Cutaneous Touch and Piezo2-Mediated Mechanotransduction Decline Throughout Mouse Maturation Until Adulthood

It is well-known that the age of studied animals has a profound impact on experimental outcomes in animal-basedresearch. In mice, age influences molecular, morphological, physiological, and behavioral parameters, in particularduring rapid postnatal growth and maturation until adulthood (at 12 weeks of age). Despite this knowledge, mostbiomedical studies use a wide-spanning age range between 5 to 12 weeks raising concerns about reproducibilityand potential masking of relevant age-differences. Here, using mouse behavior and electrophysiology in cultureddorsal root ganglia (DRG), we reveal a previously overlooked decline in behavioral cutaneous touch sensitivity andPiezo2-mediated mechanotransduction in vitro during mouse maturation but not thereafter. Consistent with thesefunctional data we identify distinct transcript changes in individual Piezo2-expressing mechanosensitive DRGneurons by combining electrophysiology with single-cell RNA-sequencing (patch-seq). Taken together, our studyemphasizes the need for accurate age-matching and uncovers hitherto unknown maturational plasticity incutaneous touch on the behavioral, transductional, and molecular level.