Corticostriatal LTP requires combined mGluR1 and mGluR5 activation

Gubellini, Paolo; Saulle, Emilia; Centonze, Diego; Costa, Cinzia; Tropepi, Domenicantonio; Bernardi, Giorgio; Conquet, François; Calabresi, Paolo

doi:10.1016/s0028-3908(02)00214-9

Cited by 87 publications

(44 citation statements)

References 63 publications

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“…In ϳ50% of the recordings, HFS was delivered in the presence of 10 M bicuculline to block GABA A receptors. Consistently with previous reports (Calabresi et al, 2000;Gubellini et al, 2003), these experiments gave similar results to those obtained in the absence of this drug, and therefore all the data were pooled together.…”

Section: Methodssupporting

confidence: 87%

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Chronic Haloperidol Promotes Corticostriatal Long-Term Potentiation by Targeting Dopamine D2L Receptors

Centonze¹,

Usiello²,

Costa³

et al. 2004

J. Neurosci.

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Reduced glutamate-mediated synaptic transmission has been implicated in the pathophysiology of schizophrenia. Because antipsychotic agents might exert their beneficial effects against schizophrenic symptoms by strengthening excitatory transmission in critical dopaminoceptive brain areas, in the present study we have studied the effects of acute and chronic haloperidol treatment on striatal synaptic plasticity. Repetitive stimulation of corticostriatal terminals in slices induced either long-term depression or long-term potentiation (LTP) of excitatory transmission in control rats, whereas it invariably induced NMDA receptor-dependent LTP in animals treated chronically with haloperidol. Haloperidol effects were mimicked and occluded in mice lacking both D2L and D2S isoforms of dopamine D2 receptors (D2RϪ/Ϫ), in mice lacking D2L receptors and expressing normal levels of D2S receptors (D2RϪ/Ϫ;D2LϪ/Ϫ), and in mice lacking D2L receptors and overexpressing D2S receptors (D2LϪ/Ϫ). These data indicate that the blockade of D2L receptors was responsible for the LTP-favoring action of haloperidol in the striatum. In contrast, overexpression of D2S receptors uncovered a facilitatory role of this receptor isoform in LTP formation because LTP recorded from D2LϪ/Ϫ mice, but not those recorded from wild-type, D2RϪ/Ϫ, and D2RϪ/Ϫ;D2LϪ/Ϫ mice, was insensitive to the pharmacological blockade of D1 receptors.The identification of the cellular, molecular, and receptor mechanisms involved in the action of haloperidol in the brain is essential to understand how antipsychotic agents exert their beneficial and side effects.

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Section: Methodssupporting

confidence: 87%

“…Activation of protein kinase C (PKC) has been implicated in the molecular steps required to induce striatal LTP (Calabresi et al, 2000;Gubellini et al, 2003). Moreover, it has been reported that this kinase is stimulated by the activation of a subclass of D2 receptor (Choi et al, 1999).…”

Section: Role Of D2s Receptors In Striatal Synaptic Plasticitymentioning

confidence: 99%

Chronic Haloperidol Promotes Corticostriatal Long-Term Potentiation by Targeting Dopamine D2L Receptors

Centonze¹,

Usiello²,

Costa³

et al. 2004

J. Neurosci.

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“…The G q -coupled mGlu5 is highly expressed at excitatory synapses in the CA1 hippocampal neurons (Lujan et al, 1996) and contributes to a number of postsynaptic functions in the central nervous system, such as increased neuronal excitability, intracellular Ca 21 increase, synaptic plasticity, and pain (Snyder et al, 2001;Ireland and Abraham, 2002;Gubellini et al, 2003;Rae and Irving, 2004). Homer proteins are known to link mGluRs to other postsynaptic density proteins (Shiraishi-Yamaguchi and Furuichi, 2007;Niswender and Conn, 2010) and play a vital role in coupling the receptors with downstream effectors (Mao et al, 2005;Jung et al, 2007;Won et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Glutamate Delta-1 Receptor Regulates Metabotropic Glutamate Receptor 5 Signaling in the Hippocampus

et al. 2016

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The delta family of ionotropic glutamate receptors consists of glutamate delta-1 (GluD1) and glutamate delta-2 receptors. We have previously shown that GluD1 knockout mice exhibit features of developmental delay, including impaired spine pruning and switch in the N-methyl-D-aspartate receptor subunit, which are relevant to autism and other neurodevelopmental disorders. Here, we identified a novel role of GluD1 in regulating metabotropic glutamate receptor 5 (mGlu5) signaling in the hippocampus. Immunohistochemical analysis demonstrated colocalization of mGlu5 with GluD1 punctas in the hippocampus. Additionally, GluD1 protein coimmunoprecipitated with mGlu5 in the hippocampal membrane fraction, as well as when overexpressed in human embryonic kidney 293 cells, demonstrating that GluD1 and mGlu5 may cooperate in a signaling complex. The interaction of mGlu5 with scaffold protein effector Homer, which regulates mechanistic target of rapamycin (mTOR) signaling, was abnormal both under basal conditions and in response to mGlu1/5 agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) in GluD1 knockout mice. The basal levels of phosphorylated mTOR and protein kinase B, the signaling proteins downstream of mGlu5 activation, were higher in GluD1 knockout mice, and no further increase was induced by DHPG. We also observed higher basal protein translation and an absence of DHPG-induced increase in GluD1 knockout mice. In accordance with a role of mGlu5-mediated mTOR signaling in synaptic plasticity, DHPG-induced internalization of surface a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunits was impaired in the GluD1 knockout mice. These results demonstrate that GluD1 interacts with mGlu5, and loss of GluD1 impairs normal mGlu5 signaling potentially by dysregulating coupling to its effector. These studies identify a novel role of the enigmatic GluD1 subunit in hippocampal function.

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“…However, little is known about the adverse effects induced by long-term use of mGlu5 receptor antagonists. The permissive role of mGlu5 receptors in synaptic plasticity, learning, and memory (Lu et al, 1997;Jia et al, 1998Jia et al, , 2001Bortolotto et al, 1999;Doherty et al, 2000;Balschun and Wetzel, 2002;Petersen et al, 2002;Rodrigues et al, 2002;Gubellini et al, 2003) raises a major concern for the frequent association between parkinsonism and dementia (Korczyn, 2001;Mark, 2001). The clinical profile of mGlu2/3 receptor agonists is more established, and these drugs appear to be safe and suitable for longterm use in humans (Grillon et al, 2003;Holden, 2003).…”

Section: Discussionmentioning

confidence: 99%

Endogenous Activation of mGlu5 Metabotropic Glutamate Receptors Contributes to the Development of Nigro-Striatal Damage Induced by 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine in Mice

Battaglia¹,

Busceti²,

Molinaro³

et al. 2004

J. Neurosci.

116

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Corticostriatal LTP requires combined mGluR1 and mGluR5 activation

Cited by 87 publications

References 63 publications

Chronic Haloperidol Promotes Corticostriatal Long-Term Potentiation by Targeting Dopamine D2L Receptors

Chronic Haloperidol Promotes Corticostriatal Long-Term Potentiation by Targeting Dopamine D2L Receptors

Glutamate Delta-1 Receptor Regulates Metabotropic Glutamate Receptor 5 Signaling in the Hippocampus

Endogenous Activation of mGlu5 Metabotropic Glutamate Receptors Contributes to the Development of Nigro-Striatal Damage Induced by 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine in Mice

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