Astrocyte-Neuron Networks: A Multilane Highway of Signaling for Homeostatic Brain Function

Abstract

Research on glial cells over the past 30 years has confirmed the critical role of astrocytes in pathophysiological brain states. However, most of our knowledge about astrocyte physiology and of the interactions between astrocytes and neurons is based on the premises that astrocytes constitute a homogeneous cell type, without considering the particular properties of the circuits or brain nuclei in which the astrocytes are located. Therefore, we argue that more-sophisticated experiments are required to elucidate the specific features of astrocytes in different brain regions, and even within different layers of a particular circuit. Thus, in addition to considering the diverse mechanisms used by astrocytes to communicate with neurons and synaptic partners, it is necessary to take into account the cellular heterogeneity that likely contributes to the outcomes of astrocyte-neuron signaling. In this review article, we briefly summarize the current data regarding the anatomical, molecular and functional properties of astrocyte-neuron communication, as well as the heterogeneity within this communication.

Keywords: astrocytes; behavior; heterogeneity; neuron–glia signaling; synaptic plasticity.

Figure 1

Heterogeneity of astrocyte–neuron networks. Astrocytes are able to respond to different NTs, cell types in different brain areas and under diverse patterns of stimulation. In turn, astrocytes modulate the activity of ion channels and neurotransmitter transporters in their membranes, but also release different active substances (so-called GTs, e.g., glutamate, gamma-aminobutyric acid (GABA), adenosine and D-serine, among others) that contribute to shape neuronal activity. However, it remains unclear whether the same or different astrocyte subtypes mediate these differential effects. The scheme illustrates recent evidence of the molecular and functional diversity of astrocytes that may underlie the outcomes of brain activity. In this context, single astrocytes can be affected by more than one physiological feature (represented as colored circles that connect to astrocytes), or subsets of astrocytes may show preferential links with particular physiological features, suggesting the existence of different astrocyte populations that exhibit specific properties (astrocyte color code). NTs, neurotransmitters; GTs, gliotransmitters; SS, somatosensory; PV, parvalbumin positive cells; SOM, somatostatin positive cells; VIP, vasoactive-intestinal peptide.