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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 LTP induced by pairing protocol in area CA1. A. Schematic diagram of the pairing protocol. B. Pairing protocol, as indicated by the arrow, induced a significant LTP in CA1 pyramidal neurons (n = 6). Sample traces of EPSC are the averages of 7 consecutive responses recorded during 5–10 min and 25–30 min, respectively. C. Bath application of Ro25-6981 (0.5 μM) had no effect on the LTP (n = 5). D. Histogram showing the effect of Ro25-6981 on the LTP. p > 0.05 vs. control.
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Figure 2: NR2B-NMDARs are not required for LTP induced by pairing protocol in area CA1. A. Schematic diagram of the pairing protocol. B. Pairing protocol, as indicated by the arrow, induced a significant LTP in CA1 pyramidal neurons (n = 6). Sample traces of EPSC are the averages of 7 consecutive responses recorded during 5–10 min and 25–30 min, respectively. C. Bath application of Ro25-6981 (0.5 μM) had no effect on the LTP (n = 5). D. Histogram showing the effect of Ro25-6981 on the LTP. p > 0.05 vs. control.

Mentions: Next, we examined the effect of NR2B inhibition on LTP induced by pairing protocol (Figure 2A). Whole-cell recordings were done in CA1 pyramidal cells. The pairing protocol induced a significant potentiation of synaptic responses (Figure 2B: 192.1 ± 22.0% of baseline, n = 6 slices; p < 0.05 vs. baseline). Bath application of 0.5 μM Ro25-6981 did not affect the synaptic potentiation (Figure 2C: 181.6 ± 22.8% of baseline, n = 5 slices; p < 0.05 vs. baseline). As shown in Figure 2D, there was no significant difference in LTP amplitudes in the presence and absence of Ro25-6981 (25–30 min post-induction, p > 0.05 for Ro25-6981 vs. control). This result indicates that NR2B-NMDARs are not required for LTP induced by the pairing protocol in the CA1 region, consistent with the previous report by Liu et al. [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.

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

NR2B-NMDARs are not required for LTP induced by pairing protocol in area CA1. A. Schematic diagram of the pairing protocol. B. Pairing protocol, as indicated by the arrow, induced a significant LTP in CA1 pyramidal neurons (n = 6). Sample traces of EPSC are the averages of 7 consecutive responses recorded during 5–10 min and 25–30 min, respectively. C. Bath application of Ro25-6981 (0.5 μM) had no effect on the LTP (n = 5). D. Histogram showing the effect of Ro25-6981 on the LTP. p > 0.05 vs. control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: NR2B-NMDARs are not required for LTP induced by pairing protocol in area CA1. A. Schematic diagram of the pairing protocol. B. Pairing protocol, as indicated by the arrow, induced a significant LTP in CA1 pyramidal neurons (n = 6). Sample traces of EPSC are the averages of 7 consecutive responses recorded during 5–10 min and 25–30 min, respectively. C. Bath application of Ro25-6981 (0.5 μM) had no effect on the LTP (n = 5). D. Histogram showing the effect of Ro25-6981 on the LTP. p > 0.05 vs. control.
Mentions: Next, we examined the effect of NR2B inhibition on LTP induced by pairing protocol (Figure 2A). Whole-cell recordings were done in CA1 pyramidal cells. The pairing protocol induced a significant potentiation of synaptic responses (Figure 2B: 192.1 ± 22.0% of baseline, n = 6 slices; p < 0.05 vs. baseline). Bath application of 0.5 μM Ro25-6981 did not affect the synaptic potentiation (Figure 2C: 181.6 ± 22.8% of baseline, n = 5 slices; p < 0.05 vs. baseline). As shown in Figure 2D, there was no significant difference in LTP amplitudes in the presence and absence of Ro25-6981 (25–30 min post-induction, p > 0.05 for Ro25-6981 vs. control). This result indicates that NR2B-NMDARs are not required for LTP induced by the pairing protocol in the CA1 region, consistent with the previous report by Liu et al. [9]

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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