The Spread of Ras Activity Triggered by Activation of a Single Dendritic Spine
Christopher D. Harvey,1,2*
Ryohei Yasuda,2,3*
Haining Zhong,1,2
Karel Svoboda1,2
In neurons, individual dendritic spines isolate N-methyl-D-aspartate (NMDA) receptor–mediated calcium ion (Ca2+) accumulations from the dendrite and other spines. However, the extent to which spines compartmentalize signaling events downstream of Ca2+ 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 Ca2+-dependent Ras activation in single spines that decayed in 
5 minutes. Ras activity spread over 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, Ca2+-dependent synaptic signals can spread to couple multiple synapses on short stretches of dendrite.
1 Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
2 Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
3 Neurobiology Department, Duke University Medical Center, Durham, NC 27710, USA.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: yasuda{at}neuro.duke.edu, svobodak{at}janelia.hhmi.org
