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Supersensitive Ras activation in dendrites and spines revealed by two-photon fluorescence lifetime imaging.

Publication ,  Journal Article
Yasuda, R; Harvey, CD; Zhong, H; Sobczyk, A; van Aelst, L; Svoboda, K
Published in: Nat Neurosci
February 2006

To understand the biochemical signals regulated by neural activity, it is necessary to measure protein-protein interactions and enzymatic activity in neuronal microcompartments such as axons, dendrites and their spines. We combined two-photon excitation laser scanning with fluorescence lifetime imaging to measure fluorescence resonance energy transfer at high resolutions in brain slices. We also developed sensitive fluorescent protein-based sensors for the activation of the small GTPase protein Ras with slow (FRas) and fast (FRas-F) kinetics. Using FRas-F, we found in CA1 hippocampal neurons that trains of back-propagating action potentials rapidly and reversibly activated Ras in dendrites and spines. The relationship between firing rate and Ras activation was highly nonlinear (Hill coefficient approximately 5). This steep dependence was caused by a highly cooperative interaction between calcium ions (Ca(2+)) and Ras activators. The Ras pathway therefore functions as a supersensitive threshold detector for neural activity and Ca(2+) concentration.

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Published In

Nat Neurosci

DOI

ISSN

1097-6256

Publication Date

February 2006

Volume

9

Issue

2

Start / End Page

283 / 291

Location

United States

Related Subject Headings

  • ras Proteins
  • Rats
  • Photons
  • Patch-Clamp Techniques
  • Organ Culture Techniques
  • Neurology & Neurosurgery
  • Microscopy, Fluorescence
  • Microscopy, Confocal
  • Humans
  • Hippocampus
 

Citation

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Yasuda, R., Harvey, C. D., Zhong, H., Sobczyk, A., van Aelst, L., & Svoboda, K. (2006). Supersensitive Ras activation in dendrites and spines revealed by two-photon fluorescence lifetime imaging. Nat Neurosci, 9(2), 283–291. https://doi.org/10.1038/nn1635
Yasuda, Ryohei, Christopher D. Harvey, Haining Zhong, Aleksander Sobczyk, Linda van Aelst, and Karel Svoboda. “Supersensitive Ras activation in dendrites and spines revealed by two-photon fluorescence lifetime imaging.Nat Neurosci 9, no. 2 (February 2006): 283–91. https://doi.org/10.1038/nn1635.
Yasuda R, Harvey CD, Zhong H, Sobczyk A, van Aelst L, Svoboda K. Supersensitive Ras activation in dendrites and spines revealed by two-photon fluorescence lifetime imaging. Nat Neurosci. 2006 Feb;9(2):283–91.
Yasuda, Ryohei, et al. “Supersensitive Ras activation in dendrites and spines revealed by two-photon fluorescence lifetime imaging.Nat Neurosci, vol. 9, no. 2, Feb. 2006, pp. 283–91. Pubmed, doi:10.1038/nn1635.
Yasuda R, Harvey CD, Zhong H, Sobczyk A, van Aelst L, Svoboda K. Supersensitive Ras activation in dendrites and spines revealed by two-photon fluorescence lifetime imaging. Nat Neurosci. 2006 Feb;9(2):283–291.

Published In

Nat Neurosci

DOI

ISSN

1097-6256

Publication Date

February 2006

Volume

9

Issue

2

Start / End Page

283 / 291

Location

United States

Related Subject Headings

  • ras Proteins
  • Rats
  • Photons
  • Patch-Clamp Techniques
  • Organ Culture Techniques
  • Neurology & Neurosurgery
  • Microscopy, Fluorescence
  • Microscopy, Confocal
  • Humans
  • Hippocampus