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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 mGluR5 antagonist either prior to or 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 mGluR5 antagonist MPEP (40 µm), for 20 min prior to HFT, significantly prevented both the induction and the expression of LTP. Application of MPEP (40 µm) for 20 min after HFT significantly prevented the expression of LTP beyond 2 h post-HFT. Bar indicates drug application before (black) or after (grey) HFT. (B) Application of MPEP (40 µm) did not affect basal synaptic transmission compared to controls. Bar indicates drug application. Insets: evoked potentials obtained in the presence of vehicle or MPEP (applied pre-HFT) at the timepoints noted: vertical bars, 2 mV; horizontal bars, 2 ms.
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fig02: Application of an mGluR5 antagonist either prior to or 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 mGluR5 antagonist MPEP (40 µm), for 20 min prior to HFT, significantly prevented both the induction and the expression of LTP. Application of MPEP (40 µm) for 20 min after HFT significantly prevented the expression of LTP beyond 2 h post-HFT. Bar indicates drug application before (black) or after (grey) HFT. (B) Application of MPEP (40 µm) did not affect basal synaptic transmission compared to controls. Bar indicates drug application. Insets: evoked potentials obtained in the presence of vehicle or MPEP (applied pre-HFT) at the timepoints noted: vertical bars, 2 mV; horizontal bars, 2 ms.

Mentions: Application of 40 µm MPEP (n = 9) for 20 min prior to HFT resulted in a significant impairment of both induction and expression of LTP (Fig. 2A; anova: within factor F1,19 = 10.367, P = 0.0001; between factor F1,19 = 1.806, P = 0.0373). Taking into account that activation of mGluR5 can modulate NMDAR-mediated currents (Mannaioni et al., 2001), we examined whether the same concentration of MPEP would affect LTP when applied after HFT. Here, we found that MPEP in a concentration of 40 µm (n = 8) also caused a significant impairment of LTP (Fig. 2A) in comparison to controls (anova: within factor F1,23 = 38.994, P = 0.0001; between factor F1,23 = 4.536, P = 0.0001). This effect did not derive from effects on basal synaptic transmission, which remained stable over the 4-h monitoring period and did not differ after MPEP treatment (40 µm, n = 9) when compared with control slices (n = 12; Fig. 2B). These data suggest that mGluR5 contributes to processes that underlie both the induction and late phases of LTP.


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 mGluR5 antagonist either prior to or 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 mGluR5 antagonist MPEP (40 µm), for 20 min prior to HFT, significantly prevented both the induction and the expression of LTP. Application of MPEP (40 µm) for 20 min after HFT significantly prevented the expression of LTP beyond 2 h post-HFT. Bar indicates drug application before (black) or after (grey) HFT. (B) Application of MPEP (40 µm) did not affect basal synaptic transmission compared to controls. Bar indicates drug application. Insets: evoked potentials obtained in the presence of vehicle or MPEP (applied pre-HFT) at the timepoints noted: vertical bars, 2 mV; horizontal bars, 2 ms.
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Related In: Results  -  Collection

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

fig02: Application of an mGluR5 antagonist either prior to or 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 mGluR5 antagonist MPEP (40 µm), for 20 min prior to HFT, significantly prevented both the induction and the expression of LTP. Application of MPEP (40 µm) for 20 min after HFT significantly prevented the expression of LTP beyond 2 h post-HFT. Bar indicates drug application before (black) or after (grey) HFT. (B) Application of MPEP (40 µm) did not affect basal synaptic transmission compared to controls. Bar indicates drug application. Insets: evoked potentials obtained in the presence of vehicle or MPEP (applied pre-HFT) at the timepoints noted: vertical bars, 2 mV; horizontal bars, 2 ms.
Mentions: Application of 40 µm MPEP (n = 9) for 20 min prior to HFT resulted in a significant impairment of both induction and expression of LTP (Fig. 2A; anova: within factor F1,19 = 10.367, P = 0.0001; between factor F1,19 = 1.806, P = 0.0373). Taking into account that activation of mGluR5 can modulate NMDAR-mediated currents (Mannaioni et al., 2001), we examined whether the same concentration of MPEP would affect LTP when applied after HFT. Here, we found that MPEP in a concentration of 40 µm (n = 8) also caused a significant impairment of LTP (Fig. 2A) in comparison to controls (anova: within factor F1,23 = 38.994, P = 0.0001; between factor F1,23 = 4.536, P = 0.0001). This effect did not derive from effects on basal synaptic transmission, which remained stable over the 4-h monitoring period and did not differ after MPEP treatment (40 µm, n = 9) when compared with control slices (n = 12; Fig. 2B). These data suggest that mGluR5 contributes to processes that underlie both the induction and late phases of LTP.

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