Spontaneous Calcium Transients in Cultured Cortical Networks During Development

Spontaneous neuronal activity plays an important role in the development of the brain. Developmental changes in the spontaneous activity pattern of neuronal networks in vitro have been extensively studied by using the microelectrode array (MEA) recording system. However, little is known about the transition of spontaneous intracellular calcium dynamics, and the relationship between calcium transients and electrical activity during development. In the present paper, we carry out simultaneous recording of spontaneous electrical activity and intracellular calcium transients of rat cortical networks cultured on MEA. In one-week cultures, periodic synchronized bursts are observed and are followed by synchronized calcium transients. In three-week cultures, synchronized calcium transients are rarely observed despite the presence of highly complicated synchronized activity. Between these two states, in two-week cultures, slow, radial propagation of calcium waves independent of electrical activity is observed. Pharmacological treatments with the purinergic receptor antagonist suramin and gap junction blocker 18-beta glycyrrhetinic acid reveal that the spontaneous radial calcium waves are mediated by the astrocytic network, and suggest that the astrocytic calcium waves can influence the electrical firing patterns of networks by locally affecting neuronal signaling. These results indicate that the various dynamics of intracellular calcium transients regulate the network maturation processes.