Topographically distinct epidermal nociceptive circuits revealed by axonal tracers targeted to Mrgprd

The brain receives sensory input from diverse peripheral tissues, including the skin, the body's largest sensory organ. Using genetically encoded axonal tracers expressed from the Mrgprd locus, we identify a subpopulation of nonpeptidergic, nociceptive neurons that project exclusively to the skin, and to no other peripheral tissue examined. Surprisingly, Mrgprd(+) innervation is restricted to the epidermis and absent from specialized sensory structures. Furthermore, Mrgprd(+) fibers terminate in a specific layer of the epidermis, the stratum granulosum. This termination zone is distinct from that innervated by most CGRP(+) neurons, revealing that peptidergic and nonpeptidergic epidermal innervation is spatially segregated. The central projections deriving from these distinct epidermal innervation zones terminate in adjacent laminae in the dorsal spinal cord. Thus, afferent input from different layers of the epidermis is conveyed by topographically segregated sensory circuits, suggesting that at least some aspects of sensory information processing may be organized along labeled lines.