Decoding natural astrocyte rhythms: dynamic actin waves result from environmental sensing by primary rodent astrocytes

Abstract

Astrocytes are key regulators of brain homeostasis, an important physiological process that includes but is not limited to buffering of extracellular K+, equilibrating osmotic gradients, regulating pH, uptake of neurotransmitters, and releasing growth factors - all of which are essential for proper cognitive function. While previous studies have revealed how specific molecular components of the astrocytic cytoskeleton affect the efficacy of these homeostatic processes, none have studied how homeostasis is linked to the excitable systems character of the cytoskeleton. As recently discovered, excitability of the actin cytoskeleton manifests in second-scale dynamic fluctuations and acts as a sensor of chemo-physical environmental cues. Here we find that homeostatic regulation may be more active than previously thought, involving the excitable dynamics of actin in certain subcellular regions, especially near the cell boundary. Our results further indicate that actin dynamics concentrates into "hotspot" regions that selectively respond to certain chemo-physical stimuli, specifically the homeostatic challenges of ion or water concentration increases. Substrate topography makes the actin dynamics of astrocytes weaker. Superresolution images demonstrate that surface topography is also associated with predominant perpendicular alignment of actin filaments near the cell boundary whereas flat substrates result in an actin cortex mainly parallel to the cell boundary. Additionally, co-culture with neurons increases both the probability of actin dynamics and the strength of hotspots. The excitable systems character of actin thus makes astrocytes direct participants in neural cell network dynamics.