History of Microglia.

The term 'microglia' was first introduced into the scientific literature a century ago. The various eras of microglial research have been defined not only by the number of reports subsequently generated but, more critically, also by the concepts that have shaped our present-day views and understanding of microglia. Key methods, technologies, and models, as well as seminal discoveries made possible through their deployment have enabled breakthroughs, and now pave the way for lines of investigation that could not have been anticipated even a decade ago. Advances in our understanding of the microglial origin, forms, and functions have relied fundamentally on parallel developments in immunology. As the 'neuro-immune' cells of the brain, microglia are now under the spotlight in various disciplines. This chapter surveys the gradual processes and precipitous events that helped form ideas concerning the developmental origin of microglia and their roles in health and disease. It first covers the dawning phase during which the early pioneers of microglial research discovered cellular entities and already assigned functions to them. Following a recess period, the 1960s brought about a renaissance of active interest, with the development of tools and models-and fundamental notions on microglial contributions to central nervous system (CNS) pathologies. These seminal efforts laid the foundation for the awakening of a sweeping research era beginning in the 1980s and spurred on by a blast of immunological discoveries. Finally, this chapter stresses the advancements in molecular, genetic, and imaging approaches to the study of microglia with the turn of the millennium, enabling insights into virtually all facets of microglial physiology. Moving forward, it is clear that the future holds substantial promise for further discoveries. The next epoch in the history of microglial research has just begun.