Developing and mature synapses

Abstract

Microglia are the resident immune cells of the brain. As such, they rapidly detect changes in normal brain homeostasis and accurately respond by fine-tuning in a tightly regulated manner their morphology, gene expression, and functional behaviour. Depending on the nature of these changes, microglia can thicken and retract their processes, proliferate and migrate, release numerous signalling factors and compounds influencing neuronal physiology (e.g., cytokines and trophic factors), in addition to secreting proteases able to transform the extracellular matrix, and phagocytosing various types of cellular debris, etc. Because microglia also transform rapidly (on a time scale of minutes) during experimental procedures, studying these very special cells requires methods that are specifically non-invasive. The development of such methods has provided unprecedented insights, these past few years, into the roles of microglia during normal physiological conditions. In particular, transcranial two-photon in vivo imaging revealed that presumably resting microglia continuously survey the brain parenchyma with their highly motile processes, in addition to modulating their structural and functional interactions with neuronal circuits along the changes in neuronal activity and behavioural experience occurring throughout the lifespan. In this chapter, we will describe how surveillant microglia interact with synaptic elements, and modulate the number, maturation, function, and plasticity of synapses in the healthy developing, mature, and aging brain, with consequences on neuronal activity, learning and memory, and the behavioural outcome.