Activation of NR2B-containing NMDA receptors is not required for NMDA receptor-dependent long-term depression.
The triggering of both NMDA receptor-dependent long-term potentiation (LTP) and long-term depression (LTD) in the CA1 region of the hippocampus requires a rise in postsynaptic calcium. A prominent hypothesis has been that the detailed properties of this postsynaptic calcium signal dictate whether LTP or LTD is generated by a given pattern of synaptic activity. Recently, however, evidence has been presented that the subunit composition of the NMDA receptor (NMDAR) determines whether a synapse undergoes LTP or LTD with NR2A-containing NMDARs triggering LTP and NR2B-containing NMDARs triggering LTD. In the present study, the role of NR2B-containing synaptic NMDARs in the induction of LTD in CA1 pyramidal cells has been studied using the selective NR2B antagonists, ifenprodil and Ro25-6981. While both antagonists reduced NMDAR-mediated synaptic currents, neither prevented induction of LTD. These results demonstrate that activation of NR2B-containing NMDARs is not an absolute requirement for the induction of LTD in the hippocampus.
Morishita
Wade
W
Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA 94304-5485, USA.
Lu
Wei
W
Smith
Gordon B
GB
Nicoll
Roger A
RA
Bear
Mark F
MF
Malenka
Robert C
RC
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D016202:N-Methylaspartate / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D010636:Phenols / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism / Q000502:physiology*
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; D010636:Phenols; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981; D016202:N-Methylaspartate; C010739:ifenprodil; D002118:Calcium