Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

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}neuro.duke.edu, svobodak{at}janelia.hhmi.org

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Centaurin-{alpha}1-Ras-Elk-1 Signaling at Mitochondria Mediates {beta}-Amyloid-Induced Synaptic Dysfunction.
E. M. Szatmari, A. F. Oliveira, E. J. Sumner, and R. Yasuda (2013)
J. Neurosci. 33, 5367-5374
   Abstract »    Full Text »    PDF »
Imaging Intracellular Signaling Using Two-Photon Fluorescent Lifetime Imaging Microscopy.
R. Yasuda (2012)
Cold Spring Harb Protoc 2012, pdb.top072090
   Abstract »    Full Text »    PDF »
Studying Signal Transduction in Single Dendritic Spines.
R. Yasuda (2012)
Cold Spring Harb Perspect Biol 4, a005611
   Abstract »    Full Text »    PDF »
Acousto-Optical Deflector-Based Patterned Ultraviolet Uncaging of Neurotransmitter for the Study of Neuronal Integration.
E. F. Civillico, S. Shoham, D. H. O'Connor, D. V. Sarkisov, and S. S.- H. Wang (2012)
Cold Spring Harb Protoc 2012, pdb.top070631
   Abstract »    Full Text »    PDF »
NMDA Receptor-Dependent Long-Term Potentiation and Long-Term Depression (LTP/LTD).
C. Luscher and R. C. Malenka (2012)
Cold Spring Harb Perspect Biol 4, a005710
   Abstract »    Full Text »    PDF »
I{kappa}B Kinase/Nuclear Factor {kappa}B-Dependent Insulin-Like Growth Factor 2 (Igf2) Expression Regulates Synapse Formation and Spine Maturation via Igf2 Receptor Signaling.
M. J. Schmeisser, B. Baumann, S. Johannsen, G. F. Vindedal, V. Jensen, O. C. Hvalby, R. Sprengel, J. Seither, A. Maqbool, A. Magnutzki, et al. (2012)
J. Neurosci. 32, 5688-5703
   Abstract »    Full Text »    PDF »
Synaptic evidence for the efficacy of spaced learning.
E. A. Kramar, A. H. Babayan, C. F. Gavin, C. D. Cox, M. Jafari, C. M. Gall, G. Rumbaugh, and G. Lynch (2012)
PNAS 109, 5121-5126
   Abstract »    Full Text »    PDF »
Developmental regulation of the late phase of long-term potentiation (L-LTP) and metaplasticity in hippocampal area CA1 of the rat.
G. Cao and K. M. Harris (2012)
J Neurophysiol 107, 902-912
   Abstract »    Full Text »    PDF »
Locally Synchronized Synaptic Inputs.
N. Takahashi, K. Kitamura, N. Matsuo, M. Mayford, M. Kano, N. Matsuki, and Y. Ikegaya (2012)
Science 335, 353-356
   Abstract »    Full Text »    PDF »
Stable Learning in Stochastic Network States.
S. El Boustani, P. Yger, Y. Fregnac, and A. Destexhe (2012)
J. Neurosci. 32, 194-214
   Abstract »    Full Text »    PDF »
Automated Analysis of Spines from Confocal Laser Microscopy Images: Application to the Discrimination of Androgen and Estrogen Effects on Spinogenesis.
H. Mukai, Y. Hatanaka, K. Mitsuhashi, Y. Hojo, Y. Komatsuzaki, R. Sato, G. Murakami, T. Kimoto, and S. Kawato (2011)
Cereb Cortex 21, 2704-2711
   Abstract »    Full Text »    PDF »
Calcium Signaling in Synapse-to-Nucleus Communication.
A. M. Hagenston and H. Bading (2011)
Cold Spring Harb Perspect Biol 3, a004564
   Abstract »    Full Text »    PDF »
A Kinase Anchor Protein 150 (AKAP150)-associated Protein Kinase A Limits Dendritic Spine Density.
Y. Lu, X.-m. Zha, E. Y. Kim, S. Schachtele, M. E. Dailey, D. D. Hall, S. Strack, S. H. Green, D. A. Hoffman, and J. W. Hell (2011)
J. Biol. Chem. 286, 26496-26506
   Abstract »    Full Text »    PDF »
The 64th Symposium of the Society for General Physiologists: optogenetics and superresolution microscopy take center stage.
G. C. R. Ellis-Davies and E. N. Pugh Jr. (2011)
J. Gen. Physiol. 138, 1-11
   Full Text »    PDF »
Photon counting, censor corrections, and lifetime imaging for improved detection in two-photon microscopy.
J. D. Driscoll, A. Y. Shih, S. Iyengar, J. J. Field, G. A. White, J. A. Squier, G. Cauwenberghs, and D. Kleinfeld (2011)
J Neurophysiol 105, 3106-3113
   Abstract »    Full Text »    PDF »
Two-Photon Uncaging Microscopy.
M. Matsuzaki and H. Kasai (2011)
Cold Spring Harb Protoc 2011, pdb.prot5620
   Abstract »    Full Text »    PDF »
Ras and Rap Signaling in Synaptic Plasticity and Mental Disorders.
R. L. Stornetta and J. J. Zhu (2011)
Neuroscientist 17, 54-78
   Abstract »    PDF »
Regulation of the Postsynaptic Cytoskeleton: Roles in Development, Plasticity, and Disorders.
T. Svitkina, W.-H. Lin, D. J. Webb, R. Yasuda, G. A. Wayman, L. Van Aelst, and S. H. Soderling (2010)
J. Neurosci. 30, 14937-14942
   Abstract »    Full Text »    PDF »
Hippocampal Dysfunction and Cognitive Impairments Provoked by Chronic Early-Life Stress Involve Excessive Activation of CRH Receptors.
A. S. Ivy, C. S. Rex, Y. Chen, C. Dube, P. M. Maras, D. E. Grigoriadis, C. M. Gall, G. Lynch, and T. Z. Baram (2010)
J. Neurosci. 30, 13005-13015
   Abstract »    Full Text »    PDF »
AMPA receptors are exocytosed in stimulated spines and adjacent dendrites in a Ras-ERK-dependent manner during long-term potentiation.
M. A. Patterson, E. M. Szatmari, and R. Yasuda (2010)
PNAS 107, 15951-15956
   Abstract »    Full Text »    PDF »
A Novel Postsynaptic Mechanism for Heterosynaptic Sharing of Short-Term Plasticity.
K. J. Reissner, L. Pu, J. H. Schaffhausen, H. D. Boyle, I. F. Smith, I. Parker, and T. J. Carew (2010)
J. Neurosci. 30, 8797-8806
   Abstract »    Full Text »    PDF »
Sensory Experience and Cortical Rewiring.
S. J. Barnes and G. T. Finnerty (2010)
Neuroscientist 16, 186-198
   Abstract »    PDF »
Molecular and Cellular Approaches to Memory Allocation in Neural Circuits.
A. J. Silva, Y. Zhou, T. Rogerson, J. Shobe, and J. Balaji (2009)
Science 326, 391-395
   Abstract »    Full Text »    PDF »
2008: Signaling Breakthroughs of the Year.
E. M. Adler (2009)
Science Signaling 2, eg1
   Abstract »    Full Text »    PDF »
Computational Implications of Cooperative Plasticity Induction at Nearby Dendritic Sites.
K. Morita (2009)
Science Signaling 2, pe2
   Abstract »    Full Text »    PDF »
A genetically encoded fluorescent sensor of ERK activity.
C. D. Harvey, A. G. Ehrhardt, C. Cellurale, H. Zhong, R. Yasuda, R. J. Davis, and K. Svoboda (2008)
PNAS 105, 19264-19269
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882