Role of astrocytes in synapse formation and maturation.

Astrocytes are the most abundant glial cells in the mammalian brain and directly participate in the proper functioning of the nervous system by regulating ion homeostasis, controlling glutamate reuptake, and maintaining the blood-brain barrier. In the last two decades, a growing body of work also identified critical roles for astrocytes in regulating synaptic connectivity. Stemming from the observation that functional and morphological development of astrocytes occur concurrently with synapse formation and maturation, these studies revealed that both developmental processes are directly linked. In fact, astrocytes both physically contact numerous synaptic structures and actively instruct many aspects of synaptic development and function via a plethora of secreted and adhesion-based molecular signals. The complex astrocyte-to-neuron signaling modalities control different stages of synaptic development such as regulating the initial formation of structural synapses as well as their functional maturation. Furthermore, the synapse-modulating functions of astrocytes are evolutionarily conserved and contribute to the development and plasticity of diverse classes of synapses and circuits throughout the central nervous system. Importantly, because impaired synapse formation and function is a hallmark of many neurodevelopmental disorders, deficits in astrocytes are likely to be major contributors to disease pathogenesis. In this chapter, we review our current understanding of the cellular and molecular mechanisms by which astrocytes contribute to synapse development and discuss the bidirectional secretion-based and contact-mediated mechanisms responsible for these essential developmental processes.