Activity-dependent plasticity of the NMDA-receptor fractional Ca2+ current

Ca2+, influx through NMDA receptors (NIVIDARs) 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 NMDAR 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 Ca2+ accumulation per unit of NMDA-R current in spines due to a reduction in the fraction of the NMDA-R current carried by Ca2+. Induction of depression of NMDA-R-mediated Ca2+ 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.