmits innocuous cool sensations.