Region-specific expression of subunits of ionotropic glutamate receptors (AMPA-type, KA-type and NMDA receptors) in the rat spinal cord with special reference to nociception

Furuyama, Tatsuo; Kiyama, Hiroshi; Sato, Kohji; Park, Hwan Tae; Maeno, Hiroshi; Takagi, Hiroshi; Tohyama, Masaya

doi:10.1016/0169-328x(93)90183-p

Cited by 176 publications

(97 citation statements)

References 52 publications

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“…NMDAR2C transcripts have not been detected (765,1145,1341 Assessment of the relative abundance of AMPA, KA, and NMDA receptors within spinal motoneuron pools is difficult, since most ICC and ISH studies do not simultaneously examine expression of all three receptor classes, nor do they assess labeling based on the summed expression of all receptor subunits. However, available data in rat indicate that AMPA ~ NMDA > KA (407,1257), whereas data in rabbit suggest that AMPA ~ KA > NMDA (120).…”

Section: A Glutamate: Ionotropic Actionsmentioning

confidence: 99%

“…NMDAR1 and -2A subunits and transcripts are strongly expressed in cervical and lumbar motoneurons in rat (407,765,977,979,984,1145) and mouse (1341), and NMDAR2A subunits are present in human (1078). The presence of NMDAR2B subunits remains uncertain as their localization with ICC in cervical spinal cord of rat is with an antibody that does not distinguish between NMDAR2A and -2B (977).…”

Section: A Glutamate: Ionotropic Actionsmentioning

confidence: 99%

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Synaptic Control of Motoneuronal Excitability

Rekling

Funk

Bayliss

et al. 2000

Physiological Reviews

532

482

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Movement, the fundamental component of behavior and the principal extrinsic action of the brain, is produced when skeletal muscles contract and relax in response to patterns of action potentials generated by motoneurons. The processes that determine the firing behavior of motoneurons are therefore important in understanding the transformation of neural activity to motor behavior. Here, we review recent studies on the control of motoneuronal excitability, focusing on synaptic and cellular properties. We first present a background description of motoneurons: their development, anatomical organization, and membrane properties, both passive and active. We then describe the general anatomical organization of synaptic input to motoneurons, followed by a description of the major transmitter systems that affect motoneuronal excitability, including ligands, receptor distribution, pre-and postsynaptic actions, signal transduction, and functional role. Glutamate is the main excitatory, and GABA and glycine are the main inhibitory transmitters acting through ionotropic receptors. These amino acids signal the principal motor commands from peripheral, spinal, and supraspinal structures. Amines, such as serotonin and norepinephrine, and neuropeptides, as well as the glutamate and GABA acting at metabotropic receptors, modulate motoneuronal excitability through pre-and postsynaptic actions. Acting principally via second messenger systems, their actions converge on common effectors, e.g., leak K + current, cationic inward current, hyperpolarization-activated inward current, Ca 2+ channels, or presynaptic release processes. Together, these numerous inputs mediate and modify incoming motor commands, ultimately generating the coordinated firing patterns that underlie muscle contractions during motor behavior.

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Section: A Glutamate: Ionotropic Actionsmentioning

confidence: 99%

Section: A Glutamate: Ionotropic Actionsmentioning

confidence: 99%

Synaptic Control of Motoneuronal Excitability

Rekling

Funk

Bayliss

et al. 2000

Physiological Reviews

532

482

View full text Add to dashboard Cite

show abstract

“…Previous immunohistochemical and in situ hybridization studies have suggested that GluR1 and GluR2 subunits are present throughout the dorsal horn, with highest levels in laminas I and II, that GluR2 is also present in the ventral horn, and that GluR3 and GluR4 are highly expressed in ventral horn, with moderate levels in deep dorsal horn and limited expression in the superficial laminas (Furuyama et al, 1993;Tölle et al, 1993;Tachibana et al, 1994;Jakowec et al, 1995a,b;Harris et al, 1996;Popratiloff et al, 1996Popratiloff et al, , 1998Morrison et al, 1998;Spike et al, 1998; Engelman et al, 1999; Shibata et al, 1999). Our findings after pepsin treatment are consistent with these reports (Fig.…”

Section: Laminar Distribution Of Ampa Subunitsmentioning

confidence: 99%

“…AMPA receptors have also been implicated in excitotoxicity and degeneration of motoneurons in amyotrophic lateral sclerosis (van Damme et al, 2002). mRNAs for all four subunits of the AMPA receptor (GluR1-4) have been identified in the spinal cord (Furuyama et al, 1993;Henley et al, 1993;Tölle et al, 1993Tölle et al, , 1995Jakowec et al, 1995b;Shibata et al, 1999). Although conventional immunocytochemical studies have been performed to detect AMPA subunits (Tachibana et al, 1994;Jakowec et al, 1995a;Popratiloff et al, 1996Popratiloff et al, , 1998Morrison et al, 1998;Spike et al, 1998), it is unlikely that these revealed receptors at glutamatergic synapses, because these are thought to be inaccessible due to extensive cross-linking of the protein meshwork of the synaptic cleft and postsynaptic density that results from aldehyde fixation (Baude et al, 1995;Ottersen and Landsend, 1997;Fritschy et al, 1998;Watanabe et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Widespread Expression of the AMPA Receptor GluR2 Subunit at Glutamatergic Synapses in the Rat Spinal Cord and Phosphorylation of GluR1 in Response to Noxious Stimulation Revealed with an Antigen-Unmasking Method

Nagy¹,

Al-Ayyan²,

Andrew³

et al. 2004

J. Neurosci.

112

154

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Glutamate, the principal excitatory neurotransmitter in the spinal cord, acts primarily through AMPA receptors. Although all four AMPA subunits are expressed by spinal neurons, we know little about their distribution at glutamatergic synapses. We used an antigenunmasking technique to reveal the synaptic distribution of glutamate receptor (GluR) 1-4 subunits with confocal microscopy. After pepsin treatment, punctate staining was seen with antibodies against each subunit: GluR2-immunoreactive puncta were distributed throughout the gray matter, whereas GluR1-immunoreactive puncta were restricted to the dorsal horn and were most numerous in laminas I-II. Punctate staining for GluR3 and GluR4 was found in all laminas but was weak in superficial dorsal horn. Colocalization studies showed that GluR2 was present at virtually all (98%) puncta that were GluR1, GluR3, or GluR4 immunoreactive and that most (Ͼ90%) immunoreactive puncta in laminas IV, V, and IX showed GluR2, GluR3, and GluR4 immunoreactivity.Evidence that these puncta represented synaptic receptors was obtained with electron microscopy and by examining the association of GluR2-and GluR1-immunoreactive puncta with glutamatergic boutons (identified with vesicular glutamate transporters or markers for unmyelinated afferents). The great majority (96%) of these boutons were associated with GluR2-immunoreactive puncta. Our findings suggest that GluR2 is almost universally present at AMPA-containing synapses, whereas GluR1 is preferentially associated with primary afferent terminals.We also found a substantial, rapid increase in staining for synaptic GluR1 subunits phosphorylated on the S845 residue in the ipsilateral dorsal horn after peripheral noxious stimulation. This finding demonstrates plastic changes, presumably contributing to central sensitization, at the synaptic level.

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“…[147][148][149] In addition, AMPA/KA receptor activation, through the continuous infusion of KA into the rat spinal subarachnoid space, induces a progressive and motor-selective behavioral deficit associated with a late loss of spinal MNs. 150 Further, immunohistochemistry and in situ hybridization studies have emphasized that healthy human and rodent MNs express lower [151][152][153][154][155] or even undetectable 156,157 GluR2 subunit mRNA and protein, suggesting that MN AMPA/KA GluR have a higher permeability to Ca 2+ , which could account for MN hyper-susceptibility to excitotoxicity. The situation is slightly different in vitro, as in rat MN cultures 158 and spinal cord tissues, 159 GluR2-containing receptor clusters were found to be more abundant than GluR2-lacking clusters.…”

Section: Differential Glur Expression and Vulnerability To Excitotoximentioning

confidence: 99%

Glutamate pathway implication in amyotrophic lateral sclerosis: what is the signal in the noise?

Verche¹,

Ikiz²,

Jacquier³

et al. 2010

JRLCR

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Abstract:The cause of the fatal motor neuron disease, amyotrophic lateral sclerosis (ALS), remains largely unknown. Most cases of ALS are sporadic and, for ∼20% of familial ALS patients, mutations in the superoxide dismutase-1 (SOD1) gene have been identified. Transgenic rodents overexpressing mutant SOD1 emulate the disease and constitute the best ALS animal model so far. Several lines of evidence suggest that ALS is a multifactorial condition. In this review, we discuss the question of the involvement of the glutamate pathways in ALS-induced motor neuron death. As such, we review the data implicating glutamate metabolism alterations, glutamatergic environmental toxins, glutamate transporter/receptor defects, and Ca 2+ -mediated glutamate toxicity in the etiopathogenesis of ALS. Given the published data, we contend that glutamate-induced neurotoxicity more likely precipitates motor neuron degeneration rather than being the initiating factor of ALS. Furthermore, we propose that glutamate-induced neurotoxicity participates in the ALS deadly molecular cascade only as an executioner to put an end to a series of molecular perturbations that have irreversibly compromised motor neuron function. This could provide an explanation for the modest effect of therapeutic strategies targeting the glutamatergic system, including the only currently FDA-approved ALS treatment, riluzole. As in diseased motor neurons, overwhelming Ca 2+ overload may be the converging point for glutamate, endoplasmic reticulum stress, and mitochondrial dysfunctional pathways, and only therapies targeting these simultaneously or targeting the earliest alterations initiating this deleterious cascade may have a real impact on halting ALS progression.

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Region-specific expression of subunits of ionotropic glutamate receptors (AMPA-type, KA-type and NMDA receptors) in the rat spinal cord with special reference to nociception

Cited by 176 publications

References 52 publications

Synaptic Control of Motoneuronal Excitability

Synaptic Control of Motoneuronal Excitability

Widespread Expression of the AMPA Receptor GluR2 Subunit at Glutamatergic Synapses in the Rat Spinal Cord and Phosphorylation of GluR1 in Response to Noxious Stimulation Revealed with an Antigen-Unmasking Method

Glutamate pathway implication in amyotrophic lateral sclerosis: what is the signal in the noise?

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