The group I mGlu receptor agonist DHPG induces a novel form of LTD in the CA1 region of the hippocampus

Palmer, Mary J.; Irving, Andrew J.; Seabrook, Guy R.; Jane, David E.; Collingridge, Graham L.

doi:10.1016/s0028-3908(97)00181-0

Cited by 303 publications

(290 citation statements)

References 33 publications

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“…1D). These results, which are similar to previous findings in juvenile rat hippocampal slices (19,20), confirm that activation of mGluR5 is required for the induction of DHPG-LTD.…”

Section: Dhpg-induced An Mglur5-dependent Ltd-using Field Po-supporting

confidence: 92%

See 1 more Smart Citation

Rap1-induced p38 Mitogen-activated Protein Kinase Activation Facilitates AMPA Receptor Trafficking via the GDI·Rab5 Complex

Huang

You

et al. 2004

Journal of Biological Chemistry

163

198

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Recent evidence has emphasized the importance of p38 mitogen-activated protein kinase (MAPK) in the induction of metabotropic glutamate receptor (mGluR)-dependent long term depression (LTD) at hippocampal CA3-CA1 synapses. However, the cascade responsible of mGluR to activate p38 MAPK and the signaling pathway immediately downstream from it to induce synaptic depression is poorly understood. Here, we show that transient activation of group I mGluR with the selective agonist (S)-3,5-dihydroxyphenylglycine (DHPG) activates p38 MAPK through G protein ␤␥-subunit, small GTPase Rap1, and MAPK kinase 3/6 (MKK3/6), thus resulting in mGluR5-dependent LTD. Furthermore, our data clearly show that an accelerating AMPA receptor endocytosis by stimulating the formation of guanyl nucleotide dissociation inhibitor-Rab5 complex is a potential downstream processing of p38 MAPK activation to mediate DHPG-LTD. These results suggest an important role for Rap1-MKK3/6-p38 MAPK pathway in the induction of mGluR-dependent LTD by directly coupling to receptor trafficking machineries to facilitate the loss of synaptic AMPA receptors.Long term depression (LTD) 1 is a persistent activity-dependent decrease of synaptic efficacy that together with the converse process, long term potentiation, has been considered to be crucial for information storage in the brain (1, 2). In the hippocampus, LTD is divided into three categories: homosynaptic, heterosynaptic, and associative LTD (3). The bestcharacterized form of homosynaptic LTD is induced in the CA1 region of the hippocampus by prolonged low frequency synaptic stimulation via a NMDA receptor-dependent rise in postsynaptic [Ca 2ϩ ] i and the activation of serine/threonine protein phosphatases (4). Recent work has shown that mechanistically distinct type of LTD can be induced in the CA1 region by other types of synaptic stimulation or brief pharmacological treatments. For example, a prolonged period of paired-pulse stimulation or a direct application of the selective group I mGluR agonists, such as DHPG, can induce a robust mGluR-dependent form of LTD that is independent of NMDA receptor activation (5). In contrast to the mechanisms of NMDA receptor-dependent LTD, which are fairly well established, the mechanisms of induction and the site of expression of mGluR-dependent LTD are still a matter of some considerable debate. Current studies have reported that the induction of mGluR-dependent LTD does not require extracellular Ca 2ϩ (6), Ca 2ϩ release from intracellular stores (7), activation of Ca 2ϩ /calmodulin-dependent protein kinase II (8), protein kinase A or protein kinase C (7, 9), or serine/ threonine protein phosphatases (9). However, this form of LTD requires activation of G q -type G proteins (10), a local translation of dendritic mRNA (5, 11), a long-lasting loss of postsynaptic AMPA receptors (12, 13), and activation of protein tyrosine phosphatases (14). In addition, more recent studies suggest that p38 MAPK signaling also serves as a signal mediator in the induction of mGluR-depende...

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“…1D). These results, which are similar to previous findings in juvenile rat hippocampal slices (19,20), confirm that activation of mGluR5 is required for the induction of DHPG-LTD.…”

Section: Dhpg-induced An Mglur5-dependent Ltd-using Field Po-supporting

confidence: 92%

“…As reported previously (19,20), application of DHPG (50 M) for 5 min resulted in a substantial LTD of fEPSPs (DHPG-LTD). The synaptic responses were depressed to 63.5 Ϯ 5.1% (n ϭ 8; p Ͻ 0.05) measured at 40 min after washout of DHPG (Fig.…”

Section: Dhpg-induced An Mglur5-dependent Ltd-using Field Po-supporting

confidence: 73%

Rap1-induced p38 Mitogen-activated Protein Kinase Activation Facilitates AMPA Receptor Trafficking via the GDI·Rab5 Complex

Huang

You

et al. 2004

Journal of Biological Chemistry

163

198

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“…As described previously (Palmer et al, 1997;Oliet et al, 1997;Fitzjohn et al, 2001), brief application of DHPG caused an immediate depression of CA1 EPSP slope to 37 Ϯ 4% in control animals. After washout of DHPG, a longlasting reduction of EPSPs was observed (mGluR LTD, 60 Ϯ 6% of pre-DHPG baseline; n ϭ 6) ( Fig.…”

Section: Loss Of Mglur-induced Synaptic Depression After Status Epilesupporting

confidence: 57%

“…At the same synapses, a distinct form of LTD can be observed in the absence of functional NMDARs that requires the activation of metabotropic glutamate receptors (mGluRs) and relies on different expression mechanisms (Oliet et al, 1997). In the CA1 region, mGluR LTD can be readily induced by transient activation of postsynaptic group I mGluRs with a pharmacological agonist [for instance ( R,] (Palmer et al, 1997;Fitzjohn et al, 2001). During certain types of lowfrequency activity, activation of mGluRs by endogenously released glutamate also appears to result in mGluR-dependent, NMDAR-independent LTD with similar characteristics (Oliet et al, 1997;Kemp and Bashir, 1999;Huber et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Loss of Metabotropic Glutamate Receptor-Dependent Long-Term Depression via Downregulation of mGluR5 after Status Epilepticus

Kirschstein

Bauer²,

Müller³

et al. 2007

J. Neurosci.

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“…Accordingly, hippocampal LTD is significantly impaired in Arc/ Arg3.1 knockout mice, and these mice fail to form longlasting memories . mGluR-mediated LTD at CA1 synapses in the hippocampus can be induced by agonists selective for group I mGluRs (Palmer et al, 1997), relies on dendritic protein synthesis (Huber et al, 2000), and involves activation of MAPKs (Gallagher et al, 2004;Huang et al, 2004) and protein tyrosine phosphatases (Moult et al, 2002). mGluRinduced LTD is associated with a decrease of surface GluR1 AMPAR clusters (Snyder et al, 2001), and with tyrosine dephosphorylation of GluR2 AMPAR subunit (Moult et al, 2006).…”

Section: Role Of Ampars In Ltdmentioning

confidence: 99%

Regulation of AMPA receptors and synaptic plasticity

et al. 2009

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The group I mGlu receptor agonist DHPG induces a novel form of LTD in the CA1 region of the hippocampus

Cited by 303 publications

References 33 publications

Rap1-induced p38 Mitogen-activated Protein Kinase Activation Facilitates AMPA Receptor Trafficking via the GDI·Rab5 Complex

Rap1-induced p38 Mitogen-activated Protein Kinase Activation Facilitates AMPA Receptor Trafficking via the GDI·Rab5 Complex

Loss of Metabotropic Glutamate Receptor-Dependent Long-Term Depression via Downregulation of mGluR5 after Status Epilepticus

Regulation of AMPA receptors and synaptic plasticity

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