The dissertation by Sharon E. Haynes, titled "The P2Y12 receptor regulates microglial activation by extracellular nucleotides," explores the role of the P2Y12 receptor in microglial activation and chemotaxis. Microglia, the primary immune cells of the central nervous system (CNS), are activated following injury to migrate towards sites of damage. The study demonstrates that microglia from mice lacking the G1-coupled P2Y12 receptor exhibit normal baseline motility but fail to polarize, migrate, or extend processes towards nucleotides in vitro and in vivo. In P2ry12-/- mice, microglia show diminished directional branch extension towards sites of cortical damage. Additionally, P2Y12 expression is robust in the resting state but dramatically reduced after microglial activation. These findings suggest that P2Y12 is a key receptor mediating nucleotide-induced microglial chemotaxis during early stages of CNS injury. The dissertation also discusses the pharmacology of P2Y12 and its relationship with other purinergic receptors, particularly P2Y13, and provides insights into the functional significance of P2Y12 in microglial biology.The dissertation by Sharon E. Haynes, titled "The P2Y12 receptor regulates microglial activation by extracellular nucleotides," explores the role of the P2Y12 receptor in microglial activation and chemotaxis. Microglia, the primary immune cells of the central nervous system (CNS), are activated following injury to migrate towards sites of damage. The study demonstrates that microglia from mice lacking the G1-coupled P2Y12 receptor exhibit normal baseline motility but fail to polarize, migrate, or extend processes towards nucleotides in vitro and in vivo. In P2ry12-/- mice, microglia show diminished directional branch extension towards sites of cortical damage. Additionally, P2Y12 expression is robust in the resting state but dramatically reduced after microglial activation. These findings suggest that P2Y12 is a key receptor mediating nucleotide-induced microglial chemotaxis during early stages of CNS injury. The dissertation also discusses the pharmacology of P2Y12 and its relationship with other purinergic receptors, particularly P2Y13, and provides insights into the functional significance of P2Y12 in microglial biology.