SYNCHRONIZATION OF NEURONAL-ACTIVITY PROMOTES SURVIVAL OF INDIVIDUAL RAT NEOCORTICAL NEURONS IN EARLY DEVELOPMENT

Neural activity is thought to play a significant role during the devel opment of the cerebral cortex. In this study, we examined the effects of global activity block or enhancement and the effects of patterned f iring on the ability of cultured rat neocortical neurons to survive du ring the second week in vitro, beyond the beginning of synaptogenesis. Blockade of neuronal activity by adding tetrodotoxin (TTX) and increa sing magnesium concentration in the medium strongly reduced the surviv al of cortical cells. Increasing neuronal activity by raising the exte rnal potassium concentration significantly improved the survival of co rtical neurons. We postulated that in a developing neuronal network th e survival of nerve cells is regulated by synaptically mediated events that involve changes in the intracellular calcium concentration. To e xamine this question further, we monitored the activity of the develop ing network by optically recording the intracellular calcium signals o f many neurons simultaneously. These recordings show that in low magne sium neocortical neurons express synchronized oscillation of their int racellular calcium concentration. The ability of a network to synchron ize the changes in intracellular calcium of multiple cells appeared gr adually during the second week in culture, paralleled by both an incre ase in the synaptic density and a decline in the number of surviving n eurons. By examining the fate of identified cells several days after a recording session, we found that those nerve cells that were co-activ ated with other neurons had a significantly higher chance to survive t han cells that did not participate in synchronized events. These exper iments demonstrate that during early cortical network development cort ical neurons show synchronized firing activity and that the survival o f neurons is at least partially dependent on this pattern of neuronal activity.