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 (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 approximately 5 minutes. Ras activity spread over approximately 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.
Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
Christopher D
CD
Harvey
Ryohei
R
Yasuda
Haining
H
Zhong
Karel
K
Svoboda
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D049229:Dendritic Spines / Q000502:physiology*; D004058:Diffusion; D031541:Fluorescence Resonance Energy Transfer; D020690:GTPase-Activating Proteins / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D017774:Long-Term Potentiation; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses / Q000502:physiology*; D014162:Transfection; D018631:ras Proteins / Q000378:metabolism*
D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D016194:Receptors, N-Methyl-D-Aspartate; D011993:Recombinant Fusion Proteins; D018698:Glutamic Acid; D018631:ras Proteins; D002118:Calcium