Activity-dependent survival of neurons in culture: a model of slow neurodegeneration

Central neurons express persistent spontaneous electrical network activity both in the developing brain in vivo as well as in dissociated cultures. This electrical activity is important for the formation of connections among neurons, and for their survival. Prolonged suppression of the spontaneous activity using the sodium channel blocker tetrodotoxin (TTX) causes the death of the cultured neurons. In the present study, we investigated molecular mechanisms that may underlie the activity-suppressed slow degeneration of cortical neurons in culture. Already after 6-7 days of exposure to TTX, neurons begin to express apoptotic vacuoles and shrunken dendrites. Eventually, neurons activate p53, caspase-3 and BAX, hallmarks of neuronal apoptosis, before they die. This death is restricted to neurons, and no parallel process is seen in glial cells that co-exist in the culture. These experiments may lead to a better understanding of slow neuronal death, akin to that found in neurodegenerative diseases of the brain.