Touch comes of Age - Maturational Plasticity in Somatosensory Mechanosensation
von Niklas Michel
Datum der mündl. Prüfung:2019-06-14
Betreuer:Prof. Dr. Manuela Schmidt
Gutachter:Prof. Dr. Martin Göpfert
Gutachter:Prof. Dr. Luis A. Pardo
EnglischSomatosensory mechanosensation remains to be the least understood sensory system in vertebrates. It requires the activation of specialised neurons which innervate the skin and internal organs. A subset of these dorsal root ganglion neurons express Piezo2, which has recently been found to be the key player in the senses of touch and proprioception. This ion channel accomplishes mechanotransduction - the conversion of mechanical stimuli into electrical signals. Tactile sensitivity in humans is subject to regulation and ageing processes. Moreover, it is altered in diverse pain conditions and autism spectrum disorders. In this line, this thesis sets out to investigate whether tactile sensitivity changes with maturation and ageing in healthy mice. Strikingly, a significant and specific decrease of Piezo2-mediated mechanically-activated currents in dorsal root ganglion neurons of four- to twelve-week-old wild-type mice was found. Moreover, both glabrous and hairy skin mechanosensitivity were also found to decrease in these maturing mice by longitudinal testings. This plasticity in somatosensory mechanosensation has previously been unreported. It challenges the fields assumptions about mature physiology and poses an optimal model for studying the molecular underpinnings of age-dependent regulation of somatosensory mechanotransduction. In that regard, significant changes in the transcriptome of DRG neurons between four and twelve weeks of age were found. Piezo2 mRNA was found to contain a decreasing amount of exon 33. This alternative splicing was shown to decrease Ca2+ permeability and might partly explain the phenotype. Furthermore, by means of patch-seq - the combination of electrophysiology and single-cell RNA-seq - promising candidate genes were found to be maturationally regulated in a sensory neuron subtype-specific manner. The findings are discussed and put into perspective with regard to ageing, sensory restriction and the somatosensory research field.
Keywords: Somatosensation; Patch-clamp; Transcriptomics; Mouse behaviour; Maturation; Piezo2