Dynamism of an Astrocyte In Vivo: Perspectives on Identity and Function

Abstract

Astrocytes are an abundant and evolutionarily conserved central nervous system cell type. Despite decades of evidence that astrocytes are integral to neural circuit function, it seems as though astrocytic and neuronal biology continue to advance in parallel to each other, to the detriment of both. Recent advances in molecular biology and optical imaging are being applied to astrocytes in new and exciting ways but without fully considering their unique biology. From this perspective, we explore the reasons that astrocytes remain enigmatic, arguing that their responses to neuronal and environmental cues shape form and function in dynamic ways. Here, we provide a roadmap for future experiments to explore the nature of astrocytes in situ.

Keywords: astrocyte; evolution; glia; identity; morphology; neural circuits; physiology.

Figure 1

Dynamism of a Dog on a Leash by Giacomo Balla from 1912. This painting provides a graphic analogy for astrocytes in a state of constant flux. These cells are often defined by their responses to the particular neural circuit in which they exist. Reproduced with permission from Albright-Knox Art Gallery.

Figure 2

Cellular identity as a balance between cell-autonomous cues and cell-extrinsic cues. In contrast to neurons, few transcription factors that define the astrocytes as a unique lineage have been identified. This raises the question of whether astrocyte molecular identity is primarily state dependent and thus responsive to changes in their local environment.

Figure 3

Schematic of the wide range of time scales for various basic neuronal (action potential, EPSP, IPSP, and calcium change in response to action potential using genetically encoded sensors) and astrocytic calcium events. Astrocyte calcium excitability tends to be slower than many neuronal events. Abbreviations: EPSP, excitatory post-synaptic potential; IPSP, inhibitory post-synaptic potential.

Figure 4

Schematic of the different possible types of morphological changes, including (a) full-scale, whole-cell branch retraction and (b) subtler changes in the astrocytic coverage of synapses. Pre- and post- refer to the pre- and post-synaptic cells. Both large-scale retraction (a) and smaller-scale synaptic coverage changes (b) can affect neuronal signaling, but these have not yet been explored in many brain regions.

Figure 5

Astrocytes across model organisms display extensive elaboration of fine branches. (a) Zebrafish radial glia in an adult dorsal telencephalon sparse labeled with a membrane-bound fluorescent reporter. Image courtesy of Marion Coolen and Laure Bally-Cuif, Institut Pasteur, Paris. (b) Third instar larval astrocytes in Drosophila ventral nerve cord: Astrocytes are blue and sparse labeled in red and green using twin-spot MARCM (mosaic analysis with a repressible cell marker). Image courtesy of Tobias Stork and Marc Freeman, Vollum Institute, Portland, Oregon. (c) Adult mouse cortical astrocytes tiling across cortical layers and sparse labeled in red and green using a confetti:hGFAPcre construct. Image by Kimberly Hoi and Anna Molofsky. (d) Single juvenile murine cortical astrocyte labeled with a membrane-bound fluorescent protein. Image by Kira Poskanzer. (e) Partially penetrant EAAT2-tdTomato BAC transgenic cortical astrocytes indicating fine process labeling and astrocyte-vascular contacts (98). Image by Michelle Cahill and Kira Poskanzer.