Analysis of the functional states of an astrocyte syncytium

Abstract

In the central nervous system (CNS), astrocytes are cytoplasmically interconnected through specialized conduit proteins, called gap junctions. This establishes a syncytial network that runs across the entire brain. Because of this unique anatomic characteristic, the still mysterious function of astrocytes, particularly in the adult brain, is likely hidden within this syncytial network. Recent studies show that a strong electrical coupling is a system-wide feature of astrocyte networks, which enables astrocytes to constantly equalize their membrane potentials so that a syncytial isopotentiality can be achieved. Functionally, syncytial isopotentiality coordinates the individual astrocytes into a functional system in brain homeostasis. Dysregulated extracellular K+ concentration impairs neuronal excitability and synaptic transmission. Under syncytial isopotentiality, the homeostatic regulation of extracellular K+ can be performed with far greater efficacy than previously thought. In this chapter, this newly appreciated mechanism that governs the operation of astrocyte network will be introduced. A new functional readout concerning the functional state of an astrocyte network and its application will be described. Second, a new model system, freshly dissociated astrocyte miniature syncytium, will be introduced for the quantitative analysis of astrocyte syncytial network function. Third, a computational model will be introduced. A combination of these can be powerfully applied to decipher the dynamic change in the coupling strength of an astrocyte syncytium as well as astrocyte-neuron crosstalk at system levels. This new method also has a great potential to be used to identify a causal relationship between an impaired astrocyte network function and the disease under investigation. Overall, a novel approach described in this chapter allows examination of astrocyte function at the network level in the healthy and diseased brain.