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  1. Article: Inhibition of the Interaction Between Group I Metabotropic Glutamate Receptors and PDZ-Domain Proteins Prevents Hippocampal Long-Term Depression, but Not Long-Term Potentiation.

    Neyman, Sergey / Braunewell, Karl-Heinz / O'Connell, Kara E / Dev, Kumlesh K / Manahan-Vaughan, Denise

    Frontiers in synaptic neuroscience

    2019  Volume 11, Page(s) 13

    Abstract: The group I metabotropic glutamate (mGlu) receptor subtypes, mGlu1 and mGlu5, strongly regulate hippocampal synaptic plasticity. Both harbor PSD-95/discs-large/ZO-1 (PDZ) motifs at their extreme carboxyl terminals, which allow interaction with the PDZ ... ...

    Abstract The group I metabotropic glutamate (mGlu) receptor subtypes, mGlu1 and mGlu5, strongly regulate hippocampal synaptic plasticity. Both harbor PSD-95/discs-large/ZO-1 (PDZ) motifs at their extreme carboxyl terminals, which allow interaction with the PDZ domain of Tamalin, regulate the cell surface expression of group I mGlu receptors, and may modulate their coupling to signaling proteins. We investigated the functional role of this interaction in hippocampal long-term depression (LTD). Acute intracerebral treatment of adult rats with a cell-permeable PDZ-blocking peptide (pep-mGluR-STL), designed to competitively inhibit the interaction between Tamalin and group 1 mGlu receptors, prevented expression of LTD in the hippocampal CA1 region without affecting long-term potentiation (LTP) or basal synaptic transmission. Pep-mGluR-STL prevented facilitation by the group I mGlu receptor agonist, (S)-3,5-Dihydroxyphenylglycine (DHPG), and the mGlu5 agonist, (R,S)-2-chloro-5-Hydroxyphenylglycine (CHPG), of short-term depression (STD) into LTD, suggesting that Tamalin preferentially acts by mediating signaling through mGlu5. These data support that Tamalin is essential for the persistent expression of LTD and that it subserves the effective signaling of group 1 mGlu receptors.
    Language English
    Publishing date 2019-04-18
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2592086-8
    ISSN 1663-3563
    ISSN 1663-3563
    DOI 10.3389/fnsyn.2019.00013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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

    Neyman, Sergey / Manahan-Vaughan, Denise

    The European journal of neuroscience

    2008  Volume 27, Issue 6, Page(s) 1345–1352

    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 ... ...

    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.
    MeSH term(s) Animals ; Excitatory Amino Acid Agonists/pharmacology ; Excitatory Amino Acid Antagonists/pharmacology ; Hippocampus/drug effects ; Hippocampus/physiology ; Long-Term Potentiation/drug effects ; Long-Term Potentiation/physiology ; Long-Term Synaptic Depression/drug effects ; Long-Term Synaptic Depression/physiology ; Male ; Neuronal Plasticity/drug effects ; Neuronal Plasticity/physiology ; Rats ; Rats, Wistar ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate/antagonists & inhibitors ; Receptors, Metabotropic Glutamate/physiology
    Chemical Substances Excitatory Amino Acid Agonists ; Excitatory Amino Acid Antagonists ; Grm5 protein, rat ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate ; metabotropic glutamate receptor type 1
    Language English
    Publishing date 2008-03-25
    Publishing country France
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 645180-9
    ISSN 1460-9568 ; 0953-816X
    ISSN (online) 1460-9568
    ISSN 0953-816X
    DOI 10.1111/j.1460-9568.2008.06109.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: MGluR5 mediates the interaction between late-LTP, network activity, and learning.

    Bikbaev, Arthur / Neyman, Sergey / Ngomba, Richard Teke / Conn, P Jeffrey / Conn, Jeffrey / Nicoletti, Ferdinando / Manahan-Vaughan, Denise

    PloS one

    2008  Volume 3, Issue 5, Page(s) e2155

    Abstract: Hippocampal synaptic plasticity and learning are strongly regulated by metabotropic glutamate receptors (mGluRs) and particularly by mGluR5. Here, we investigated the mechanisms underlying mGluR5-modulation of these phenomena. Prolonged pharmacological ... ...

    Abstract Hippocampal synaptic plasticity and learning are strongly regulated by metabotropic glutamate receptors (mGluRs) and particularly by mGluR5. Here, we investigated the mechanisms underlying mGluR5-modulation of these phenomena. Prolonged pharmacological blockade of mGluR5 with MPEP produced a profound impairment of spatial memory. Effects were associated with 1) a reduction of mGluR1a-expression in the dentate gyrus; 2) impaired dentate gyrus LTP; 3) enhanced CA1-LTP and 4) suppressed theta (5-10 Hz) and gamma (30-100 Hz) oscillations in the dentate gyrus. Allosteric potentiation of mGluR1 after mGluR5 blockade significantly ameliorated dentate gyrus LTP, as well as suppression of gamma oscillatory activity. CA3-lesioning prevented MPEP effects on CA1-LTP, suggesting that plasticity levels in CA1 are driven by mGluR5-dependent synaptic and network activity in the dentate gyrus. These data support the hypothesis that prolonged mGluR5-inactivation causes altered hippocampal LTP levels and network activity, which is mediated in part by impaired mGluR1-expression in the dentate gyrus. The consequence is impairment of long-term learning.
    MeSH term(s) Allosteric Regulation ; Animals ; Dentate Gyrus/drug effects ; Dentate Gyrus/physiology ; Excitatory Amino Acid Antagonists/pharmacology ; Learning ; Long-Term Potentiation ; Male ; Memory ; Pyridines/pharmacology ; Rats ; Rats, Wistar ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate/antagonists & inhibitors ; Receptors, Metabotropic Glutamate/physiology
    Chemical Substances Excitatory Amino Acid Antagonists ; Grm5 protein, rat ; Pyridines ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate ; 6-methyl-2-(phenylethynyl)pyridine (7VC0YVI27Y)
    Language English
    Publishing date 2008-05-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0002155
    Database MEDical Literature Analysis and Retrieval System OnLINE

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