The multiple scales of astrocytic functional units

Astrocytes modulate brain processes such as neurotransmitter signaling, ion homeostasis, vascular tone, metabolism and synaptic transmission, and serve a critical role in complex brain functions. However, it remains unclear on which spatial scales these functions are organized in astrocytes and their networks: for instance, whether astrocytic interactions with neurons are organized into units at the level of individual perisynaptic processes and synapses, astrocytic domains covering synapse populations, or astrocytic networks controlling local neuronal circuits. Here we analyze astrocytic morphological features and molecular heterogeneity to define the multiple spatial scales on which astrocytes operate. We further discuss evidence regarding their intracellular and intercellular signaling, their role in neurotransmitter homeostasis and their neurotransmitter-mediated dialog with neurons, supporting the existence of astrocytic functional units with distinct spatial scales. We propose that astrocytes constitute a multilayered system of functional units that operate across multiple spatial scales, thereby increasing the degrees of freedom in brain information processing.