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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.

Zhang XH, Wu LJ, Gong B, Ren M, Li BM, Zhuo M - Mol Brain (2008)

Bottom Line: Studies using genetic and pharmacological approaches have reported inconsistent results of the requirement of NR2B-containing NMDARs in LTP in the CA1 region.Inhibition of NR2B-NMDARs did not affect the late phase LTP induced by four-train HFS.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institutes of Brain Science, Fudan University, Shanghai, PR China. xuehan.zhang@utoronto.ca

ABSTRACT
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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NR2B-NMDARs are not required for L-LTP induced by HFS protocol in area CA1. A. Schematic diagram of the high frequency stimulation (HFS; 4 trains). B. Late phase LTP of field EPSP induced by the HFS in control (n = 7 slices) and in the presence of Ro25-6981 (n = 5 slices). Ro25-7981 had no effect on the L-LTP.
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Figure 4: NR2B-NMDARs are not required for L-LTP induced by HFS protocol in area CA1. A. Schematic diagram of the high frequency stimulation (HFS; 4 trains). B. Late phase LTP of field EPSP induced by the HFS in control (n = 7 slices) and in the presence of Ro25-6981 (n = 5 slices). Ro25-7981 had no effect on the L-LTP.

Mentions: To address the possible role of NR2B-NMDARs in L-LTP, we used a four-train HFS to induce L-LTP in the CA1 region (Figure 4A). As shown in Figure 5B, the potentiation of filed EPSP was robust and sustained for over 3 h after the delivery of the HFS (209.6 ± 57.0% of baseline at 170–180 min post-HFS p < 0.05 vs. baseline, n = 7 slices). Bath application of 0.5 μM Ro25-6981 did not affect the L-LTP (Figure 4B: 200.7 ± 33.5% of baseline; p < 0.05 vs. baseline; p > 0.05 vs. control, n = 5 slices). This result indicates that NR2B-NMDARs are not required for the L-LTP.


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.

Zhang XH, Wu LJ, Gong B, Ren M, Li BM, Zhuo M - Mol Brain (2008)

NR2B-NMDARs are not required for L-LTP induced by HFS protocol in area CA1. A. Schematic diagram of the high frequency stimulation (HFS; 4 trains). B. Late phase LTP of field EPSP induced by the HFS in control (n = 7 slices) and in the presence of Ro25-6981 (n = 5 slices). Ro25-7981 had no effect on the L-LTP.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2570668&req=5

Figure 4: NR2B-NMDARs are not required for L-LTP induced by HFS protocol in area CA1. A. Schematic diagram of the high frequency stimulation (HFS; 4 trains). B. Late phase LTP of field EPSP induced by the HFS in control (n = 7 slices) and in the presence of Ro25-6981 (n = 5 slices). Ro25-7981 had no effect on the L-LTP.
Mentions: To address the possible role of NR2B-NMDARs in L-LTP, we used a four-train HFS to induce L-LTP in the CA1 region (Figure 4A). As shown in Figure 5B, the potentiation of filed EPSP was robust and sustained for over 3 h after the delivery of the HFS (209.6 ± 57.0% of baseline at 170–180 min post-HFS p < 0.05 vs. baseline, n = 7 slices). Bath application of 0.5 μM Ro25-6981 did not affect the L-LTP (Figure 4B: 200.7 ± 33.5% of baseline; p < 0.05 vs. baseline; p > 0.05 vs. control, n = 5 slices). This result indicates that NR2B-NMDARs are not required for the L-LTP.

Bottom Line: Studies using genetic and pharmacological approaches have reported inconsistent results of the requirement of NR2B-containing NMDARs in LTP in the CA1 region.Inhibition of NR2B-NMDARs did not affect the late phase LTP induced by four-train HFS.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institutes of Brain Science, Fudan University, Shanghai, PR China. xuehan.zhang@utoronto.ca

ABSTRACT
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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