Role of NMDA receptor subtypes in governing the direction of hippocampal synaptic plasticity.
Activation of N-methyl-d-aspartate subtype glutamate receptors (NMDARs) is required for long-term potentiation (LTP) and long-term depression (LTD) of excitatory synaptic transmission at hippocampal CA1 synapses, the proposed cellular substrates of learning and memory. However, little is known about how activation of NMDARs leads to these two opposing forms of synaptic plasticity. Using hippocampal slice preparations, we showed that selectively blocking NMDARs that contain the NR2B subunit abolishes the induction of LTD but not LTP. In contrast, preferential inhibition of NR2A-containing NMDARs prevents the induction of LTP without affecting LTD production. These results demonstrate that distinct NMDAR subunits are critical factors that determine the polarity of synaptic plasticity.
Liu
Lidong
L
Brain Research Centre, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada.
Wong
Tak Pan
TP
Pozza
Mario F
MF
Lingenhoehl
Kurt
K
Wang
Yushan
Y
Sheng
Morgan
M
Auberson
Yves P
YP
Wang
Yu Tian
YT
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects; D036881:Long-Term Synaptic Depression / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010636:Phenols / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects
D018691:Excitatory Amino Acid Antagonists; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D010636:Phenols; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981; D015763:2-Amino-5-phosphonovalerate; C010739:ifenprodil; D002118:Calcium