Limits...
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.

Show MeSH
The effects of MEK and PI3-kinase inhibitors on LFS induced LTP in WT mice.A LTP was measured in cells in which SL327 (100 µM) was present in recording electrode solution (black filled circles; 0.2% DMSO; n = 7). Tissues were bathed in either 0.5 µM Ro (red filled squares; n = 5) or 50 ηM NVP (green filled triangles; n = 7). B LTP was measured in cells in which LY294002 (Ly) (100 µM) was included in the recording electrode solution (black filled circles; n = 5). These tissues were also bathed in either 0.5µM Ro (red filled squares; n = 5) or 50 ηM NVP (green filled triangles; n = 7). C. Summary graph showing the effects of these drugs on the LTP.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2908693&req=5

pone-0011732-g005: The effects of MEK and PI3-kinase inhibitors on LFS induced LTP in WT mice.A LTP was measured in cells in which SL327 (100 µM) was present in recording electrode solution (black filled circles; 0.2% DMSO; n = 7). Tissues were bathed in either 0.5 µM Ro (red filled squares; n = 5) or 50 ηM NVP (green filled triangles; n = 7). B LTP was measured in cells in which LY294002 (Ly) (100 µM) was included in the recording electrode solution (black filled circles; n = 5). These tissues were also bathed in either 0.5µM Ro (red filled squares; n = 5) or 50 ηM NVP (green filled triangles; n = 7). C. Summary graph showing the effects of these drugs on the LTP.

Mentions: We then used a similar strategy to investigate whether a known downstream effector of Ras-GRF2, Erk Map kinase, also plays a sub-type specific role in NMDA receptor signaling. In particular, we tested the effect of including in the recording electrode, SL327, an inhibitor of Mek kinase, the upstream activator of Erk Map kinase. Fig 5A shows that SL327 treated neurons display normal LTP (Fig 5A; black diamond and 5C), implying that either Erk activation is not important for LFS-induced LTP, or that it selectively contributes to either NR2A or NR2B receptor signaling but not both. To distinguish between these possibilities, we included in the bath solution either an NR2A or NR2B inhibitor. We found that SL327 suppressed LTP induction when NR2B, but not NR2A receptors were blocked. Thus, like Ras-GRF2, Erk activity is needed for NR2A, but not NR2B, -induced LTP in CA1 pyramidal neurons of the hippocampus from 1-month old mice.


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)

The effects of MEK and PI3-kinase inhibitors on LFS induced LTP in WT mice.A LTP was measured in cells in which SL327 (100 µM) was present in recording electrode solution (black filled circles; 0.2% DMSO; n = 7). Tissues were bathed in either 0.5 µM Ro (red filled squares; n = 5) or 50 ηM NVP (green filled triangles; n = 7). B LTP was measured in cells in which LY294002 (Ly) (100 µM) was included in the recording electrode solution (black filled circles; n = 5). These tissues were also bathed in either 0.5µM Ro (red filled squares; n = 5) or 50 ηM NVP (green filled triangles; n = 7). C. Summary graph showing the effects of these drugs on the LTP.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0011732-g005: The effects of MEK and PI3-kinase inhibitors on LFS induced LTP in WT mice.A LTP was measured in cells in which SL327 (100 µM) was present in recording electrode solution (black filled circles; 0.2% DMSO; n = 7). Tissues were bathed in either 0.5 µM Ro (red filled squares; n = 5) or 50 ηM NVP (green filled triangles; n = 7). B LTP was measured in cells in which LY294002 (Ly) (100 µM) was included in the recording electrode solution (black filled circles; n = 5). These tissues were also bathed in either 0.5µM Ro (red filled squares; n = 5) or 50 ηM NVP (green filled triangles; n = 7). C. Summary graph showing the effects of these drugs on the LTP.
Mentions: We then used a similar strategy to investigate whether a known downstream effector of Ras-GRF2, Erk Map kinase, also plays a sub-type specific role in NMDA receptor signaling. In particular, we tested the effect of including in the recording electrode, SL327, an inhibitor of Mek kinase, the upstream activator of Erk Map kinase. Fig 5A shows that SL327 treated neurons display normal LTP (Fig 5A; black diamond and 5C), implying that either Erk activation is not important for LFS-induced LTP, or that it selectively contributes to either NR2A or NR2B receptor signaling but not both. To distinguish between these possibilities, we included in the bath solution either an NR2A or NR2B inhibitor. We found that SL327 suppressed LTP induction when NR2B, but not NR2A receptors were blocked. Thus, like Ras-GRF2, Erk activity is needed for NR2A, but not NR2B, -induced LTP in CA1 pyramidal neurons of the hippocampus from 1-month old mice.

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