A major issue in understanding the development of central somatosensory circuitry is the lack of available markers that permit observation of the paths taken and choices made by individual classes of spinal sensory neurons between initial specification of neural identity, and the establishment of central connections. For this reason it also remains unclear which embryonic subsets of dorsal spinal neuron become those that subserve each distinct somatosensory function. Although many subsets of dorsal horn neuron have been delineated during differentiation and early migratory phases of development, there is a fundamental need to bridge the period when neurons can be identified according to their transcriptional signature and when they can be identified according to their functional circuitry. Methods are required that permit visualization of the synaptic connections between functional classes of DRG neurons and individual classes of dorsal horn neuron and allow us to determine where and how those dorsal horn neurons project centrally during development and in the adult. The recent demonstration that attenuated rabies virus can be directed to specific cell types in the mature nervous system and travel transsynaptically from sensory neurons in the periphery into target central neurons, provides a way to explore the development of the central somatosensory system, defining functional connections through the establishment of synapses, permitting the assignment of function to embryonically identified neurons and conferring a marking technique that allows visualization of the central paths forged y individual classes of dorsal horn neuron. The object of the research in this R21 is to develop methodology that will permit selective anterograde and retrograde transsynaptic tracing of developing somatosensory circuitry during development and to establish the techniques for general use in developing systems.
Somatic sensation is essential to our ability to navigate the world. Perception of touch, temperature, skin position and painful stimuli are all dependent on appropriate circuitry and is establishment during embryonic and perinatal development. Although many early properties of spinal neurons that mediate somatic sensation have been delineated it remains unclear which classes of embryonic neurons develop into which functionally distinct cell types in mature animals. To understand the development of functional subsets it is necessary to follow their synaptic development, to discover their functional connections and to assess how they navigate the developing CNS environment. We propose to develop tracing techniques in embryos that will identify synaptic partners of spinal somatosensory neurons as their circuitry develops in embryos. These approaches will have far reaching use in other developing neural systems. Moreover they will provide basic information that may be useful in the development of therapeutic approaches following spinal cord injury.
