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Proprioception is our hidden "sixth sense" that provides sensory feedback on the position and movement of our bodies. Dysfunction of this feedback leads to profound gait and sensorimotor issues, as well as abnormal body development.In mammals, it is thought that proprioceptive neurons are found only in the periphery, in muscles, tendons and joints. However, the spinal cord is stretched and distorted in complex ways during body movements, and increasing evidence across species suggests that this can be detected by centrally-located proprioceptors as an additional source of motor feedback. However, this has never been tested in mammals.The goal of this project is to test this hypothesis directly in mice using a range of modern electrophysiological, imaging, and genetic techniques. Our preliminary data has identified a population of neurons in mouse spinal cord expressing the major mechanosensitive channel piezo2. This project will reveal the morphology and mechanical sensitivity of these neurons, and link their activity patterns to behaviorally-relevant movements of spinal cord. By genetically inhibiting piezo2 centrally, we will also assess the importance of intraspinal proprioceptors for motor control and development of the spine.Piezo2 mutations cause several debilitating diseases affecting motor control. Therefore, a deeper understanding of central, piezo2-expressing neurons may lead to new ways of understanding and ultimately treating diseases of the proprioceptive system.