Synaptic metaplasticity through NMDA receptor lateral diffusion.
Lateral diffusion of glutamate receptors was proposed as a mechanism for regulating receptor numbers at synapses and affecting synaptic functions, especially the efficiency of synaptic transmission. However, a direct link between receptor lateral diffusion and change in synaptic function has not yet been established. In the present study, we demonstrated NMDA receptor (NMDAR) lateral diffusion in CA1 neurons in hippocampal slices by detecting considerable recovery of spontaneous or evoked EPSCs from the block of (+)-MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate], an irreversible NMDAR open-channel blocker. We observed changes on both the number and the composition of synaptic NMDAR on recovery. More importantly, after the recovery, long-term potentiation (LTP)-producing protocol induced only LTD (long-term depression) instead of LTP. In contrast, a complete recovery from competitive NMDAR blocker D,L-AP-5 was observed without subsequent changes on synaptic plasticity. Our data suggest a revised model of NMDAR trafficking wherein extrasynaptic NMDARs, mostly NR1/NR2B receptors, move laterally into synaptic sites, resulting in altered rule of synaptic modification. Thus, CA1 synapses exhibit a novel form of metaplasticity in which the direction of synaptic modification can be reverted through subtype-specific lateral diffusion of NMDA receptors.
Zhao
Jiang
J
Department of Neurobiology, Key Laboratory of Neurodegenerative Disease of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
Peng
Yi
Y
Xu
Zhuo
Z
Chen
Rong-qing
RQ
Gu
Qin-hua
QH
Chen
Zheng
Z
Lu
Wei
W
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects
D018683:Excitatory Amino Acid Agents; D018756:GABA Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate