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The Journal of Neuroscience, June 29, 2005, 25(26):6037-6046; doi:10.1523/JNEUROSCI.1221-05.2005

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Cellular/Molecular
NMDA Receptor Subunit-Dependent [Ca2+] Signaling in Individual Hippocampal Dendritic Spines

Aleksander Sobczyk,1,2 Volker Scheuss,1 and Karel Svoboda1

1Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, and 2Department of Physics, State University of New York at Stony Brook, Stony Brook, New York 11794

Ca2+ influx through synaptic NMDA receptors (NMDA-Rs) triggers a variety of adaptive cellular processes. To probe NMDA-R-mediated [Ca2+] signaling, we used two-photon glutamate uncaging to stimulate NMDA-Rs on individual dendritic spines of CA1 pyramidal neurons in rat brain slices. We measured NMDA-R currents at the soma and NMDA-R-mediated [Ca2+] transients in stimulated spines ({Delta}[Ca2+]). Uncaging-evoked NMDA-R current amplitudes were independent of the size of the stimulated spine, implying that smaller spines contain higher densities of functional NMDA-Rs. The ratio of {Delta}[Ca2+] over NMDA-R current was highly variable (factor of 10) across spines, especially for small spines. These differences were not explained by heterogeneity in spine sizes or diffusional coupling between spines and their parent dendrites. In addition, we find that small spines have NMDA-R currents that are sensitive to NMDA-R NR2B subunit-specific antagonists. With block of NR2B-containing receptors, the range of {Delta}[Ca2+]/NMDA-R current ratios and their average value were much reduced. Our data suggest that individual spines can regulate the subunit composition of their NMDA-Rs and the effective fractional Ca2+ current through these receptors.

Key words: NMDA receptor; NR2B subunit; dendritic spines; two-photon; [Ca2+] imaging; glutamate uncaging


Received March 29, 2005; revised May 12, 2005; accepted May 13, 2005.




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