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Science 321 (5885): 136-140

Copyright © 2008 by the American Association for the Advancement of Science

The Spread of Ras Activity Triggered by Activation of a Single Dendritic Spine

Christopher D. Harvey,1,2* Ryohei Yasuda,2,3*{dagger} Haining Zhong,1,2 Karel Svoboda1,2{dagger}

Abstract: 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.

{dagger} To whom correspondence should be addressed. E-mail: yasuda{at}, svobodak{at}

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