The spread of Ras activity triggered by activation of a single dendritic spine

In neurons, individual dendritic spines isolate N- methyl- D- aspartate ( NMDA) receptor- mediated calcium ion ( Ca(2+)) accumulations from the dendrite and other spines. However, the extent to which spines compartmentalize signaling events downstream of Ca(2+) influx is not known. We combined two- photon fluorescence lifetime imaging with two- photon glutamate uncaging to image the activity of the small guanosine triphosphatase Ras after NMDA receptor activation at individual spines. Induction of long- term potentiation ( LTP) triggered robust Ca(2+)- dependent Ras activation in single spines that decayed in similar to 5 minutes. Ras activity spread over similar to 10 micrometers of dendrite and invaded neighboring spines by diffusion. The spread of Ras- dependent signaling was necessary for the local regulation of the threshold for LTP induction. Thus, Ca(2+)- dependent synaptic signals can spread to couple multiple synapses on short stretches of dendrite.