Structural and functional development of touch sensory neurons

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Our sense of touch is essential for our ability to perform fine manual tasks and for affective behaviors, and disruptions in tactile sensitivity can profoundly affect quality of life. Low-threshold mechanoreceptor (LTMR) neurons detect non-painful tactile stimuli in the periphery and transmit this information to the central nervous system (CNS). Our lab has produced genetic tools that enable visualization and functional manipulation of the major LTMR subtypes in the mouse, revealing that primary LTMR afferents transmit highly organized information about the nature and position of the touch stimulus they detect. However, the mechanisms that establish LTMR connectivity in the CNS to produce the functional organization of mechanosensory inputs remain unknown. In particular, the role of neural activity during LTMR morphogenesis, central targeting, and synaptogenesis has not been tested. The goal of my proposed research is to characterize the structural and functional development of LTMR neurons, and to test the role of activity in establishing organized patterns of LTMR connectivity in the CNS. Aim 1 will use genetic tools to characterize the acquisition of LTMR morphologies and central targeting patterns, as well as synapse formation between LTMRs and their CNS targets. In Aim 2 I will use electrophysiological recordings to monitor the maturation of functional response properties in LTMRs, and will generate genetic tools to investigate the role of neural activity during LTMR central targeting and synaptogenesis. Together, my proposed research will define how the circuits that process tactile stimuli are established to allow for the exquisite spatial and functional organization of somatosensory representations in the CNS. Understanding how touch circuits are assembled during development will guide research efforts aimed at promoting the regeneration of sensory axons following nerve damage in conditions of injury or disease, as well as the design of effective neural prosthetics to restore sensory function.