Primary afferent axons must project accurately to their appropriate central targets to provide the template for the highly ordered somatotopic representations in the vertebrate brain. The research proposed will provide new information regarding the mechanisms underlying these proceses by answering the folowing questions: 1) Do sensory ganglioon cells or their central targets possess intrinsic specificities that guide the accurate primary afferent innervation of the brain during fetal life? We will address this question in two ways. We will describe the normal development of the primary afferent innervation of the spinal cord, and V, cuneate, and gracile nuclei using lipophilic dyes. If peripheral information is necessary for the orderly primary afferent innervation of the central nervous system, sensory gandlion cells must reach their peripheral targets prior to the development of ordered central projections. In second series of in vitro experiments, we will harvest both V ganglion and dorsal root ganglion (DRG) cells prior to the a ge at which they innervate either their peripheral or central targets and cocultured them with """"""""virgin"""""""" brainstem tissue. If eitehr the primary afferent neurons or their central targets are intrinsically specified, appropriate primary afferent projections should develop in vitro. 2) Does contact with the periphery provide asons with a signal that allows them to select appropriate central targets? If peripherally derived information is necessary and sufficient for appropriately targeted central primary afferent projections, elimination of temporal and spatial factors present in vivo should not cause a loss of primary afferent specificity. Conversely, and manipulation that deprives primary afferents of peripherally derived information should alter their central targeting. We will address this question in two experiments. First, we will leave sensory ganglion cells in contact with their peripheral t argets and co- culture these explants with virgin brainstem tissue. If peripheral contacts are sufficient to specify the central projections of sensory ganglion cells, the axons of these neurons whould select appropriate central targets. In a second in vivo experiment, we will deprive lumbar primary afferents of their normal targets in the hindlimb prior to the a ge at which they innervate this structure. If normal peripheral contracts are necessary fro the accurate central targeting of sensory axons, the fibers from these cells should not develop their normal central projections. 3) Does primary afferent innervation specify central compartments? We will address this question in two ways. We will ablate subsets of primary afferent in vivo b efore or a fter the age at which they have reached their central targets and then determine whether the deafferented central compartments will accept foreign innervation. In a second set of in vitro experiments, we will harvest portions of the brainstem before or after they have been innervated by their normal complement of primary afferents and then co-culture them with either appropriate or inappropriate sensory ganglion cells.
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