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Mol Brain. 2008 Sep 30;1:9. doi: 10.1186/1756-6606-1-9.

Induction- and conditioning-protocol dependent involvement of NR2B-containing NMDA receptors in synaptic potentiation and contextual fear memory in the hippocampal CA1 region of rats.

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Institutes of Brain Science, Fudan University, Shanghai, PR China.


Long-term potentiation (LTP) in the hippocampal CA1 region requires the activation of N-methyl-D-aspartate receptors (NMDARs). Studies using genetic and pharmacological approaches have reported inconsistent results of the requirement of NR2B-containing NMDARs in LTP in the CA1 region. Pharmacological studies showed that NR2B-containing NMDARs are not required for LTP, while genetic studies reported that over-expression of NR2B-NMDARs enhances LTP and hippocampus-dependent memory. Here, we provide evidence showing that the functional role of NR2B-NMDARs in hippocampal LTP and memory depends on LTP-inducing and behavior-conditioning protocols. Inhibition of NR2B-NMDARs with the NR2B selective antagonist ifenprodil or Ro25-6981 suppressed LTP induced by spike-timing protocol, with no impact on LTP induced by pairing protocol or two-train high-frequency stimulation (HFS) protocol. Inhibition of NR2B-NMDARs did not affect the late phase LTP induced by four-train HFS. Ca²(+) imaging showed that there was difference in kinetics of intracellular Ca²(+) signals induced by spiking-timing and pairing protocols. Pre-training intra-CA1 infusion of ifenprodil or Ro25-6981 impaired the contextual fear memory induced by five CS-US pairings, with no effect on the memory induced by one CS-US pairing.

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