Mrgprb4-lineage neurons indispensable in pressure induced pleasant sensation are polymodal

Pharmacogenetic activation of the Mas-related G-protein-coupled receptor b4 (Mrgprb4) neurons in the dorsal root ganglia is positively reinforcing, and these neurons can be activated by innocuous or noxious mechanical stimuli. However, direct evidence regarding the role of these neurons and how they encode diverse somatic inputs remains unclear. To address this, the mild pressure conditioned place preference (MP-CPP) was conducted to evaluate the indispensability of Mrgprb4-lineage neurons in the pleasantness caused by pressure. Mice without Mrgprb4-lineage neurons lost the preference for pressure. The number of Mrgprb4-lineage neurons activated by pressure was significantly higher than that of brush and pinch. The Ca²⁺ transients activated by pressure and brush were higher than that of pinch. Further analysis of co-activating mechano-thermosensitive neurons showed that pressure evoked higher fluorescence than that of 0°C and 43°C. In brief, Mrgprb4-lineage neurons are needed to transmit pleasant sensation and exhibit functional polymodality.