Distinct Proprioceptive Pathways and their Specific Contributions to Motor Control
1 University Hospital Cologne
Our perception of body position and motion is critical for coordinating muscle contractions into meaningful movements. Cell bodies of proprioceptive neurons reside in dorsal root ganglia (DRG) where they send projections bidirectionally to the periphery to sense the current state of muscles and to the central nervous system to continually update ourselves on body position. Without these neurons, individuals are left unable to coordinate movements leaving them incapable of performing even simple tasks such as standing upright, let alone targeted movements. While distinct classes of proprioceptive neurons have been identified, previous tools have prevented the specific targeting of the unique classes for understanding their functional contribution to motor behavior or how they are integrated into the central nervous system. However, recent single cell RNA sequencing studies on proprioceptors have shown that they may be more heterogeneous than previously thought. This leaves a necessity to generate a refined map and understanding of proprioceptive subtypes and how they work together to allow us to perceive where our body is and how it may be moving. Utilizing these recent discoveries, we have generated Runx3DreO mice, carrying a knock in allele in which DreO recombinase expression is driven by the endogenous Runx3 promoter. Characterization of this new line showed labeled cells in the DRGs that presented the main hallmarks of proprioceptors. These large and myelinated neurons co-express Parvalbumin with one axon extending towards the periphery (muscle), and one centrally to the dorsal horn of the spinal cord and/or the dorsal column nuclei in the brainstem. Further, confirming the specificity of this line, we observed no labeling of other neuronal populations across brain regions, only microglia. Runx3Dre can be used with existing Cre and Flp recombinase lines for precise intersectional genetic targeting. With this newly generated mouse line, we have designed a novel strategy to target specific proprioceptive subtypes so that we can a) visualize their circuitry and projection targets and b) functionally characterize their individual roles in motor control. In doing so we will generate a blueprint for designing better therapies for those afflicted with spinal cord injuries or proprioceptive impairments.