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Metabotropic glutamate receptor 1 (mGluR1) and 5 (mGluR5) regulate late phases of LTP and LTD in the hippocampal CA1 region in vitro.

Neyman S, Manahan-Vaughan D - Eur. J. Neurosci. (2008)

Bottom Line: In addition, although effects in vivo are consistently described, conflicting reports of the involvement of mGluRs in hippocampal synaptic plasticity in vitro exist.Application after either HFT or LFS had no effect.Application after LFS significantly impaired late phases of LTD.

View Article: PubMed Central - PubMed

Affiliation: Institute for Physiology of the Charité, Synaptic Plasticity Research Group, Humboldt University, Berlin, Germany.

ABSTRACT
The group I metabotropic glutamate receptors, mGluR1 and mGluR5, exhibit differences in their regulation of synaptic plasticity, suggesting that these receptors may subserve separate functional roles in information storage. In addition, although effects in vivo are consistently described, conflicting reports of the involvement of mGluRs in hippocampal synaptic plasticity in vitro exist. We therefore addressed the involvement of mGluR1 and mGluR5 in long-term potentiation (LTP) and long-term depression (LTD) in the hippocampal CA1 region of adult male rats in vitro. The mGluR1 antagonist (S)-(+)-alpha-amino-4-carboxy-2-methylbenzene-acetic acid (LY367385) impaired both induction and late phases of both LTP and LTD, when applied before high-frequency tetanization (HFT; 100 Hz) or low-frequency stimulation (LFS; 1 Hz), respectively. Application after either HFT or LFS had no effect. The mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP), when given before HFT, inhibited both the induction and late phases of LTP. When given after HFT, late LTP was inhibited. MPEP, given prior to LFS, impaired LTD induction, although stable LTD was still expressed. Application after LFS significantly impaired late phases of LTD. Activation of protein synthesis may comprise a key mechanism underlying the group I mGluR contribution to synaptic plasticity. The mGluR5 agonist (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG) converted short-term depression into LTD. Effects were prevented by application of the protein synthesis inhibitor anisomycin, suggesting that protein synthesis is triggered by group I mGluR activation to enable persistency of synaptic plasticity. Taken together, these data support the notion that both mGluR1 and mGluR5 are critically involved in bidirectional synaptic plasticity in the CA1 region and may enable functional differences in information encoding through LTP and LTD.

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Application of an mGluR1 antagonist prior to, but not after, HFT prevented LTP in the CA1 region. (A) HFT (100 Hz) induced persistent LTP (which lasted for at least 4 h) in the CA1 region in vitro. Application of the mGluR1 antagonist LY367285 (100 µm), for 20 min prior to HFT, significantly prevented the induction and expression of LTD. Application of LY367285 (100 µm) for 20 min immediately after HFT had no effect. Bar indicates drug application before (black) or after (grey) HFT. (B) Application of LY367285 (100 µm) did not affect basal synaptic transmission compared to controls. Bar indicates drug application. Insets: evoked potentials obtained in the presence of vehicle or LY387385 (applied pre-HFT), at the timepoints noted: vertical bars, 2 mV; horizontal bars, 2 ms.
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fig01: Application of an mGluR1 antagonist prior to, but not after, HFT prevented LTP in the CA1 region. (A) HFT (100 Hz) induced persistent LTP (which lasted for at least 4 h) in the CA1 region in vitro. Application of the mGluR1 antagonist LY367285 (100 µm), for 20 min prior to HFT, significantly prevented the induction and expression of LTD. Application of LY367285 (100 µm) for 20 min immediately after HFT had no effect. Bar indicates drug application before (black) or after (grey) HFT. (B) Application of LY367285 (100 µm) did not affect basal synaptic transmission compared to controls. Bar indicates drug application. Insets: evoked potentials obtained in the presence of vehicle or LY387385 (applied pre-HFT), at the timepoints noted: vertical bars, 2 mV; horizontal bars, 2 ms.

Mentions: Application of LY367385 (100 µm) for 20 min immediately prior to HFT resulted in a significant inhibition of LTP in hippocampal slices (n = 5) compared to controls (n = 8; Fig. 1A; anova: within factor F1,23 = 36.466, P = 0.0001; between factor F1,23 = 8.214, P = 0.0001). A significant effect on the induction phase was evident (P < 0.05). In addition, the expression phase of LTP (late LTP, > 2 h) was markedly impaired compared to controls (Fig. 1A). LTP in control animals persisted for at least 4 h.


Metabotropic glutamate receptor 1 (mGluR1) and 5 (mGluR5) regulate late phases of LTP and LTD in the hippocampal CA1 region in vitro.

Neyman S, Manahan-Vaughan D - Eur. J. Neurosci. (2008)

Application of an mGluR1 antagonist prior to, but not after, HFT prevented LTP in the CA1 region. (A) HFT (100 Hz) induced persistent LTP (which lasted for at least 4 h) in the CA1 region in vitro. Application of the mGluR1 antagonist LY367285 (100 µm), for 20 min prior to HFT, significantly prevented the induction and expression of LTD. Application of LY367285 (100 µm) for 20 min immediately after HFT had no effect. Bar indicates drug application before (black) or after (grey) HFT. (B) Application of LY367285 (100 µm) did not affect basal synaptic transmission compared to controls. Bar indicates drug application. Insets: evoked potentials obtained in the presence of vehicle or LY387385 (applied pre-HFT), at the timepoints noted: vertical bars, 2 mV; horizontal bars, 2 ms.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2327219&req=5

fig01: Application of an mGluR1 antagonist prior to, but not after, HFT prevented LTP in the CA1 region. (A) HFT (100 Hz) induced persistent LTP (which lasted for at least 4 h) in the CA1 region in vitro. Application of the mGluR1 antagonist LY367285 (100 µm), for 20 min prior to HFT, significantly prevented the induction and expression of LTD. Application of LY367285 (100 µm) for 20 min immediately after HFT had no effect. Bar indicates drug application before (black) or after (grey) HFT. (B) Application of LY367285 (100 µm) did not affect basal synaptic transmission compared to controls. Bar indicates drug application. Insets: evoked potentials obtained in the presence of vehicle or LY387385 (applied pre-HFT), at the timepoints noted: vertical bars, 2 mV; horizontal bars, 2 ms.
Mentions: Application of LY367385 (100 µm) for 20 min immediately prior to HFT resulted in a significant inhibition of LTP in hippocampal slices (n = 5) compared to controls (n = 8; Fig. 1A; anova: within factor F1,23 = 36.466, P = 0.0001; between factor F1,23 = 8.214, P = 0.0001). A significant effect on the induction phase was evident (P < 0.05). In addition, the expression phase of LTP (late LTP, > 2 h) was markedly impaired compared to controls (Fig. 1A). LTP in control animals persisted for at least 4 h.

Bottom Line: In addition, although effects in vivo are consistently described, conflicting reports of the involvement of mGluRs in hippocampal synaptic plasticity in vitro exist.Application after either HFT or LFS had no effect.Application after LFS significantly impaired late phases of LTD.

View Article: PubMed Central - PubMed

Affiliation: Institute for Physiology of the Charité, Synaptic Plasticity Research Group, Humboldt University, Berlin, Germany.

ABSTRACT
The group I metabotropic glutamate receptors, mGluR1 and mGluR5, exhibit differences in their regulation of synaptic plasticity, suggesting that these receptors may subserve separate functional roles in information storage. In addition, although effects in vivo are consistently described, conflicting reports of the involvement of mGluRs in hippocampal synaptic plasticity in vitro exist. We therefore addressed the involvement of mGluR1 and mGluR5 in long-term potentiation (LTP) and long-term depression (LTD) in the hippocampal CA1 region of adult male rats in vitro. The mGluR1 antagonist (S)-(+)-alpha-amino-4-carboxy-2-methylbenzene-acetic acid (LY367385) impaired both induction and late phases of both LTP and LTD, when applied before high-frequency tetanization (HFT; 100 Hz) or low-frequency stimulation (LFS; 1 Hz), respectively. Application after either HFT or LFS had no effect. The mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP), when given before HFT, inhibited both the induction and late phases of LTP. When given after HFT, late LTP was inhibited. MPEP, given prior to LFS, impaired LTD induction, although stable LTD was still expressed. Application after LFS significantly impaired late phases of LTD. Activation of protein synthesis may comprise a key mechanism underlying the group I mGluR contribution to synaptic plasticity. The mGluR5 agonist (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG) converted short-term depression into LTD. Effects were prevented by application of the protein synthesis inhibitor anisomycin, suggesting that protein synthesis is triggered by group I mGluR activation to enable persistency of synaptic plasticity. Taken together, these data support the notion that both mGluR1 and mGluR5 are critically involved in bidirectional synaptic plasticity in the CA1 region and may enable functional differences in information encoding through LTP and LTD.

Show MeSH
Related in: MedlinePlus