Characterization of spinal cord lamina I projection neurons: electrophysiological responses to cutaneous stimuli

Sensory information, such as touch, temperature, pain, itch, and pressure, is critical to survival. The uncertainty about the basic functional organization of various sensory pathways makes it difficult to develop treatments for chronic pain (Kandel, 2013). Evidence suggests that chronic pain affects the local circuits in the spinal cord dorsal horn, where nociceptive information conducted by primary sensory afferents arrives (Todd, 2010). These local circuits are formed by interneurons that synapse onto the projection neurons (PNs) and provide modulation to somatosensory signals, yet how this modulation occurs remains uncertain. Using an electrophysiological recording system, the Semi-Intact Ex Vivo Preparation, we asked whether PNs receive selective inhibitory inputs based on their cutaneous response profiles. The connections between the skin, the spinal nerves, and the spinal cord of the Phox2a::Cre crossed mice were preserved during dissection (Hachisuka et al., 2016), then we obtained whole-cell patch clamp recording of PNs to observe their EPSCs and IPSCs in response to mechanical and thermal stimulation of the skin. Our results suggest that PNs receive selective inhibitory inputs that correlate with their cutaneous response profiles. Most cold-selective PNs did not receive direct inhibitory inputs, mechanical-selective PNs received mechanical inhibitory inputs, and polymodal neurons received diverse inhibitory inputs. These results are consistent with a previous study (Razlan et al., 2026), suggesting that cold sensation was mediated by a unique pathway. In short, PNs were selectively modulated by inhibitory inputs based on their functional subtypes. A larger sample is needed, and data collection is ongoing.