2020 Theses Doctoral

Dynamics of touch-receptor plasticity in the mammalian peripheral nervous system

Clary, Rachel Cecelia

Somatosensory neurons densely innervate skin, our largest sensory organ. Adult skin continually remodels throughout the lifespan to maintain a protective barrier for our bodies. How sensory neurons maintain their peripheral endings in the face of continual turnover of their target tissue is not well understood. To address this gap in knowledge, I analyzed the temporal dynamics and mechanisms of structural plasticity of touch receptors in healthy adult skin. My studies focused on the terminals of Merkel-cell afferents in mouse touch domes. These two-part touch receptors comprise epithelial Merkel cells innervated by branching axons of fast-conducting sensory neurons. I show that Merkel cells and their afferents are structurally plastic over the course of hair growth in adults. These two components simplify during active hair growth, with fewer terminal neurites and fewer Merkel cells per touch dome at this stage compared with other phases of hair growth. Merkel-cell removal was observed with multiple molecular markers. Additionally, mice showed diminished touch-evoked behavior during hair growth compared with follicle quiescence. Next, I showed that Sarm1, a key effector of Wallerian degeneration, is not required for structural plasticity of Merkel cell-neurite complexes in young adulthood. Finally, I developed a technique to perform time-lapse in vivo imaging of identified Merkel cells and afferent terminals over the course of a month. These structures were highly plastic, with afferent terminals undergoing frequent growth and regression, as well as both Merkel cells and terminal branches being added or removed. Together, these studies reveal that peripheral nerve terminals undergo a previously unsuspected amount of structural plasticity in healthy tissue.