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Long-term potentiation in the CA1 hippocampus induced by NR2A subunit-containing NMDA glutamate receptors is mediated by Ras-GRF2/Erk map kinase signaling.

Jin SX, Feig LA - PLoS ONE (2010)

Bottom Line: These receptors consist of calcium-permeating NR1 and multiple regulatory NR2 subunits.A majority of studies show that both NR2A and NR2B-containing NMDARs can contribute to LTP, but their unique contributions to this form of synaptic plasticity remain poorly understood.This difference add new significance to the observation that the relative levels of these NMDAR subtypes is regulated in neurons, such that NR2A-containing receptors become more prominent late in postnatal development, after sensory experience and synaptic activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts, United States of America.

ABSTRACT

Background: NMDA-type glutamate receptors (NMDARs) are major contributors to long-term potentiation (LTP), a form of synaptic plasticity implicated in the process of learning and memory. These receptors consist of calcium-permeating NR1 and multiple regulatory NR2 subunits. A majority of studies show that both NR2A and NR2B-containing NMDARs can contribute to LTP, but their unique contributions to this form of synaptic plasticity remain poorly understood.

Methodology/principal findings: In this study, we show that NR2A and NR2B-containing receptors promote LTP differently in the CA1 hippocampus of 1-month old mice, with the NR2A receptors functioning through Ras-GRF2 and its downstream effector, Erk Map kinase, and NR2B receptors functioning independently of these signaling molecules.

Conclusions/significance: This study demonstrates that NR2A-, but not NR2B, containing NMDA receptors induce LTP in pyramidal neurons of the CA1 hippocampus from 1 month old mice through Ras-GRF2 and Erk. This difference add new significance to the observation that the relative levels of these NMDAR subtypes is regulated in neurons, such that NR2A-containing receptors become more prominent late in postnatal development, after sensory experience and synaptic activity.

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LFS paring-induced LTP in double Ras-GRF1/2 knock-out mice.LFS paring-induced LTP was measured in hippocampal brain slices from double Ras-GRF1/Ras-GRF2 knockout mice in normal (black filled circles; n = 5) and in the presence of 50 ηM NVP (green filled triangles; n = 6) or 0.5 µM Ro (red filled squares; n = 8) ACSF. Inset: Averaged EPSCs before and after LFS paring in control (left) and in the presence of NVP (middle) or Ro (right) ACSF. Calibration: horizontal, 50 ms; vertical, 50 pA.
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pone-0011732-g004: LFS paring-induced LTP in double Ras-GRF1/2 knock-out mice.LFS paring-induced LTP was measured in hippocampal brain slices from double Ras-GRF1/Ras-GRF2 knockout mice in normal (black filled circles; n = 5) and in the presence of 50 ηM NVP (green filled triangles; n = 6) or 0.5 µM Ro (red filled squares; n = 8) ACSF. Inset: Averaged EPSCs before and after LFS paring in control (left) and in the presence of NVP (middle) or Ro (right) ACSF. Calibration: horizontal, 50 ms; vertical, 50 pA.

Mentions: We showed previously that GRF1, which is known associate with NR2B receptors, mediates LTD but not TBS-induced LTP as measured by field recordings in the CA1 hippocampus of 1-month old mice [9]. Fig. 4 shows that when LTP was induced by the LFS-pairing protocol in single cells of brain slices from double GRF1/GRF2 knockout mice, where NR2A/GRF2/LTP signaling is blocked, normal LTP was still observed. In contrast, pre-incubation with the NR2B inhibitor led to the loss of LTP induction, while pre-incubation with the NR2A inhibitor had no effect. These results confirms that although GRF1 associates with NR2B receptors, NR2B-induced LTP functions through neither Ras-GRF1 nor Ras-GRF2.


Long-term potentiation in the CA1 hippocampus induced by NR2A subunit-containing NMDA glutamate receptors is mediated by Ras-GRF2/Erk map kinase signaling.

Jin SX, Feig LA - PLoS ONE (2010)

LFS paring-induced LTP in double Ras-GRF1/2 knock-out mice.LFS paring-induced LTP was measured in hippocampal brain slices from double Ras-GRF1/Ras-GRF2 knockout mice in normal (black filled circles; n = 5) and in the presence of 50 ηM NVP (green filled triangles; n = 6) or 0.5 µM Ro (red filled squares; n = 8) ACSF. Inset: Averaged EPSCs before and after LFS paring in control (left) and in the presence of NVP (middle) or Ro (right) ACSF. Calibration: horizontal, 50 ms; vertical, 50 pA.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2908693&req=5

pone-0011732-g004: LFS paring-induced LTP in double Ras-GRF1/2 knock-out mice.LFS paring-induced LTP was measured in hippocampal brain slices from double Ras-GRF1/Ras-GRF2 knockout mice in normal (black filled circles; n = 5) and in the presence of 50 ηM NVP (green filled triangles; n = 6) or 0.5 µM Ro (red filled squares; n = 8) ACSF. Inset: Averaged EPSCs before and after LFS paring in control (left) and in the presence of NVP (middle) or Ro (right) ACSF. Calibration: horizontal, 50 ms; vertical, 50 pA.
Mentions: We showed previously that GRF1, which is known associate with NR2B receptors, mediates LTD but not TBS-induced LTP as measured by field recordings in the CA1 hippocampus of 1-month old mice [9]. Fig. 4 shows that when LTP was induced by the LFS-pairing protocol in single cells of brain slices from double GRF1/GRF2 knockout mice, where NR2A/GRF2/LTP signaling is blocked, normal LTP was still observed. In contrast, pre-incubation with the NR2B inhibitor led to the loss of LTP induction, while pre-incubation with the NR2A inhibitor had no effect. These results confirms that although GRF1 associates with NR2B receptors, NR2B-induced LTP functions through neither Ras-GRF1 nor Ras-GRF2.

Bottom Line: These receptors consist of calcium-permeating NR1 and multiple regulatory NR2 subunits.A majority of studies show that both NR2A and NR2B-containing NMDARs can contribute to LTP, but their unique contributions to this form of synaptic plasticity remain poorly understood.This difference add new significance to the observation that the relative levels of these NMDAR subtypes is regulated in neurons, such that NR2A-containing receptors become more prominent late in postnatal development, after sensory experience and synaptic activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts, United States of America.

ABSTRACT

Background: NMDA-type glutamate receptors (NMDARs) are major contributors to long-term potentiation (LTP), a form of synaptic plasticity implicated in the process of learning and memory. These receptors consist of calcium-permeating NR1 and multiple regulatory NR2 subunits. A majority of studies show that both NR2A and NR2B-containing NMDARs can contribute to LTP, but their unique contributions to this form of synaptic plasticity remain poorly understood.

Methodology/principal findings: In this study, we show that NR2A and NR2B-containing receptors promote LTP differently in the CA1 hippocampus of 1-month old mice, with the NR2A receptors functioning through Ras-GRF2 and its downstream effector, Erk Map kinase, and NR2B receptors functioning independently of these signaling molecules.

Conclusions/significance: This study demonstrates that NR2A-, but not NR2B, containing NMDA receptors induce LTP in pyramidal neurons of the CA1 hippocampus from 1 month old mice through Ras-GRF2 and Erk. This difference add new significance to the observation that the relative levels of these NMDAR subtypes is regulated in neurons, such that NR2A-containing receptors become more prominent late in postnatal development, after sensory experience and synaptic activity.

Show MeSH