Multifarious astrocyte–neuron dialog in shaping neural circuit architecture

Astrocytes are multifaceted glial cell types that perform structural, functional, metabolic, and homeostatic roles in the brain. Recent studies have revealed mechanisms underlying the diversity of bidirectional communication modes between astrocytes and neurons – the fundamental organizing principle shaping synaptic properties at tripartite synapses. These astrocyte–neuron interactions are critical for the proper functioning of synapses and neural circuits. This review focuses on molecular mechanisms that direct these interactions, highlighting the versatile roles of multiple adhesion-based paths that likely modulate them, often in a context-dependent manner. It also describes how astrocyte-mediated processes go awry in certain brain disorders and provides a timely insight on the pivotal roles of astrocyte–neuron interactions in synaptic integrity and their relevance to understanding and treating neurological disorders.