The Journal of Neuroscience, December 12, 2007, 27(50):13649-13654; doi:10.1523/JNEUROSCI.3153-07.2007
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Brief Communications
NR2A–/– Mice Lack Long-Term Potentiation But Retain NMDA Receptor and L-Type Ca2+ Channel-Dependent Long-Term Depression in the Juvenile Superior Colliculus
Jian-Ping Zhao and
Martha Constantine-Paton
The McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
Correspondence should be addressed to Jian-Ping Zhao, The Massachusetts Institute of Technology, 77 Massachusetts Avenue, Building 46-4165, Cambridge, MA 02139. Email: jpzhao{at}mit.edu
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)-
-(4-hydroxyphenyl)-β-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.
Key words: NR2A–/–; synaptic NMDAR; extrasynaptic NMDAR; LTP; LTD; L-type Ca2+ channel
Received April 17, 2007;
revised Oct. 22, 2007;
accepted Oct. 23, 2007.
Correspondence should be addressed to Jian-Ping Zhao, The Massachusetts Institute of Technology, 77 Massachusetts Avenue, Building 46-4165, Cambridge, MA 02139. Email: jpzhao{at}mit.edu