NMDA receptor 2 (NR2) C-terminal control of NR open probability regulates synaptic transmission and plasticity at a cerebellar synapse.
The C-terminal domain of NMDA receptor 2 (NR2) subunits has been proposed to play a critical role in regulating NMDA receptor localization and function in postsynaptic densities. However, the mechanism of this regulation is not completely understood. In this paper we show that C-terminal truncation of NR2A and NR2C subunits in mice (NR2A/C(DeltaC/DeltaC)) impairs synaptic transmission and plasticity at the cerebellar mossy fiber-granule cell relay. Activation of synaptic NMDA receptors could be distinguished from that of extrasynaptic receptors by using the glutamate scavenger glutamate pyruvate transaminase and the open channel blocker MK801. NR2A/C(DeltaC/DeltaC) mice exhibited a specific reduction in synaptic NMDA receptor activation attributable to a severalfold decrease in channel open probability but not channel conductance. Immunodetection revealed normal developmental expression of NR subunit proteins. Quantitative immunogold analyses with an antibody to NR1 indicated that the reduction in receptor activation is not attributed to a reduced number of NR1-containing receptors in postsynaptic densities. Thus, NR2A/NR2C subunits and particularly their C termini regulate synaptic NMDA receptor activation and function by enhancing channel open probability, which is critical for long-term potentiation induction.
Rossi
Paola
P
Department of Molecular and Cellular Physiology and Istituto Nazionale per la Fisica della Materia, University of Pavia, I 27100 Pavia, Italy.
Sola
Elisabetta
E
Taglietti
Vanni
V
Borchardt
Thilo
T
Steigerwald
Frank
F
Utvik
Jo Kristian
JK
Ottersen
Ole Petter
OP
Köhr
Georg
G
D'Angelo
Egidio
E
D000375:Aging / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D015151:Immunoblotting; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D018377:Neurotransmitter Agents / Q000378:metabolism; D018408:Patch-Clamp Techniques; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; C120997:NR2A NMDA receptor; C432823:NR2C NMDA receptor; D018377:Neurotransmitter Agents; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; D000410:Alanine Transaminase