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Articles

Group 1 and 2 Metabotropic Glutamate Receptors Play Differential Roles in Hippocampal Long-Term Depression and Long-Term Potentiation in Freely Moving Rats

Denise Manahan-Vaughan
Journal of Neuroscience 1 May 1997, 17 (9) 3303-3311; DOI: https://doi.org/10.1523/JNEUROSCI.17-09-03303.1997
Denise Manahan-Vaughan
1Federal Institute for Neurobiology, Department of Neurophysiology, D-39008 Magdeburg, Germany
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    Fig. 1.

    LTD in the CA1 region in vivo is dependent on activation of both NMDA receptors and mGluRs.A, A low-frequency train (LFT) in the presence of a vehicle injection (n = 19) results in a robust LTD that persists for 24 hr. Previous injection of the NMDA receptor antagonist AP5 (20 mm/5 μl;n = 9) completely inhibits the induction of LTD, from t = 5 min post-LFT. B, Original analog traces showing evoked responses in the CA1 region at three time points: preinjection, t = 5 min, andt = 4 hr post-LFT, in (1) a vehicle-injected animal and (2) an animal injected with MCPG (200 mm/5 μl).C, MCPG (200 mm/5 μl;n = 8) significantly inhibits LTD, fromt = 120 min post-LFT, compared with vehicle-injected controls (n = 10). *p < 0.05, **p < 0.01, ***p < 0.001. Line breaks(//) indicate change in time scale.

  • Fig. 2.
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    Fig. 2.

    LTD in the CA1 region in vivo is modulated by group 1 mGluRs. A, The group 1 mGluR antagonist 4CPG (20 mm/5 μl; n = 7) partially impairs LTD when compared with vehicle-injected controls (n = 12), from t = 120 min post-LFT. This effect was significantly different from baseline values.B, Original analog traces showing evoked responses in the CA1 region at three time points: preinjection,t = 5 min, and t = 4 hr post-LFT, in an animal injected with 4CPG (20 mm/5 μl).C, Dose–response curve for the antagonist effect of 4CPG (2–40 mm/5 μl) on LTD in the CA1 region. The values represent the magnitude of LTD observed at 4 hr post-LFT.D, Application of 4CPG (20 mm/5 μl;n = 5) 5 min after LFT results in a significant inhibition of LTD, from t = 135 min post-HFT compared with vehicle-injected controls (n = 5). *p < 0.05. Line breaks(//) indicate change in time scale.

  • Fig. 3.
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    Fig. 3.

    LTP in the CA1 region in vivo is modulated by group 1 mGluRs. A, 4CPG (20 mm/5 μl; n = 5) significantly inhibits LTP, from t = 60 min after a high-frequency tetanus (HFT) compared with vehicle-injected controls (n = 6).B, Application of 4CPG (20 mm/5 μl;n = 5) 5 min after HFT results in a significant inhibition of LTP, from t = 45 min post-HFT compared with vehicle-injected controls (n = 5). *p < 0.05, **p < 0.01, ***p < 0.001. Line breaks(//) indicate change in time scale.

  • Fig. 4.
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    Fig. 4.

    LTD in the CA1 region in vivocritically involves group 2 mGluRs. A, The group 2 mGluR antagonist MSOPPE (40 mm/5 μl;n = 12) completely blocks LTD, fromt = 90 min post-LFT when compared with vehicle-injected controls (n = 12).B, Original analog traces showing evoked responses in the CA1 region at three time points: preinjection,t = 5 min, and t = 4 hr post-LFT, in an animal injected with MSOPPE (40 mm/5 μl).C, Dose–response curve for the antagonist effect of MSOPPE (4–80 mm/5 μl) on LTD in the CA1 region. The values represent the magnitude of LTD observed at 4 hr post-LFT.D, The group 2 mGluR antagonist EGLU (n = 6) completely blocks LTD, fromt = 75 min post-LFT when compared with vehicle-injected controls (n = 11). *p < 0.05, **p < 0.01, ***p < 0.001. Line breaks(//) indicate change in time scale.

  • Fig. 5.
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    Fig. 5.

    Group 1 and 2 mGluRs contribute to maintenance rather than initiation of LTD. A, Application of MSOPPE (40 mm/5 μl; n = 5) 5 min after LFT results in a significant inhibition of LTD, fromt = 105 min post-LFT compared with vehicle-injected controls (n = 5). B, Application of a subthreshold concentration of MSOPPE (20 mm/5 μl) in conjunction with 4CPG (20 mm/5 μl;n = 5) 5 min post-LFT results in a complete block of the 4CPG-resistant fraction of LTD, from t = 105 min compared with vehicle-injected controls (n = 5).

  • Fig. 6.
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    Fig. 6.

    LTP induction does not depend on activation of group 2 mGluRs. A, The group 2 mGluR antagonist MSOPPE (n = 7) does not inhibit LTP in the CA1 region when compared with vehicle-injected controls (n = 6).B, Original analog traces showing evoked responses in the CA1 region at three time points: preinjection,t = 5 min, and t = 4 hr post-HFT, in an animal injected with MSOPPE (40 mm/5 μl). Line breaks (//) indicate change in time scale.

  • Fig. 7.
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    Fig. 7.

    LTD but not LTP depends on activation of group 2 mGluRs. A, HFT in the presence of a vehicle injection (n = 5) results in a marked potentiation of fEPSP. LFT applied 1 hr after HFT causes evoked potentials to return to baseline values. MSOPPE (n = 5) applied before an identical protocol results in an LTP that cannot be reversed by application of LFT. B, Original analog traces showing evoked responses in the CA1 region at three time points: preinjection,t = 60 min, and t = 4 hr post-tetanus, in (1) an animal injected with MSOPPE (40 mm/5 μl) in which HFT is followed 1 hr later by LFT, and (2) an animal injected with MSOPPE (40 mm/5 μl) in which LFT is followed 1.5 hr later by HFT. C, Vehicle injection (n = 6) before LFT results in a marked depression of fEPSP. HFT applied 1.5 hr after LFT results in a reversal of depression to approximately pre-LFT values. MSOPPE (n = 6) applied before LFT results in a depression of LFT that recovers gradually. Application of HFT 1.5 hr after LFT produces a marked potentiation of fEPSP to LTP levels.Line breaks (//) indicate change in time scale.

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The Journal of Neuroscience: 17 (9)
Journal of Neuroscience
Vol. 17, Issue 9
1 May 1997
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Group 1 and 2 Metabotropic Glutamate Receptors Play Differential Roles in Hippocampal Long-Term Depression and Long-Term Potentiation in Freely Moving Rats
Denise Manahan-Vaughan
Journal of Neuroscience 1 May 1997, 17 (9) 3303-3311; DOI: 10.1523/JNEUROSCI.17-09-03303.1997

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Group 1 and 2 Metabotropic Glutamate Receptors Play Differential Roles in Hippocampal Long-Term Depression and Long-Term Potentiation in Freely Moving Rats
Denise Manahan-Vaughan
Journal of Neuroscience 1 May 1997, 17 (9) 3303-3311; DOI: 10.1523/JNEUROSCI.17-09-03303.1997
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Keywords

  • metabotropic glutamate receptors
  • long-term depression
  • long-term potentiation
  • in vivo
  • hippocampus
  • NMDA receptors

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