Investigating the role of microglia in shaping dorsal horn pain circuitry during normal development and after early postnatal injury (360G-Wellcome-109006_Z_15_A)

The neonatal CNS is highly responsive to noxious stimulation and early pain exposure, such as neonatal surgery or routine clinical procedures, cause persistent changes in somatosensory processing. It has been therefore been proposed that early life pain experience may determine adult pain sensitivity. Thus, an understanding of the postnatal development of the somatosensory and nociceptive system, and how it is influenced by early pain experience is an important neurobiological question. This project focusses upon developing nociceptive circuits within the dorsal horn of the mouse spinal cord and the interaction between microglia and neurons in this process. I plan to investigate how microglia shape nociceptive synaptic connections during normal postnatal development and their role in altering nociceptive circuitry after early life injury. The following questions will be addressed How do nociceptive and tactile afferents become structurally and functionally organized in the postnatal dorsal horn (dorsal horn sensory connectome)? What role do microglia play in the development of dorsal horn sensory connections under normal conditions and after neonatal injury? How do microglia change over postnatal development under normal conditions and after neonatal injury? Is injury-induced priming of microglia due to changes in the dorsal horn environment, changes in microglial properties, or both?