Characterisation of cold-selective lamina I spinal projection neurons

Skin cooling is detected by primary afferents that express the Trpm8 channel, but how this information is conveyed to the brain remains poorly understood. We have previously identified a population of lamina I projection neurons belonging to the anterolateral system (ALS) that receive numerous contacts from Trpm8-expressing primary afferents. Here, using a semi-intact somatosensory preparation, we show that these cells correspond to the cold-selective ALS neurons identified in previous physiological studies. We also confirm the presence of synapses from Trpm8 afferents onto these cells at the ultrastructural level. Based on our previous transcriptomic findings, we identify calbindin as a molecular marker, and show that this can be used to target the cold-selective ALS neurons for anterograde tracing studies. We provide evidence that they project to 3 brain regions that are associated with thermosensation: the rostralmost part of the lateral parabrachial area, the caudal part of the periaqueductal grey matter, and the ventral posterolateral nucleus of the thalamus. Our findings provide important insights into the organisation of neuronal circuits that underlie thermoregulation and the perception of cold stimuli applied to the skin.