Lessons from in vivo imaging

Abstract

The first line of defense against injury or disease in the central nervous system (CNS) is through microglia. In the adult brain, microglia were long believed to stay in a dormant/resting state, activated only in the event of an insult to the brain. This view changed dramatically with the development of modern imaging techniques that allowed the study of microglial behavior in the intact brain over time to reveal the dynamic nature of their responses. In vivo imaging studies using two-photon microscopy revealed a previously unknown function for microglia: they continuously screen the intact brain parenchyma with their fine processes on a timescale of minutes. By doing so, they contact neuronal cell bodies, axons, dendrites, and dendritic spines and are believed to play a central role in sculpting neuronal networks during development, adulthood, and the normal aging process. Following acute trauma, or in neurodegenerative or neuroinflammatory diseases, microglial responses range from protective to harmful, underscoring the need to better understand their diverse roles in different pathological conditions. In this chapter we will introduce two-photon microscopy and compare the in vivo and in vitro imaging approaches for studying microglia. We will also discuss relevant mouse models available for in vivo imaging studies of microglia and review how such studies are constantly reshaping our understanding of the multifaceted role of microglia in the healthy and diseased CNS.