Phosphorylation-state-dependent regulation of NMDA receptor short-term plasticity modifies hippocampal dendritic Ca2+ transients.
N-methyl-D-aspartate (NMDA) receptor-mediated currents are enhanced by phosphorylation. We have investigated effects of phosphorylation-dependent short-term plasticity of NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) on the induction of long-term depression (LTD). We confirmed in whole cell clamped CA1 pyramidal neurons that LTD is induced by pairing stimulus protocols. However, after serine-threonine phosphorylation was modified by postsynaptic introduction of a protein phosphatase-1 (PP1) inhibitor, the same pairing protocol evoked long-term potentiation (LTP). We determined effects of modification of phosphatase activity on evoked NMDA EPSCs during LTD induction protocols. During LTD induction, using a protocol pairing depolarization to -40 mV and 0.5 Hz stimulation, NMDA receptor-mediated EPSCs undergo a short-term enhancement at the start of the protocol. In neurons in which PP1 activity was inhibited, this short-term enhancement was markedly amplified. We then investigated the effect of this enhancement on Ca(2+) entry during the start of the LTD induction protocol. Enhancement of NMDA receptor-mediated responses was accompanied by an amplification of induction protocol-evoked Ca(2+) transients. Furthermore, this amplification required synaptic activation during the protocol, consistent with an enhancement of Ca(2+) entry mediated by NMDA receptor activation. The sign of NMDA receptor-mediated long-term plasticity, whether potentiation or depression depends on the amplitude of the synaptic Ca(2+) transient during induction. We conclude that short-term phosphorylation-dependent plasticity of the NMDA receptor-mediated EPSCs contributes significantly to the effect of phosphatase inhibition on the subsequent induction of LTD or LTP.
Chatterjea
Debika
D
Department of Biological Sciences and Laboratory of Integrative Neuroscience, University of Illinois, Chicago, IL 60607, USA.
Hamid
Edaeni
E
Leonard
John P
JP
Alford
Simon
S
D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D003712:Dendrites / Q000378:metabolism* / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism* / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D009924:Organ Culture Techniques; D010766:Phosphorylation / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism* / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate