Metabotropic glutamate receptor-dependent long-term potentiation

doi:10.1016/j.neuropharm.2009.01.002

Neuropharmacology

Volume 56, Issue 4, March 2009, Pages 735-740

https://doi.org/10.1016/j.neuropharm.2009.01.002 Get rights and content

Abstract

The induction of the most common form of LTP is well known to involve activation of N-methyl-d-aspartate receptors. However, considerable evidence has also shown that certain forms of LTP induction at excitatory synapses onto both principle cells and interneurons are dependent on activation of metabotropic glutamate receptors (mGluRs). mGluR-dependent LTP occurs in widespread areas of the brain including the neocortex, hippocampus, striatum and nucleus accumbens. mGluR-dependent forms of LTP have been found to be diverse, involving activation of mGluR1 or mGluR5 and can be of AMPAR-mediated transmission or of NMDAR-mediated transmission. Furthermore, the mGluR-dependent LTP may involve activation of other receptors, in particular, activation of NMDAR, dopamine and adenosine receptors. mGluR-dependent LTP can be expressed presynaptically or postsynaptically, and can involve a range of intracellular mediators including protein kinase C (PKC) and protein kinase A (PKA), tyrosine kinase Src and nitric oxide (NO).

Introduction

A number of recent studies have shown that the induction of LTP involves activation of mGluRs, and this mini-review is an update of a previous review (Anwyl, 1999) detailing investigations of the role of mGluRs in the induction of LTP of both AMPAR-mediated transmission and LTP of NMDAR-mediated transmission. Evidence for an essential role of the activation of mGluRs in the induction of LTP of AMPAR-mediated transmission is particularly strong at excitatory synapses onto interneurons in the hippocampus and neocortex, for induction of LTP of AMPAR-mediated transmission at certain synapses to principal cells in the neocortex, and also for LTP of NMDAR-mediated transmission in the hippocampus. mGluRs have been also shown to have a modulatory or metaplastic role in LTP of AMPAR-mediated transmission at certain synapses to principal neurons in the hippocampus and neocortex.

The division in the review of LTP into AMPAR-mediated transmission and NMDAR-mediated transmission refers only to the specific measurements of these types of receptor-mediated transmission made in the studies, and not to mechanisms. Clearly, if LTP is presynaptically expressed, then LTP of both AMPAR-mediated transmission and NMDAR-mediated transmission would be likely to occur, although it is possible that LTP of AMPAR-mediated transmission could be accompanied by LTD of NMDAR-mediated transmission. However, measurements of LTP of the NMDAR component have not been made in most studies in which expression of LTP has been shown to be presynaptically mediated.

Common features of mGluR-dependent LTP are highlighted, including the induction of the LTP via activation of mGluR5 or mGluR1, the necessity for a rise in intracellular Ca²⁺ following Ca²⁺ influx via NMDAR, L-type Ca²⁺channels, TRP channels or release from intracellular stores, and also the involvement of several intracellular messenger pathways.

Section snippets

Interneurons

Many studies have found that the induction of LTP at excitatory synapses on interneurons in the hippocampus and neocortex is mGluR-dependent. Thus induction of LTP of AMPAR-mediated transmission at synapses onto O/A interneurons in the CA1 hippocampus was shown to be predominantly mGluR1α mediated (Perez et al., 2001, Lapointe et al., 2003) as induction of the LTP was blocked by the mGluR group I/II antagonists E4CPG, MCPG and the mGluR1 antagonist LY367385 (Perez et al., 2001). Furthermore,

Involvement of other receptors in mGluR-dependent LTP

Activation of NMDAR was required for certain types of mGluR-dependent LTP, including the induction of LTP of NMDAR-mediated transmission in principal cells of the hippocampus (O'Connor et al., 1995, Kwon and Castillo, 2008, Rebola et al., 2008) and corticostriatal AMPAR-LTP (Calabresi et al., 1992, Pawlak and Kerr, 2008), with antagonism of NMDAR preventing such LTP. In contrast, induction of LTP of AMPAR-mediated transmission in CA1 O/A interneurons (Perez et al., 2001), neocortical FS cells (

Dependency on Ca

An elevation of intracellular Ca²⁺ is required for mGluR-dependent LTP. Thus loading the cells postsynaptically with high BAPTA blocked both LTP of NMDAR-mediated transmission in principal cells of the hippocampus (Harney et al., 2006, Kwon and Castillo, 2008, Rebola et al., 2008) and LTP of AMPAR-mediated transmission in interneurons in the hippocampus (Ouardouz and Lacaille, 1995, Lapointe et al., 2003, Galvan et al., 2008) and neocortex (Sarihi et al., 2008). Interestingly, LTP of

Involvement of intracellular pathways

Activation of PKC was found to be essential for LTP of NMDAR-mediated transmission in principal cells of the hippocampus as the LTP was blocked by PKC inhibitors (O'Connor et al., 1995, Kwon and Castillo, 2008) and mimicked by a PKC activator which occluded LTP of NMDAR-mediated transmission (Kwon and Castillo, 2008). A PKC activator also rescued LTP of NMDAR-mediated transmission in mGluR5 mice (Jia et al., 1998). The tyrosine kinase Src, which is well known to be involved in upregulation of

Site of expression

The expression of LTP of NMDAR-mediated transmission in the hippocampus is postsynaptically mediated as it was not found to be associated with a change in paired pulse ratio or decrease in the coefficient of variation (CV) (Kwon and Castillo, 2008, Harney et al., 2008). Studies of paired pulse ratio and CV also demonstrated that corticostriatal LTP is expressed postsynaptically (Pawlak and Kerr, 2008), although evidence from studies of paired pulse ratio, CV and m'EPSCs showed that LTP of

Concluding remarks

mGluR-dependent LTP has now been firmly established to occur at many excitatory synapses in the brain. LTP of AMPAR-mediated transmission has been well established to be mGluR1-dependent in interneurons in the hippocampus, while LTP of NMDAR-mediated transmission has been well established to involve shown to be mGluR5-dependent. Interestingly, while the former is expressed presynaptically, the latter is expressed postsynaptically. The induction of mGluR-dependent LTP at most synapses requires a

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Mini-reviewMetabotropic glutamate receptor-dependent long-term potentiation

Abstract

Introduction

Section snippets

Interneurons

Involvement of other receptors in mGluR-dependent LTP

Dependency on Ca

Involvement of intracellular pathways

Site of expression

Concluding remarks

Brain Res. Brain Res. Rev.

Neuron

Neuropharmacology

Neuropharmacology

Brain Res.

J. Biol. Chem.

Neuron

Neuroscience

Pain

Neuron

Neuropharmacology

Brain Res.

Neurosci. Lett.

Long-term potentiation of NMDA receptor-mediated transmission in the rat hippocampus

Nature

Induction of LTP in the hippocampus needs synaptic activation of glutamate metabotropic receptors

Nature

Dopamine and cAMP-regulated phosphoprotein 32 kDa controls both striatal long-term depression and long-term potentiation, opposing forms of synaptic plasticity

J. Neurosci.

A critical role of the nitric oxide/cGMP pathway in corticostriatal long-term depression

J. Neurosci.

Long-term potentiation in the striatum is unmasked by removing the voltage-dependent magnesium block of NMDA receptor channels

Eur. J. Neurosci.

Dopaminergic control of synaptic plasticity in the dorsal striatum

Eur. J. Neurosci.

Evidence for NMDA and mGlu receptor-dependent long-term potentiation of mossy fibre–granule cell transmission in rat cerebellum

J. Neurophysiol.

Bidirectional Hebbian plasticity at hippocampal mossy fibre synapse on CA3 interneurons

J. Neurosci.

Corticostriatal LTP requires combined mGluR1 and mGluR5 activation

Neuropharmacology

The role of nitric oxide and GluR1 in presynaptic and postsynaptic components of neocortical potentiation

J. Neurosci.

Neocortical long-term potentiation and experience-dependent synaptic plasticity require α-calcium/calmodulin-dependent protein kinase II autophosphorylation

J. Neurosci.

Extrasynaptic NR2D-containing NMDARs are recruited to the synapse during LTP of NMDAR-EPSCs

J. Neurosci.

Long-term depression of NMDA receptor-mediated synaptic transmission is dependent on activation of metabotropic glutamate receptors and is altered to long-term potentiation by low intracellular calcium buffering

J. Neurosci.

Effects of the metabotropic glutamate receptor antagonist MCPG on phosphoinositide turnover and synaptic plasticity in visual cortex

J. Neurosci.

Mini-review
Metabotropic glutamate receptor-dependent long-term potentiation