Distinct trafficking and expression mechanisms underlie LTP and LTD of NMDA receptor-mediated synaptic responses.
Although an increasing number of studies have demonstrated the plasticity of NMDA receptor-mediated synaptic transmission, little is known about the molecular mechanisms that underlie this neurologically important process. In a study of NMDAR-mediated synaptic responses in hippocampal Schaffer-CA1 synapses whose AMPA receptor (AMPAR) activity is totally blocked, we uncovered differences between the trafficking mechanisms that underlie the long-term potentiation (LTP) and long-term depression (LTD) that can be induced in these cells under these conditions. The LTP-producing protocol failed to induce a change in the amplitude of NMDAR-mediated postsynaptic currents (NMDAR EPSCs) in the first 5-10 min, but induced gradual enhancement of NMDAR EPSCs thereafter that soon reached a stable magnitude. This "slow" LTP of NMDAR EPSCs (LTP(NMDA)) was blocked by inhibiting exocytosis or actin polymerization in postsynaptic cells. By contrast, LTD of NMDAR EPSCs (LTD(NMDA)) was immediately inducible, and, although it was blocked by the actin stabilizer, it was unaffected by exocytosis or endocytosis inhibitors. Furthermore, concomitant changes in the decay time of NMDAR EPSCs suggested that differential switches in NR2 subunit composition accompanied LTP(NMDA) and LTD(NMDA), and these changes were blocked by the calcium buffer BAPTA or an mGluR antagonist. Our results suggest that LTP(NMDA) and LTD(NMDA) utilize different NMDAR trafficking pathways and express different ratios of NMDAR subunits on the postsynaptic surface.
Peng
Yi
Y
Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China.
Zhao
Jiang
J
Gu
Qin-Hua
QH
Chen
Rong-Qing
RQ
Xu
Zhuo
Z
Yan
Jing-Zhi
JZ
Wang
Shan-Hui
SH
Liu
Su-Yi
SY
Chen
Zheng
Z
Lu
Wei
W
D000704:Analysis of Variance; D000818:Animals; D001703:Biophysics; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation; D004705:Endocytosis / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005089:Exocytosis / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018408:Patch-Clamp Techniques / Q000379:methods; D010590:Phalloidine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013744:Tetanus Toxin / Q000494:pharmacology; D053778:Thiazolidines / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D013744:Tetanus Toxin; D053778:Thiazolidines; D010590:Phalloidine; C037068:latrunculin B; C010739:ifenprodil; D002118:Calcium