AAV1-Syn-FLPo

Innocuous mechanical stimuli acting on the skin are detected by sensory neurons, known as low-threshold mechanoreceptors (LTMRs). Here, researchers report the organizational properties of the cutaneous and central axonal projections of the five major hairy cutaneous LTMR subtypes. The researchers found that the axons of neurons in a specific LTMR class largely did not overlap with their cutaneous end organs, such as hair follicles, with Aβ's rapid adaptation to LTMR being the only exception. Individual neurons of each LTMR class generally do not overlap with their associated hair follicles, with the notable exception of C-LTMR, which exhibits multiple branches that redundantly innervate individual hair follicles. In the spinal cord, LTMR central projections exhibit craniocaudal elongation and medial compression compared with cutaneous innervation patterns, and these central projections also exhibit a fine degree of homotypic topographic adjacency. Thus, these findings reveal homotypic tiling of LTMR subtype axonal projections in hairy skin and remarkable spatial precision in spinal axon termination patterns, suggesting a somatotopically precise tactile encoding capability in the mechanosensory dorsal horn.

Here, the researchers injected AAV1-Syn-FlpO virus into different skin regions of LTMR-Cre or -CreER and dual recombinase reporter mice to evaluate the central projection patterns of individual neurons in each LTMR class. They observed that the central projections of C-LTMRs, Aδ-LTMRs, and Aβ RA-LTMRs innervating dorsal hairy skin consistently terminated in a more anterior position relative to the DRG where their cell bodies are located (Figure 1B), consistent with previous studies. This same pattern was observed for lumbar back and thigh hairy skininnervating neurons. In contrast, the central projections of LTMRs that innervate cervical or thoracic abdominal skin instead exhibited a bias in the caudal direction (Figure 1). These studies suggest that signals emanating from abdominal body region LTMRs must be conveyed to the brain via spinal cord projection neurons. Together, these findings reveal fundamental differences in the morphological and anatomical properties of LTMR central projections based on body region and the location of their cutaneous receptive fields.

Figure 1. LTMR central projection display morphological differences according to body region innervated. (Kuehn E D, et al., 2019)