Evidence against a role for metabotropic glutamate receptors in mossy fiber LTP: the use of mutant mice and pharmacological antagonists

Hsia, Albert Y.; Salin, P. A.; Castillo, Pablo E.; Aiba, Atsu; Abeliovich, Asa; Tonegawa, Susumu

doi:10.1016/0028-3908(95)00115-m

Cited by 43 publications

(22 citation statements)

References 13 publications

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“…A train of stimuli that was subthreshold for the induction of LTP under normal conditions caused reliable induction of mossy fiber LTP when applied during inhibition of GABA B receptors with SCH50911 (10 M) (n ϭ 5). The same experimental protocol failed to reveal a shift in LTP threshold when using the mGluR antagonist MCPG (1.5 mM) (n ϭ 4, data not shown), as has been reported (30).…”

Section: Resultsmentioning

confidence: 49%

Glutamate and γ-aminobutyric acid mediate a heterosynaptic depression at mossy fiber synapses in the hippocampus

Vogt

1999

Proc. Natl. Acad. Sci. U.S.A.

164

128

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Mossy fiber synapses form the major excitatory input into the autoassociative network of pyramidal cells in the CA3 area of the hippocampus. Here we demonstrate that at the mossy fiber synapses, glutamate and ␥-aminobutyric acid (GABA) act as autaptic and heterosynaptic presynaptic inhibitory transmitters through metabotropic glutamate receptors (mGluRs) and GABA B receptors, respectively. Both GABA B receptors and mGluRs are activated through spillover from adjacent synapses. We demonstrate that glutamate spillover caused by brief tetanic activation of mossy fiber terminals remains intact at physiological temperatures. The activation of GABA B receptors increased the threshold for mossy fiber long-term potentiation (LTP), whereas activation of mGluRs did not have such an effect. We speculate that this heterosynaptic depression provides the mossy fiber synapses with a mechanism to efficiently shape input patterns into CA3, increasing the sparseness of the mossy fiber signal and enhancing the capacity and performance of the CA3 associative network. The increase in LTP threshold through activation of presynaptic inhibitory receptors imparts a piesynoptic associative nature to mossy fiber LTP.

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Section: Resultsmentioning

confidence: 49%

Glutamate and γ-aminobutyric acid mediate a heterosynaptic depression at mossy fiber synapses in the hippocampus

Vogt

1999

Proc. Natl. Acad. Sci. U.S.A.

164

128

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“…MCPG was shown to block the induction of mossy fiber LTP but not of post-tetanic potentiation (Bashir et al, 1993;Fitzjohn et al, 1998; but see Hsia et al, 1995). A small deficit in mossy fiber LTP was also reported in mice lacking mGlu1 (Conquet et al, 1994), but this was not confirmed in a subsequent study (Hsia et al, 1995).…”

Section: Distribution and Role Of Metabotropic Glutamate 1 Receptors mentioning

confidence: 95%

Metabotropic Glutamate 1 Receptor: Current Concepts and Perspectives

Ferraguti

Crepaldi

Nicoletti³

2008

Pharmacol Rev

192

205

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Almost 25 years after the first report that glutamate can activate receptors coupled to heterotrimeric G-proteins, tremendous progress has been made in the field of metabotropic glutamate receptors. Now, eight members of this family of glutamate receptors, encoded by eight different genes that share distinctive structural features have been identified. The first cloned receptor, the metabotropic glutamate ( mGlu) receptor mGlu1 has probably been the most extensively studied mGlu receptor, and in many respects it represents a prototypical subtype for this family of receptors. Its biochemical, anatomical, physiological, and pharmacological characteristics have been intensely investigated. Together with subtype 5, mGlu1 receptors constitute a subgroup of receptors that couple to phospholipase C and mobilize Ca(2+) from intracellular stores. Several alternatively spliced variants of mGlu1 receptors, which differ primarily in the length of their C-terminal domain and anatomical localization, have been reported. Use of a number of genetic approaches and the recent development of selective antagonists have provided a means for clarifying the role played by this receptor in a number of neuronal systems. In this article we discuss recent advancements in the pharmacology and concepts about the intracellular transduction and pathophysiological role of mGlu1 receptors and review earlier data in view of these novel findings. The impact that this new and better understanding of the specific role of these receptors may have on novel treatment strategies for a variety of neurological and psychiatric disorders is considered

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“…It was shown previously that mGluRs are significantly involved in the induction of LFS-induced depotentiation in the dentate gyrus (Kulla et al, 1999) and CA1 region of the hippocampus (but see Selig et al, 1995). Moreover, based on experiments using mutant mice and pharmacological antagonists, it has been proposed that mGluRs play a pivotal role in mediating the induction and expression of mossy fiber LTP and LTD (Conquet et al, 1994;Kobayashi et al, 1996;Yokoi et al, 1996) (but see Hsia et al, 1995), but it has not been demonstrated previously that depotentiation is also mediated by the mGluR activation. Given that LFS-induced depotentiation was prevented by the nonselective group 2 mGluR antagonist MCPG and selective group 2 mGluR antagonist LY341495 and was mimicked by bath-applied potent group 2 mGluR agonist DCG-IV, we suggest that activation of group 2 mGluRs may contribute to the induction of mossy fiber depotentiation.…”

Section: Discussionmentioning

confidence: 99%

Time-Dependent Reversal of Long-Term Potentiation by Low-Frequency Stimulation at the Hippocampal Mossy Fiber–CA3 Synapses

Chen

Huang

2001

J. Neurosci.

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Using mouse hippocampal slices, we studied the induction of depotentiation of long-term potentiation (LTP) at the mossy fiber synapses onto CA3 pyramidal neurons. A long train of low-frequency (1 Hz/900 pulses) stimulation (LFS) induced a long-term depression of baseline synaptic transmission or depotentiation of previously established LTP, which was reversible and was independent of NMDA receptor activation. This LFSinduced depotentiation was observed when the stimulus was delivered 1 or 10 min after LTP induction. However, when LFS was applied at 30 min after induction, significantly less depotentiation was found. The induction of depotentiation on one input was associated with a heterosynaptic reverse of the LTP induced previously on a separate pathway. In addition, this LFS-induced depotentiation appeared to be mediated by the activation of group 2 metabotropic glutamate receptors (mGluRs), because it was mimicked by the bath-applied group 2 agonist (2S,2ЈR,3ЈR)-2-(2Ј, 3Ј-dicarboxycyclopropyl) glycine and was specifically inhibited by the group 2 antagonists (S)-␣-methyl-4-carboxyphenylglycine and (␣S)-␣-amino-␣-(1S,2S)-2-carboxycyclopropyl-9H-xanthine-9-propanic acid. Moreover, the induction of depotentiation was entirely normal when synaptic transmission is blocked by glutamate receptor antagonist kynurenic acid and was associated with a reversal of pairedpulse facilitation attenuation during LTP expression. Pretreatment of the hippocampal slices with G i/o -protein inhibitor pertussis toxin (PTX) prevented the LFS-induced depotentiation. These results suggest that the activation of presynaptic group 2 mGluRs and in turn triggering a PTX-sensitive G i/o -proteincoupled signaling cascade may contribute to the LFS-induced depotentiation at the mossy fiber-CA3 synapses. Key words: long-term potentiation (LTP); long-term depression (LTD); depotentiation; metabotropic glutamate receptor (mGluR); mossy fiber pathway; hippocampusLong-term potentiation (LTP), a persistent increase in the efficacy of synaptic transmission induced by brief high-frequency stimulation of afferent pathways, has been considered to be an important component of the cellular basis of learning and memory in the brain (Bliss and Collingridge, 1993). However, the very persistence of LTP is itself problematical, because it could lead to a saturation of all modifiable synapses in a potentiated state, making them impossible to store additional new information. Thus, theoretical work has proposed that, in addition to a process such as LTP, there must also be existing mechanisms for counteracting enduring synaptic potentiation (Sejnowksi, 1977;Bienenstock et al., 1982;Wilshaw and Dayan, 1990). Until relatively recently, the idea of a depressive counterpart to LTP has become increasingly apparent, partly because considerable experimental evidence has been obtained that LTP can be reversed by various manipulations when administered within several minutes after LTP induction. For example, it has been shown that a brief period of hypoxia or applicatio...

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Evidence against a role for metabotropic glutamate receptors in mossy fiber LTP: the use of mutant mice and pharmacological antagonists

Cited by 43 publications

References 13 publications

Glutamate and γ-aminobutyric acid mediate a heterosynaptic depression at mossy fiber synapses in the hippocampus

Glutamate and γ-aminobutyric acid mediate a heterosynaptic depression at mossy fiber synapses in the hippocampus

Metabotropic Glutamate 1 Receptor: Current Concepts and Perspectives

Time-Dependent Reversal of Long-Term Potentiation by Low-Frequency Stimulation at the Hippocampal Mossy Fiber–CA3 Synapses

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