NR2A-/- mice lack long-term potentiation but retain NMDA receptor and L-type Ca2+ channel-dependent long-term depression in the juvenile superior colliculus.
Whether the subunit composition of NMDA receptors (NMDARs) controls the direction of long-term plasticity is currently disputed. In the visual layers of NR2A-/- juvenile superior colliculus (SC), synapses lose miniature NMDAR currents, leaving NR2B-rich receptors in extrasynaptic regions. Compared with wild type (WT), evoked NMDAR currents in mutant neurons have slower rise and decay times and lower NMDAR/AMPAR current ratios. Moreover, NMDAR and L-type Ca2+ channel-dependent SC long-term potentiation (LTP) is absent in NR2A-/- cells, whereas both WT and mutant neurons show long-duration, low-frequency-induced, long-term depression (LLF-LTD) that is blocked by either AP-5, nimodipine, or Ro 25-6981 [R-(R,S)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidine propranol]. Thus, NMDAR currents or signaling localized at the postsynaptic density are essential to SC NMDAR-dependent LTP, whereas extrasynaptic or NR2B-rich NMDARs are necessary for LLF-LTD. However, synaptic NMDARs as well as the NR2A subunit are missing in NR2A-/- mice. Therefore, NR2 subunit-specific ligand binding/channel properties and/or separate signaling pathways interacting with NMDARs at synaptic versus extrasynaptic receptors could underlie these results.
Zhao
Jian-Ping
JP
The McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. jpzhao@mit.edu
Constantine-Paton
Martha
M
D000367:Age Factors; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013477:Superior Colliculi / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D018691:Excitatory Amino Acid Antagonists; C120997:NR2A NMDA receptor; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate