Neuronal death induced by endogenous extracellular ATP in retinal cholinergic neuron density control

The precise assembly of neuronal circuits requires that the correct number of pre- and postsynaptic neurons form synaptic connections. Neuronal cell number is thus tightly controlled by cell death during development. Investigating the regulation of cell number in the retina we found an ATP gated mechanism of neuronal death control. By degrading endogenous extracellular ATP or blocking the P2X(7) ATP receptors we found that endogenous extracellular ATP triggers the death of retinal cholinergic neurons during normal development. ATP-induced death eliminates cholinergic cells too close to one another, thereby controlling the total number, the local density and the regular spacing of these neurons.