A neural-glial network for modeling spreading depression in cortex

Background and model Spreading depression (SD) is a propagating wave of transient neuronal hyperexcitability followed by complete electrical silence that moves slowly (15–50 μm s-1) across grey matter in the central nervous system; it has been implicated in a number of brain disorders [1]. SD involves a massive redistribution of ions (K+, Na+, Ca2+, Cl -) between intracellular and extracellular compartments. Although first described over 60 years ago, it is still not well understood [1]. SD is accompanied by large increases in extracellular ATP, which is a principal means of transmission between astrocytes; also, ATP waves in astrocyte networks move at speeds comparable to SD [2,3]. These facts, and other evidence [4], strongly suggest that astrocytes play an important role in SD. We have constructed a mathematical model in which SD is driven by the effects of astrocyte waves interacting with waves of glutamate released from neurons and astrocytes (Figure 1). The detailed equations and computational methods were based on our previous work on glial and neural-glial systems [2,3,5]. All major ion channels, exchangers and pumps were included in both neurons and astrocytes (cf. [6]).