The Cellular and Molecular Basis of Direction Selectivity of Aδ-LTMRs

The perception of touch, including the direction of stimulus movement across the skin, begins with activation of low-threshold mechanosensory neurons (LTMRs) that innervate the skin. Here, we show that murine A delta-LTMRs are preferentially tuned to deflection of body hairs in the caudal-to-rostral direction. This tuning property is explained by the finding that A delta-LTMR lanceolate endings around hair follicles are polarized; they are concentrated on the caudal (downward) side of each hair follicle. The neurotrophic factor BDNF is synthesized in epithelial cells on the caudal, but not rostral, side of hair follicles, in close proximity to A delta-LTMR lanceolate endings, which express TrkB. Moreover, ablation of BDNF in hair follicle epithelial cells disrupts polarization of A delta-LTMR lanceolate endings and results in randomization of A delta-LTMR responses to hair deflection. Thus, BDNF-TrkB signaling directs polarization of A delta-LTMR lanceolate endings, which underlies direction-selective responsiveness of A delta-LTMRs to hair deflection.