Top-down somatosensory control by spinally projecting S1 neurons

Pain expectation is known to influence pain perception, but the underlying neuronal mechanisms remain unclear. While the motor role of the corticospinal tract is well characterized, only recently was it established that the corticospinal neurons originating from the primary somatosensory cortex (S1-CSNs) specifically contact the sensory region of the spinal cord, providing top-down regulation of sensations including pain. S1-CSNs neurons are therefore ideally positioned to modulate spinal nociception based on sensory representations and expectations. To test whether S1-CSNs activity is modulated during the anticipation of future pain, we recorded calcium activity from single S1-CSNs neurons in freely moving mice carrying a miniature microscope while learning to expect a painful stimulus, i.e. an optogenetic transdermal stimulation of nociceptive fibers signaled by an auditory cue. We observed that S1-CSNs neurons activity gradually increases over pain expectation learning and overlap with neurons representing painful stimuli, thereby providing a sensory expectation signal to the spinal dorsal horn. Mice also responded stronger to signaled painful stimuli, suggesting priming of nociceptive processing. Finally, we show that S1-CSNs activity is necessary for pain response.