Highlights d Two distinct mechanisms underlie PSI of cutaneous afferents and tactile sensitivity d GABA A Rs underlie homotypic activity-dependent PSI of afferents d Small-diameter afferents also engage heterotypic NMDARdependent PSI d Presynaptic GABA A Rs, not NMDARs, are necessary for texture discrimination In Brief Zimmerman et al. define distinct neurotransmitter and circuit mechanisms that gate the flow of tactile sensory information from the periphery into the spinal cord and characterize their roles in tactile sensitivity and behaviors. SUMMARYPresynaptic inhibition (PSI) of primary sensory neurons is implicated in controlling gain and acuity in sensory systems. Here, we define circuit mechanisms and functions of PSI of cutaneous somatosensory neuron inputs to the spinal cord. We observed that PSI can be evoked by different sensory neuron populations and mediated through at least two distinct dorsal horn circuit mechanisms. Lowthreshold cutaneous afferents evoke a GABA A -receptor-dependent form of PSI that inhibits similar afferent subtypes, whereas small-diameter afferents predominantly evoke an NMDA-receptor-dependent form of PSI that inhibits large-diameter fibers. Behaviorally, loss of either GABA A receptors (GABA A Rs) or NMDA receptors (NMDARs) in primary afferents leads to tactile hypersensitivity across skin types, and loss of GABA A Rs, but not NMDARs, leads to impaired texture discrimination. Post-weaning age loss of either GABA A Rs or NMDARs in somatosensory neurons causes systemic behavioral abnormalities, revealing critical roles of two distinct modes of PSI of somatosensory afferents in adolescence and throughout adulthood.Supplemental Information includes seven figures and two videos and can be found with this article online at https://doi.