Activity-dependent plasticity of the NMDA-receptor fractional Ca2+ current.
Ca(2+) influx through NMDA receptors (NMDA-Rs) triggers synaptic plasticity, gene transcription, and cytotoxicity, but little is known about the regulation of NMDA-Rs themselves. We used two-photon glutamate uncaging to activate NMDA-Rs on individual dendritic spines in rat CA1 neurons while we measured NMDA-R currents at the soma and [Ca(2+)] changes in spines. Low-frequency uncaging trains induced Ca(2+)-dependent long-term depression of NMDA-R-mediated synaptic currents. Additionally, uncaging trains caused a reduction in the Ca(2+) accumulation per unit of NMDA-R current in spines due to a reduction in the fraction of the NMDA-R current carried by Ca(2+). Induction of depression of NMDA-R-mediated Ca(2+) influx required activation of NR2B-containing receptors. Receptors in single spines depressed rapidly in an all-or-none manner. These adaptive changes in NMDA-R function likely play a critical role in metaplasticity and in stabilizing activity levels in neuronal networks with Hebbian synapses.
Sobczyk
Aleksander
A
Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Svoboda
Karel
K
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology; D009415:Nerve Net / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D002118:Calcium