Coactivation of metabotropic and NMDA receptors is required for LTP induction

Musgrave, Melinda A.; Ballyk, Barbara A.; Goh, Joanne W.

doi:10.1097/00001756-199302000-00014

Cited by 55 publications

(25 citation statements)

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“…Further support for the present coactivation theory is the finding that a potentiation lasting 15 min was produced in CA1 when NMDA and ACPD were coapplied, although not when applied separately (Musgrave et al, 1993). A relatively fast onset LTP of intracellular EPSPs (peak attained in 30 min) induced by ACPD has also previously been observed in the dorsolateral septal nucleus, although tetanically induced LTP is not dependent on NMDAR activation in that nucleus (Zheng and Gallagher, 1992).…”

Section: Discussionsupporting

confidence: 73%

Tetanically induced LTP involves a similar increase in the AMPA and NMDA receptor components of the excitatory postsynaptic current: investigations of the involvement of mGlu receptors

1995

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Whole-cell patch-clamp recordings of evoked excitatory postsynaptic currents (EPSCs) were made from granule cells of the rat dentate gyrus in vitro. Tetanic stimulation in control media evoked a statistically identical long-term potentiation (LTP) of both the AMPA and NMDA receptor-mediated components of the dual component EPSC (AM-PAR and NMDAR EPSCs), as shown by a similar percentage increase in both components when measured at a holding potential of -30 mV, and also by an identical time course of the pre- and post-LTP induced EPSC at -30 mV and -70 mV. Application of the selective metabotropic glutamate receptor (mGluR) agonist 1S,3R-ACPD induced a transient depression followed by a rapid onset LTP of both the AMPAR and the NMDAR components of the dual component EPSC. The ACPD- and tetanically induced LTP of the AMPAR EPSC was NMDAR dependent, being abolished by the NMDAR antagonist AP5. Tetanic stimulation, and application of ACPD, also induced a relatively rapid onset LTP of the pharmacologically isolated NMDAR EPSC. Such tetanically and ACPD-induced LTP of the isolated NMDAR EPSC was also dependent on NMDAR activation, being strongly inhibited by AP5. The tetanically and the ACPD-induced LTP of the NMDAR EPSC were dependent on protein kinase C (PKC) stimulation, being strongly inhibited by the PKC inhibitor PKCI (19–31). The studies suggest that coactivation of the mGluR and NMDAR are required for induction of LTP of both the AMPAR- and NMDAR-mediated synaptic transmission. Moreover, LTP of the NMDAR-mediated synaptic transmission appears to be dependent on coincident activation of the NMDAR and mGluR.

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Section: Discussionsupporting

confidence: 73%

Tetanically induced LTP involves a similar increase in the AMPA and NMDA receptor components of the excitatory postsynaptic current: investigations of the involvement of mGlu receptors

1995

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“…Biochemical analysis at this point cannot separate out receptor subtypes mediating the PI turnover or even types of cells involved, e.g., neurons or glia. Electrophysiological studies using this compound have reported both success (Izumi et al, 1991) and failure (Stanton et al, 1991;Musgrave et al, 1993) in blocking tetanus-induced LTP. Behnisch and Reymann (1993) have reported that potentiation lasting for -l h was elicited by tetani given in the presence of L -A P~, but that the potentiation decayed over the next hour.…”

Section: Discussionmentioning

confidence: 99%

Dendritic Ca²⁺ accumulations and metabotropic glutamate receptor activation associated with an n‐methyl‐d‐aspartate receptor‐independent long‐term potentiation in hippocampal CA1 neurons

Petrozzino

Connor

1994

Hippocampus

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Bathing hippocampal slices in the potassium channel blocker tetraethylammonium (TEA), while stimulating the Schaffer collaterals at a low frequency, induces Ca(2+)-dependent, N-methyl-D-aspartate (NMDA) receptor-independent long-term potentiation of synaptic transmission (LTPk) in CA1 neurons. We have combined ratio imaging of fura-2 and mag-fura-5 in hippocampal CA1 neurons with intracellular and field recordings to evaluate postsynaptic Ca2+ changes that occur in the induction of LTPk. Test stimuli were applied at 0.05 Hz to stratum radiatum in the presence of the NMDA receptor antagonists D,L-2-amino-5-phosphonovaleric acid (100 microM) or MK-801 (10 microM). During TEA exposure (15-25 mM; 10 min), cells fired prolonged action potentials both spontaneously and in response to test stimuli resulting in transient, micromolar Ca2+ accumulations in both somata and dendrites. The initial EPSP slope, measured 60 min after TEA wash-out, was potentiated to approximately 200% of control. The Ca2+ channel blocker nimodipine (10 microM) greatly reduced Ca2+ transients in both magnitude and duration and prevented LTPk induction. Pretreatment of slices with compounds that block metabotropic glutamate receptor (mGluR)-stimulated phosphoinositide hydrolysis, L-2-amino-3-phosphonopropionic acid (L-AP3, 50-200 microM) or L-aspartate-beta-hydroxamate (50-100 microM), as well as protein kinase C (PKC) inhibitors (sphingosine, 20 microM; RO-31-8220, 0.2 microM; or calphostin C, 2 microM) also blocked LTPk. Ca2+ transients were unaffected by L-AP3 or RO-31-8220. These findings suggest that Ca2+ influx through voltage-gated channels and co-activation of PKC by mGluRs are both necessary for induction of LTPk. Activation of mGluRs must also occur in NMDA receptor-dependent induction paradigms, but is possibly of lesser importance owing to the much greater gating of Ca2+ directly into the dendritic spines.

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“…This form of potentiation and electrically induced LTP are blocked by the antagonist, (RS)-e~-methyl-4-carboxyphenylglycine (MCPG) (Bashir et al 1993;Bortolotto and Collingridge 1993). Since then, replication of the effects elicited by both the agonist and the antagonist has been met with mixed success, where some have been able to replicate the results (Richter-Levin et al 1994;Manahan-Vaughan and Reymann 1995;Riedel et al 1995) and others report failure (Chinestra et al 1993;Manzoni et al 1994;Ben-Ari and Aniksztejn 1995;Selig et al 1995) or have shown the effect to be linked with other excitatory amino acid receptors (see Musgrave et al 1993;O'Connor et al 1994O'Connor et al , 1995Bortolotto and Collingridge 1995).…”

Section: Introductionmentioning

confidence: 99%

Alterations in the expression of specific glutamate receptor subunits following hippocampal LTP in vivo.

Thomas¹,

Davis²,

Hunt³

et al. 1996

Learning & Memory

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Quantitative in situ hybridization revealed that following the induction of hippocampal long-term potentiation (LTP) in the dentate gyms of freely moving rats, specific increases in the expression of the NR2B subunit of the N-methyl-D-aspartate (NMDA) receptor and mGluRlc, a short splice variant of the metabotropic glutamate receptors that are linked intracellularly to phospholipase C (PLC) and protein kinase C (PKC), were seen in the postsynaptic dentate granule cells. There were no changes in the expression of NR2A; NR2C and NR2D NMDA receptor subunits; or mGluRla, mGluRlb, mGluR5a, and mGluR5b PLC-associated metabotropic receptors. The elevations in NR2B and mGluRlc mRNA were delayed, occurring days after LTP induction. NR2B expression was enhanced significantly by 48 hr after LTP but was starting to decrease toward basal levels by 96 hr. The transient increase in the expression of NR2B mirrored the increase in the expression of PKC-sensitive isoforms of the NR1 subunits of the NMDA 4Corresponding author. receptor we observed previously (Thomas et al. 1994a). The increase in mGluRlc expression was more persistent, showing a significant increase 96 hr after LTP. This study demonstrates that not only are there changes in the expression of individual glutamate receptor subunits but the increases in their expression occur days after the induction of LTP and may reflect so-called late-onset genes that may be important for the maintenance of LTP.

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Coactivation of metabotropic and NMDA receptors is required for LTP induction

Cited by 55 publications

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Tetanically induced LTP involves a similar increase in the AMPA and NMDA receptor components of the excitatory postsynaptic current: investigations of the involvement of mGlu receptors

Tetanically induced LTP involves a similar increase in the AMPA and NMDA receptor components of the excitatory postsynaptic current: investigations of the involvement of mGlu receptors

Dendritic Ca²⁺ accumulations and metabotropic glutamate receptor activation associated with an n‐methyl‐d‐aspartate receptor‐independent long‐term potentiation in hippocampal CA1 neurons

Alterations in the expression of specific glutamate receptor subunits following hippocampal LTP in vivo.

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Coactivation of metabotropic and NMDA receptors is required for LTP induction

Cited by 55 publications

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Tetanically induced LTP involves a similar increase in the AMPA and NMDA receptor components of the excitatory postsynaptic current: investigations of the involvement of mGlu receptors

Tetanically induced LTP involves a similar increase in the AMPA and NMDA receptor components of the excitatory postsynaptic current: investigations of the involvement of mGlu receptors

Dendritic Ca2+ accumulations and metabotropic glutamate receptor activation associated with an n‐methyl‐d‐aspartate receptor‐independent long‐term potentiation in hippocampal CA1 neurons

Alterations in the expression of specific glutamate receptor subunits following hippocampal LTP in vivo.

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Dendritic Ca²⁺ accumulations and metabotropic glutamate receptor activation associated with an n‐methyl‐d‐aspartate receptor‐independent long‐term potentiation in hippocampal CA1 neurons