Expression of metabotropic glutamate receptor 1 isoforms in the substantia nigra pars compacta of the rat

Kosinski, C.; Standaert, David G.; Testa, Claudia; Penney, John B.; Young, Anne B.

doi:10.1016/s0306-4522(97)00654-4

Cited by 53 publications

(35 citation statements)

References 45 publications

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“…The light mGluR1a labeling in rat SNc neurons is consistent with recent in situ hybridization data showing that the mGluR1a mRNA level is relatively low in rat SNc neurons that, on the other hand, display strong mRNA expression for the mGluR1d splice variant (Kosinski et al, 1998). It is unlikely that the differential intensity of mGluR1a labeling between the rat and monkey SNc is caused by technical differences in the tissue processing because both species were perfused with the same fixative and incubated with antibodies under similar conditions.…”

Section: Interspecies Differences In Mglur1a Expression Between Rats supporting

confidence: 88%

“…Group I mGluR mRNA and the receptor proteins are expressed in rat SNc and SNr neurons (Berthele et al, 1998;Kosinski et al, 1998;Testa et al, 1994Testa et al, , 1998. Furthermore, electrophysiological studies have demonstrated that metabotropic glutamatergic stimulation has myriad effects on the firing rate and firing pattern of neurons in both portions of the SN (Meltzer et al, 1997;Fiorello and Williams, 1998;Wigmore and Lacey, 1998;Marino et al, 1999).…”

Section: Abstract: Metabotropic; Glutamate; Receptor Internalizationmentioning

confidence: 99%

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Differential Subcellular Localization of mGluR1a and mGluR5 in the Rat and Monkey Substantia Nigra

2001

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Neurons in the rat substantia nigra (SN) are enriched in group I metabotropic glutamate receptor (mGluR) subtypes and respond to group I mGluR activation. To better understand the mechanisms by which mGluR1 and mGluR5 mediate these effects, the goal of this study was to elucidate the subsynaptic localization of these two receptor subtypes in the rat and monkey substantia nigra. At the light microscope level, neurons of the SN pars reticulata (SNr) displayed moderate to strong immunoreactivity for both mGluR1a and mGluR5 in rats and monkeys. However, mGluR1a labeling was much stronger in monkey than in rat SN pars compacta (SNc) neurons, whereas a moderate level of mGluR5 immunoreactivity was found in both species. At the electron microscope level, the immunoreactivity for both group I mGluR subtypes was primarily expressed postsynaptically, although light mGluR1a labeling was occasionally seen in axon terminals in the rat SNr. Immunogold studies revealed a striking difference in the subcellular distribution of mGluR1a and mGluR5 immunoreactivity in SNr and SNc neurons. Although the bulk of mGluR1a was attached to the plasma membrane, Ͼ80% of mGluR5 immunoreactivity was intracellular. Plasma membrane-bound immunoreactivity for group I mGluRs in both SNc and SNr neurons was mostly extrasynaptic or in the main body of symmetric, putative GABAergic synapses. On the other hand, asymmetric synapses either were nonimmunoreactive or displayed perisynaptic labeling. These data raise important questions about the trafficking, internalization, and potential functions of group I mGluRs at extrasynaptic sites or symmetric synapses in the substantia nigra. Key words: metabotropic; glutamate; receptor internalization; receptor trafficking; dopamine neurons; Parkinson's disease; immunogold methodThe substantia nigra pars reticulata (SNr) and the internal segment of the globus pallidus are the main output nuclei of the basal ganglia, whereas the SN pars compacta (SNc) is a group of dopaminergic neurons that project to the striatum. Both the SNr and SNc receive glutamatergic innervation from the subthalamic nucleus), cerebral cortex, and pedunculopontine tegmental nucleus (Wichmann and DeLong, 1998).The effects of glutamate in the CNS are mediated by activation of ionotropic and metabotropic receptors. Ionotropic receptors are ligand-gated cation channels that mediate fast excitatory neurotransmission, whereas metabotropic glutamate receptors (mGluRs) belong to a family of G-protein-coupled receptors that mediate modulatory effects of synaptic transmission by activation of a number of intracellular metabolic pathways. The family of mGluRs is subdivided into three groups (Conn and Pin, 1997). The group I mGluRs consist of mGluR1, mGluR5, and all their splice variants. These receptors are coupled to phosphoinositol hydrolysis and usually induce slow depolarization. On the other hand, group II (mGluR2,3) and group III (mGluR4,6,7,8) mGluRs are negatively coupled to adenylate cyclase and often induce presynaptic inhibition of trans...

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Section: Interspecies Differences In Mglur1a Expression Between Rats supporting

confidence: 88%

Section: Abstract: Metabotropic; Glutamate; Receptor Internalizationmentioning

confidence: 99%

Differential Subcellular Localization of mGluR1a and mGluR5 in the Rat and Monkey Substantia Nigra

2001

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“…Importantly, the observation that CPCCOEt fully blocks train-induced suppression of excitation is in agreement with a mGluR1-mediated effect (Batchelor et al, 1997;Guatteo et al, 1999;Litschig et al, 1999). In addition, the lack of effect of MPEP indicates that mGluR5 is not involved, which is consistent with the expression of the mGluR1 subtype in DA cells (Testa et al, 1994;Kosinski et al, 1998). Interestingly, it has been reported that tetanic stimulation of excitatory fibers induces slow mGluR1-mediated excitatory and inhibitory responses (Shen and Johnson, 1997;Fiorillo and Williams, 1998) accompanied by rapid increases in intracellular Ca 2ϩ attributable to mobilization from the intracellular stores (Fiorillo and Williams, 1998;Guatteo et al, 1999;Morikawa et al, 2000).…”

Section: Discussionsupporting

confidence: 66%

“…5B) (EPSC amplitude 83.7 Ϯ 4.3% of baseline; n ϭ 7; p Ͻ 0.002 vs control). Midbrain DA cells express group I mGluRs on their soma and dendrites (Kosinski et al, 1998). mGluR1 and mGluR5 subtypes belong to group I mGluRs; therefore, to differentiate between these two subtypes, we bath applied CPCCOEt (100 M) and MPEP (10 M), selective mGluR1 and mGluR5 antagonists, respectively.…”

Section: -Arachidonoyl-glycerol Is the Retrograde Messenger For Suppmentioning

confidence: 99%

Prefrontal Cortex Stimulation Induces 2-Arachidonoyl-Glycerol-Mediated Suppression of Excitation in Dopamine Neurons

Melis¹,

Perra²,

Muntoni³

et al. 2004

J. Neurosci.

230

179

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Endocannabinoids form a novel class of retrograde messengers that modulate short-and long-term synaptic plasticity. Depolarizationinduced suppression of excitation (DSE) and inhibition (DSI) are the best characterized transient forms of endocannabinoid-mediated synaptic modulation. Stimulation protocols consisting of long-lasting voltage steps to the postsynaptic cell are routinely used to evoke DSE-DSI. Little is known, however, about more physiological conditions under which these molecules are released in vitro. Moreover, the occurrence in vivo of such forms of endocannabinoid-mediated modulation is still controversial. Here we show that physiologically relevant patterns of synaptic activity induce a transient suppression of excitatory transmission onto dopamine neurons in vitro. Accordingly, in vivo endocannabinoids depress the increase in firing and bursting activity evoked in dopamine neurons by prefrontal cortex stimulation. This phenomenon is selectively mediated by the endocannabinoid 2-arachidonoyl-glycerol (2-AG), which activates presynaptic cannabinoid type 1 receptors. 2-AG synthesis involves activation of metabotropic glutamate receptors and Ca 2ϩ mobilization from intracellular stores. These findings indicate that dopamine neurons release 2-AG to shape afferent activity and ultimately their own firing pattern. This novel endocannabinoid-mediated self-regulatory role of dopamine neurons may bear relevance in the pathogenesis of neuropsychiatric disorders such as schizophrenia and addiction.

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“…Group 1 receptors (mGluR1 and mGluR5) are coupled to the stimulation of phosphatidylinositol (PI) hydrolysis/ Ca 2þ signal transduction pathway. Both mGluR1 and mGluR5 comprize splice variants (mGluR1␣, ␤, c, d, g and mGluR5a, b) that partially differ in their carboxyterminal (ct) tails (Conn & Pin 1997;Kosinski et al 1998). Group 2 (mGluR2 and mGluR3) and group 3 (mGluR4, mGluR6, mGluR7 and mGluR8) receptors are both linked to the inhibitory cyclic AMP cascade but differ in their selective agonists (Nakanishi & Masu 1994;Pin & Duvoisin 1995;Conn & Pin 1997).…”

Section: Introductionmentioning

confidence: 99%

Competitive interaction of Seven in absentia homolog‐1A and Ca²⁺/calmodulin with the cytoplasmic tail of group 1 metabotropic glutamate receptors

et al. 1999

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Background: Group 1 metabotropic glutamate receptors (mGluR1 and mGluR5) are coupled to inositol trisphosphate/Ca 2þ signaling via G proteins and play an important role in excitatory synaptic transmission. To explore the regulation of group 1 mGluR function, we applied the yeast two-hybrid system using the intracellular carboxy-terminal domain of group 1 mGluRs (group 1 ct-mGluRs) and attempted to identify novel protein-protein interactions of group 1 mGluRs.

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Expression of metabotropic glutamate receptor 1 isoforms in the substantia nigra pars compacta of the rat

Cited by 53 publications

References 45 publications

Differential Subcellular Localization of mGluR1a and mGluR5 in the Rat and Monkey Substantia Nigra

Differential Subcellular Localization of mGluR1a and mGluR5 in the Rat and Monkey Substantia Nigra

Prefrontal Cortex Stimulation Induces 2-Arachidonoyl-Glycerol-Mediated Suppression of Excitation in Dopamine Neurons

Competitive interaction of Seven in absentia homolog‐1A and Ca²⁺/calmodulin with the cytoplasmic tail of group 1 metabotropic glutamate receptors

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Expression of metabotropic glutamate receptor 1 isoforms in the substantia nigra pars compacta of the rat

Cited by 53 publications

References 45 publications

Differential Subcellular Localization of mGluR1a and mGluR5 in the Rat and Monkey Substantia Nigra

Differential Subcellular Localization of mGluR1a and mGluR5 in the Rat and Monkey Substantia Nigra

Prefrontal Cortex Stimulation Induces 2-Arachidonoyl-Glycerol-Mediated Suppression of Excitation in Dopamine Neurons

Competitive interaction of Seven in absentia homolog‐1A and Ca2+/calmodulin with the cytoplasmic tail of group 1 metabotropic glutamate receptors

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Competitive interaction of Seven in absentia homolog‐1A and Ca²⁺/calmodulin with the cytoplasmic tail of group 1 metabotropic glutamate receptors