To see the other types of publications on this topic, follow the link: NMDA receptors and metabotropic glutamate receptors.
Journal articles on the topic 'NMDA receptors and metabotropic glutamate receptors'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'NMDA receptors and metabotropic glutamate receptors.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Sharp, Christopher D., I. Hines, J. Houghton, A. Warren, T. H. Jackson, A. Jawahar, A. Nanda, et al. "Glutamate causes a loss in human cerebral endothelial barrier integrity through activation of NMDA receptor." American Journal of Physiology-Heart and Circulatory Physiology 285, no. 6 (December 2003): H2592—H2598. http://dx.doi.org/10.1152/ajpheart.00520.2003.
Full textAbstract:
l-Glutamate is a major excitatory neurotransmitter that binds ionotropic and metabotropic glutamate receptors. Cerebral endothelial cells from many species have been shown to express several forms of glutamate receptors; however, human cerebral endothelial cells have not been shown to express either the N-methyl-d-aspartate (NMDA) receptor message or protein. This study provides evidence that human cerebral endothelial cells express the message and protein for NMDA receptors. Human cerebral endothelial cell monolayer electrical resistance changes in response to glutamate receptor agonists, antagonists, and second message blockers were tested. RT-PCR and Western blot analysis were used to demonstrate the presence of the NMDA receptor. Glutamate and NMDA (1 mM) caused a significant decrease in electrical resistance compared with sham control at 2 h postexposure; this response could be blocked significantly by MK-801 (an NMDA antagonist), 8-( N,N-diethylamino)- n-octyl-3,4,5-trimethyoxybenzoate (an intracellular Ca2+antagonist), and N-acetyl-l-cystein (an antioxidant). Trans(±)-1-amino-1,3-cyclopentanedicarboxylic acid, a metabotropic receptor agonist (1 mM), did not significantly decrease electrical resistance. Our results are consistent with a model where glutamate, at excitotoxic levels, may lead to a breakdown in the blood brain barrier via activation of NMDA receptors.
2
Li, De-Pei, David B. Averill, and Hui-Lin Pan. "Differential roles for glutamate receptor subtypes within commissural NTS in cardiac-sympathetic reflex." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 281, no. 3 (September 1, 2001): R935—R943. http://dx.doi.org/10.1152/ajpregu.2001.281.3.r935.
Full textAbstract:
Ischemic stimulation of cardiac receptors evokes excitatory sympathetic reflexes. Although the nucleus of the solitary tract (NTS) is an important site for integration of visceral afferents, its involvement in the cardiac-renal sympathetic reflex remains to be fully defined. This study examined the role of glutamate receptor subtypes in the commissural NTS in the sympathetic responses to stimulation of cardiac receptors. Renal sympathetic nerve activity (RSNA) was recorded in anesthetized rats. Cardiac receptors were stimulated by epicardial application of bradykinin (BK; 10 μg/ml). Application of BK significantly increased the mean arterial pressure from 78.2 ± 2.2 to 97.5 ± 2.9 mmHg and augmented RSNA by 38.5 ± 2.5% ( P < 0.05). Bilateral microinjection of 10 pmol of 6-cyano-7-nitroquinoxaline-2,3-dione, a non- N-methyl-d-aspartate (NMDA) antagonist, into the commissural NTS eliminated the pressor and RSNA responses to BK application in 10 rats. However, microinjection of 2-amino-5-phosphonopentanoic acid (0.1 and 1 nmol, n = 8), an NMDA- receptor antagonist, or α-methyl-4-carboxyphenylglycine (0.1 and 1 nmol, n = 5), a glutamate metabotropic receptor antagonist, failed to attenuate significantly the pressor and RSNA responses to stimulation of cardiac receptors with BK. Thus this study suggests that non-NMDA, but not NMDA and glutamate metabotropic, receptors in the commissural NTS play an important role in the sympathoexcitatory reflex response to activation of cardiac receptors during myocardial ischemia.
3
Bruno, Valeria, Giuseppe Battaglia, Agata Copani, Mara D'Onofrio, P. Di Iorio, Antonio De Blasi, Daniela Melchiorri, Peter J. Flor, and Ferdinando Nicoletti. "Metabotropic Glutamate Receptor Subtypes as Targets for Neuroprotective Drugs." Journal of Cerebral Blood Flow & Metabolism 21, no. 9 (September 2001): 1013–33. http://dx.doi.org/10.1097/00004647-200109000-00001.
Full textAbstract:
Metabotropic glutamate (mGlu) receptors have been considered as potential targets for neuroprotective drugs, but the lack of specific drugs has limited the development of neuroprotective strategies in experimental models of acute or chronic central nervous system (CNS) disorders. The advent of potent and centrally available subtype-selective ligands has overcome this limitation, leading to an extensive investigation of the role of mGlu receptor subtypes in neurodegeneration during the last 2 years. Examples of these drugs are the noncompetitive mGlu1 receptor antagonists, CPCCOEt and BAY-36-7620; the noncompetitive mGlu5 receptor antagonists, 2-methyl-6-(phenylethynyl)pyridine, SIB-1893, and SIB-1757; and the potent mGlu2/3 receptor agonists, LY354740 and LY379268. Pharmacologic blockade of mGlu1 or mGlu5 receptors or pharmacologic activation of mGlu2/3 or mGlu4/7/8 receptors produces neuroprotection in a variety of in vitro or in vivo models. MGlu1 receptor antagonists are promising drugs for the treatment of brain ischemia or for the prophylaxis of neuronal damage induced by synaptic hyperactivity. MGlu5 receptor antagonists may limit neuronal damage induced by a hyperactivity of N-methyl-d-aspartate (NMDA) receptors, because mGlu5 and NMDA receptors are physically and functionally connected in neuronal membranes. A series of observations suggest a potential application of mGlu5 receptor antagonists in chronic neurodegenerative disorders, such as amyotrophic lateral sclerosis and Alzheimer disease. MGlu2/3 receptor agonists inhibit glutamate release, but also promote the synthesis and release of neurotrophic factors in astrocytes. These drugs may therefore have a broad application as neuroprotective agents in a variety of CNS disorders. Finally, mGlu4/7/8 receptor agonists potently inhibit glutamate release and have a potential application in seizure disorders. The advantage of all these drugs with respect to NMDA or AMPA receptor agonists derives from the evidence that mGlu receptors do not “mediate,” but rather “modulate” excitatory synaptic transmission. Therefore, it can be expected that mGlu receptor ligands are devoid of the undesirable effects resulting from the inhibition of excitatory synaptic transmission, such as sedation or an impairment of learning and memory.
4
CHEN, QUAN, JOHN W. OLNEY, MADELON T. PRICE, and CARMELO ROMANO. "Biochemical and morphological analysis of non-NMDA receptor mediated excitotoxicity in chick embryo retina." Visual Neuroscience 16, no. 1 (January 1999): 131–39. http://dx.doi.org/10.1017/s095252389916108x.
Full textAbstract:
Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate glutamatergic neurotransmission, and when pathologically overstimulated induce excitotoxic neuronal death. Of the two families of iGluRs, the non-NMDA receptors have received less experimental attention than the NMDA receptors as mediators of neuronal death in in vitro systems. We have demonstrated that non-NMDA receptor activation is highly lethal for neurons of the chick embryo retina, and further characterize this phenomenon here. Treatment of isolated retinas with any of the non-NMDA receptor agonists glutamate, AMPA, or KA, in the presence of the NMDA receptor antagonist MK-801, led to pathomorphology and cell death. KA was the most effective toxin. All of KA-induced toxicity could be blocked by selective AMPA receptor blockers. The toxicity of both AMPA and glutamate could be greatly increased using cyclothiazide, which blocks AMPA receptor desensitization. These results indicate that KA is the most powerful toxin because it is a non-desensitizing agonist at the AMPA receptors. Glutamate exhibited a paradoxical ability to prevent KA-induced toxicity as measured by a biochemical assay of cell death. Also, histological studies indicated that glutamate selectively blocked KA-induced pathomorphological changes in bipolar cells. This protective effect of glutamate was not mimicked by AMPA, NMDA, or any of several metabotropic receptor agonists, indicating that it may be mediated by a receptor of undescribed pharmacology.
5
Nattie, E. E., and A. Li. "Rat retrotrapezoid nucleus iono- and metabotropic glutamate receptors and the control of breathing." Journal of Applied Physiology 78, no. 1 (January 1, 1995): 153–63. http://dx.doi.org/10.1152/jappl.1995.78.1.153.
Full textAbstract:
We injected 10 nl (unilateral) of glutamate receptor antagonists or agonists into the region of the retrotrapezoid nucleus and measured the phrenic nerve and blood pressure responses. The rats were chloralose-urethan anesthetized, paralyzed, vagotomized, and ventilated, and each injection location was verified anatomically. Integrated phrenic amplitude was most reliably affected. The N-methyl-D-aspartic acid (NMDA) antagonists 2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione (which affects both NMDA and non-NMDA receptors) both decreased baseline eucapnic phrenic amplitude and the CO2 response. Glutamate increased phrenic amplitude in a dose-dependent manner, an effect blocked by prior injection of the NMDA and non-NMDA antagonists at the same site. The response duration depended on the duration of the glutamate injection: responses to 3-s injections lasted a few minutes, and responses to 60-s injections lasted for > 30 min. The long-lasting effect was reproduced by injection of the metabotropic agonist 1(S),3(R)-aminocyclopentanedicarboxylic acid at 0.01–0.02 times the glutamate dose. We conclude that the rat retrotrapezoid nucleus has an endogenous source of glutamate that maintains eucapnic phrenic output and allows expression of the CO2 response. NMDA and possibly non-NMDA receptors are involved. Their stimulation increases phrenic output via ionotropic and metabotropic receptor processes with the latter resulting in long-lasting phrenic stimulation.
6
Zidichouski, J. A., J. C. Easaw, and J. H. Jhamandas. "Glutamate receptor subtypes mediate excitatory synaptic responses of rat lateral parabrachial neurons." American Journal of Physiology-Heart and Circulatory Physiology 270, no. 5 (May 1, 1996): H1557—H1567. http://dx.doi.org/10.1152/ajpheart.1996.270.5.h1557.
Full textAbstract:
We examined the role of specific excitatory amino acid (EAA) receptors in synaptic transmission within the lateral parabrachial nucleus (LPBN) using whole cell patch-recording techniques in a slice preparation. Two types of excitatory postsynaptic responses were observed. The first involved the contribution of non-N-methyl-D-aspartate (NMDA) receptors, which mediated a fast component, and NMDA receptors, which governed the late component of the excitatory postsynaptic current (EPSC). The second EPSC response was mediated solely by non-NMDA receptors. Both EPSC responses reversed near 0 mV. The fast component of the EPSC was attenuated by the non-NMDA antagonists [6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), 6,7-dinitroquinoxaline-2,3-dione (DNQX), and 6-nitro-7-sulfamobenzoquinoxaline-2-3,-dione (NBQX)]. The late component was reduced by D,L-2-amino-5-phosphonovaleric acid (APV) and augmented in Mg(2+)-free external medium. EPSCs mediated solely by non-NMDA receptors were completely blocked by CNQX and NBQX but not affected by APV or Mg(2+)-free external medium. EPSCs were also markedly attenuated by the metabotropic-receptor agonist, trans-(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (trans-ACPD). We concluded that intra-LPBN stimulation causes the synaptic release of glutamate, which depolarizes LBPN neurons via non-NMDA and NMDA receptors. We also provide evidence that glutamate can negatively influence its own release via action on presynaptic metabotropic receptors.
7
Jin, Xiao-Tao, Christopher J. Beaver, Qinghua Ji, and Nigel W. Daw. "Effect of the Group I Metabotropic Glutamate Agonist DHPG on the Visual Cortex." Journal of Neurophysiology 86, no. 4 (October 1, 2001): 1622–31. http://dx.doi.org/10.1152/jn.2001.86.4.1622.
Full textAbstract:
Metabotropic glutamate receptors have a variety of effects in visual cortex that depend on the age of the animal, the layer of the cortex, and the group of the receptor. Here we describe these effects for group I receptors, using both in vivo and in vitro preparations. The metabotropic group I glutamate receptor agonist 3,5 dihydroxyphenylglycine (DHPG) potentiates the responses to N-methyl-d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) in slices of rat visual cortex. It also increases, initially, the visual response in the cat visual cortex. Both these effects are largest at 3–4 wk of age and decline to insignificance by 10 wk of age. Both are also largest in lower layers of cortex, which explains why the facilitatory effects found with the general metabotropic glutamate agonist 1S,3R aminocyclopentane-1,3-dicarboxylic acid (ACPD) are observed only in lower layers. Prolonged application of DHPG in the cat visual cortex, after the initial excitatory effect, produces depression. We also found that DHPG facilitates the NMDA response in fast-spiking cells, which are inhibitory, providing a partial explanation for this. Thus there are multiple effects of group I metabotropic glutamate receptors, which vary with layer and age in visual cortex.
8
Lin, Weihong, and Sue C. Kinnamon. "Physiological Evidence for Ionotropic and Metabotropic Glutamate Receptors in Rat Taste Cells." Journal of Neurophysiology 82, no. 5 (November 1, 1999): 2061–69. http://dx.doi.org/10.1152/jn.1999.82.5.2061.
Full textAbstract:
Monosodium glutamate (MSG) elicits a unique taste in humans called umami. Recent molecular studies suggest that glutamate receptors similar to those in brain are present in taste cells, but their precise role in taste transduction remains to be elucidated. We used giga-seal whole cell recording to examine the effects of MSG and glutamate receptor agonists on membrane properties of taste cells from rat fungiform papillae. MSG (1 mM) induced three subsets of responses in cells voltage-clamped at −80 mV: a decrease in holding current (subset I), an increase in holding current (subset II), and a biphasic response consisting of an increase, followed by a decrease in holding current (subset III). Most subset II glutamate responses were mimicked by the ionotropic glutamate receptor (iGluR) agonist N-methyl-d-aspartate (NMDA). The current was potentiated by glycine and was suppressed by the NMDA receptor antagonist d(−)-2-amino-5-phosphonopentanoic acid (AP5). The group III metabotropic glutamate receptor (mGluR) agonistl-2-amino-4-phosphonobutyric acid (l-AP4) usually mimicked the subset I glutamate response. This hyperpolarizing response was suppressed by the mGluR antagonist (RS)-α-cyclopropyl-4-phosphonophenylglycine (CPPG) and by 8-bromo-cAMP, suggesting a role for cAMP in the transduction pathway. In a small subset of taste cells, l-AP4 elicited an increase in holding current, resulting in taste cell depolarization under current clamp. Taken together, our results suggest that NMDA-like receptors and at least two types of group III mGluRs are present in taste receptor cells, and these may be coactivated by MSG. Further studies are required to determine which receptors are located on the apical membrane and how they contribute to the umami taste.
9
Manahan-Vaughan, Denise. "Regulation of hippocampal information encoding by metabotopic glutamate receptors." Neuroforum 24, no. 3 (August 28, 2018): A121—A126. http://dx.doi.org/10.1515/nf-2018-a007.
Full textAbstract:
Abstract The hippocampus supports the acquisition of both spatial representations and long-term spatial memory. This is enabled by a triumvirate of physiological processes comprising information organisation and transfer by means of neuronal oscillations, creation of context-dependent spatial maps by means of place cells, and long-term storage of spatial experience by means of synaptic plasticity. All three processes are enabled by the glutamatergic system. Glutamate binding to ionotropic glutamate receptors enables both fast excitatory synaptic transmission (via AMPA receptors) and the initiation of long-term synaptic storage (via NMDA receptors). But glutamate also binds to metabotropic glutamate (mGlu) receptors. These receptors not only contribute to the stability of hippocampal encoding and the longevity of synaptic plasticity, they can also support synaptic information storage independent of NMDA receptor activation and are important for the acquisition and retention of long-term memory.
10
Hada, Binika, Mrigendra Bir Karmacharya, So R. Park, and Byung H. Choi. "Low-Intensity Ultrasound Decreases Ischemia-Induced Edema by Inhibiting N-Methyl-d-Aspartic Acid Receptors." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 45, no. 6 (November 2018): 675–81. http://dx.doi.org/10.1017/cjn.2018.331.
Full textAbstract:
AbstractBackground: We have previously shown that low-intensity ultrasound (LIUS), a noninvasive mechanical stimulus, inhibits brain edema formation induced by oxygen and glucose deprivation (OGD) or treatment with glutamate, a mediator of OGD-induced edema, in acute rat hippocampal slice model in vitro. Methods: In this study, we treated the rat hippocampal slices with N-methyl-d-aspartic acid (NMDA) or (S)-3,5-dihydroxyphenylglycine (DHPG) to determine whether these different glutamate receptor agonists induce edema. The hippocampal slices were then either sonicated with LIUS or treated with N-methyl-d-aspartic acid receptor (NMDAR) antagonists, namely, MK-801 and ketamine, and observed their effects on edema formation. Results: We observed that treatment with NMDA, an agonist of ionotropic glutamate receptors, induced brain edema at similar degrees compared with that induced by OGD. However, treatment with DHPG, an agonist of metabotropic glutamate receptors, did not significantly induce brain edema. Treatment with the NMDAR antagonists MK-801 or ketamine efficiently prevented brain edema formation by both OGD and NMDA in a concentration-dependent manner. N-Methyl-d-aspartic acid-induced brain edema was alleviated by LIUS in an intensity-dependent manner when ultrasound was administered at 30, 50, or 100 mW/cm2 for 20 minutes before the induction of the edema. Furthermore, LIUS reduced OGD- and NMDA-induced phosphorylation of NMDARs at Y1325. Conclusion: These results suggest that LIUS can inhibit OGD- or NMDA-induced NMDAR activation by preventing NMDAR phosphorylation, thereby reducing a subsequent brain edema formation. The mechanisms by which LIUS inhibits NMDAR phosphorylation need further investigation.
11
Gasparini, Fabrizio, Thérèse Di Paolo, and Baltazar Gomez-Mancilla. "Metabotropic Glutamate Receptors for Parkinson's Disease Therapy." Parkinson's Disease 2013 (2013): 1–11. http://dx.doi.org/10.1155/2013/196028.
Full textAbstract:
Excessive glutamatergic signalling within the basal ganglia is implicated in the progression of Parkinson’s disease (PD) and inthe emergence of dyskinesia associated with long-term treatment with L-DOPA. There is considerable research focus on the discovery and development of compounds that modulate glutamatergic signalling via glutamate receptors, as treatments for PD and L-DOPA-induced dyskinesia (LID). Although initial preclinical studies with ionotropic glutamate receptor antagonists showed antiparkinsonian and antidyskinetic activity, their clinical use was limited due to psychiatric adverse effects, with the exception of amantadine, a weak N-methyl-d-aspartate (NMDA) antagonist, currently used to reduce dyskinesia in PD patients. Metabotropic receptor (mGlu receptor) modulators were considered to have a more favourable side-effect profile, and several agents have been studied in preclinical models of PD. The most promising results have been seen clinically with selective antagonists of mGlu5 receptor and preclinically with selective positive allosteric modulators of mGlu4 receptor. The growing understanding of glutamate receptor crosstalk also raises the possibility of more precise modulation of glutamatergic transmission, which may lead to the development of more effective agents for PD.
12
Chianca, Deoclecio A., Li-Hsien Lin, Deidre Nitschke Dragon, and William T. Talman. "NMDA receptors in nucleus tractus solitarii are linked to soluble guanylate cyclase." American Journal of Physiology-Heart and Circulatory Physiology 286, no. 4 (April 2004): H1521—H1527. http://dx.doi.org/10.1152/ajpheart.00236.2003.
Full textAbstract:
We sought to test the hypothesis that cardiovascular responses to activation of ionotropic, but not metabotropic, glutamate receptors in the nucleus tractus solitarii (NTS) depend on soluble guanylate cyclase (sGC) and that inhibition of sGC would attenuate baroreflex responses to changes in arterial pressure. In adult male Sprague-Dawley rats anesthetized with chloralose, the ionotropic receptor agonists N-methyl-d-aspartate (NMDA) and dl-α-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA) and the metabotropic receptor agonist trans-dl-amino-1,3-cyclopentane-dicarboxylic acid (ACPD) were microinjected into the NTS before and after microinjection of sGC inhibitors at the same site. Inhibition of sGC produced significant dose-dependent attenuation of cardiovascular responses to NMDA but did not alter responses produced by injection of AMPA or ACPD. Bilateral inhibition of sGC did not alter arterial pressure, nor did it attenuate baroreflex responses to pharmacologically induced changes in arterial pressure. This study links sGC with NMDA, but not AMPA or metabotropic, receptors in cardiovascular signal transduction through NTS.
13
Moutin, Enora, Fabrice Raynaud, Jonathan Roger, Emilie Pellegrino, Vincent Homburger, Federica Bertaso, Vincent Ollendorff, Joël Bockaert, Laurent Fagni, and Julie Perroy. "Dynamic remodeling of scaffold interactions in dendritic spines controls synaptic excitability." Journal of Cell Biology 198, no. 2 (July 16, 2012): 251–63. http://dx.doi.org/10.1083/jcb.201110101.
Full textAbstract:
Scaffolding proteins interact with membrane receptors to control signaling pathways and cellular functions. However, the dynamics and specific roles of interactions between different components of scaffold complexes are poorly understood because of the dearth of methods available to monitor binding interactions. Using a unique combination of single-cell bioluminescence resonance energy transfer imaging in living neurons and electrophysiological recordings, in this paper, we depict the role of glutamate receptor scaffold complex remodeling in space and time to control synaptic transmission. Despite a broad colocalization of the proteins in neurons, we show that spine-confined assembly/disassembly of this scaffold complex, physiologically triggered by sustained activation of synaptic NMDA (N-methyl-d-aspartate) receptors, induces physical association between ionotropic (NMDA) and metabotropic (mGlu5a) synaptic glutamate receptors. This physical interaction results in an mGlu5a receptor–mediated inhibition of NMDA currents, providing an activity-dependent negative feedback loop on NMDA receptor activity. Such protein scaffold remodeling represents a form of homeostatic control of synaptic excitability.
14
Kryszkowski, Waldemar, and Tomasz Boczek. "The G Protein-Coupled Glutamate Receptors as Novel Molecular Targets in Schizophrenia Treatment—A Narrative Review." Journal of Clinical Medicine 10, no. 7 (April 2, 2021): 1475. http://dx.doi.org/10.3390/jcm10071475.
Full textAbstract:
Schizophrenia is a severe neuropsychiatric disease with an unknown etiology. The research into the neurobiology of this disease led to several models aimed at explaining the link between perturbations in brain function and the manifestation of psychotic symptoms. The glutamatergic hypothesis postulates that disrupted glutamate neurotransmission may mediate cognitive and psychosocial impairments by affecting the connections between the cortex and the thalamus. In this regard, the greatest attention has been given to ionotropic NMDA receptor hypofunction. However, converging data indicates metabotropic glutamate receptors as crucial for cognitive and psychomotor function. The distribution of these receptors in the brain regions related to schizophrenia and their regulatory role in glutamate release make them promising molecular targets for novel antipsychotics. This article reviews the progress in the research on the role of metabotropic glutamate receptors in schizophrenia etiopathology.
15
MASU, MASAYUKI, YOSHIAKI NAKAJIMA, KOKI MORIYOSHI, TAKAHIRO ISHII, CHIHIRO AKAZAWA, and SHIGETADA NAKANASHI. "Molecular Characterization of NMDA and Metabotropic Glutamate Receptors." Annals of the New York Academy of Sciences 707, no. 1 Molecular Bas (December 1993): 153–64. http://dx.doi.org/10.1111/j.1749-6632.1993.tb38050.x.
Full text
16
Lu, Lingling, Adam D. Hogan-Cann, Andrea K. Globa, Ping Lu, James I. Nagy, Shernaz X. Bamji, and Christopher M. Anderson. "Astrocytes drive cortical vasodilatory signaling by activating endothelial NMDA receptors." Journal of Cerebral Blood Flow & Metabolism 39, no. 3 (October 26, 2017): 481–96. http://dx.doi.org/10.1177/0271678x17734100.
Full textAbstract:
Astrocytes express neurotransmitter receptors that serve as sensors of synaptic activity and initiate signals leading to activity-dependent local vasodilation and increases in blood flow. We previously showed that arteriolar vasodilation produced by activation of cortical astrocytes is dependent on endothelial nitric oxide synthase (eNOS) and endogenous agonists of N-methyl-D-aspartate (NMDA) receptors. Here, we tested the hypothesis that these effects are mediated by NMDA receptors expressed by brain endothelial cells. Primary endothelial cultures expressed NMDA receptor subunits and produced nitric oxide in response to co-agonists, glutamate and D-serine. In cerebral cortex in situ, immunoelectron microscopy revealed that endothelial cells express the GluN1 NMDA receptor subunit at basolateral membrane surfaces in an orientation suitable for receiving intercellular messengers from brain cells. In cortical slices, activation of astrocytes by two-photon flash photolysis of a caged Ca2+ compound or application of a metabotropic glutamate receptor agonist caused endothelial NO generation and local vasodilation. These effects were mitigated by NMDA receptor antagonists and conditional gene silencing of endothelial GluN1, indicating at least partial dependence on endothelial NMDA receptors. Our observations identify a novel astrocyte-endothelial vasodilatory signaling axis that could contribute to endothelium-dependent vasodilation in brain functional hyperemia.
17
Evans, P. D., V. Reale, R. M. Merzon, and J. Villegas. "N-methyl-D-aspartate (NMDA) and non-NMDA (metabotropic) type glutamate receptors modulate the membrane potential of the Schwann cell of the squid giant nerve fibre." Journal of Experimental Biology 173, no. 1 (December 1, 1992): 229–49. http://dx.doi.org/10.1242/jeb.173.1.229.
Full textAbstract:
L-Glutamate application can produce three different responses in the membrane potential of the Schwann cell of the tropical squid, Sepioteuthis sepioidea, which appear to be mediated by three pharmacologically distinct classes of receptor. A class of non-NMDA-type receptors, with some similarities to metabotropic glutamate receptors, mediates the development of a rapid and long-lasting hyperpolarization. Two pharmacologically distinct classes of NMDA-type receptor are present. One mediates the development of a slow depolarization accompanied by a long-lasting change in responsiveness of the Schwann cell. The second produces rapid depolarizing responses during the period of this changed responsiveness. All three types of receptor can be activated by dipeptides containing excitatory amino acids.
18
Morley, Paul, Daniel L. Small, Christine L. Murray, Geoffrey A. Mealing, Michael O. Poulter, Jon P. Durkin, and Danica B. Stanimirovic. "Evidence that Functional Glutamate Receptors are not Expressed on Rat or Human Cerebromicrovascular Endothelial Cells." Journal of Cerebral Blood Flow & Metabolism 18, no. 4 (April 1998): 396–406. http://dx.doi.org/10.1097/00004647-199804000-00008.
Full textAbstract:
Excitatory amino acids can modify the tone of cerebral vessels and permeability of the blood-brain barrier (BBB) by acting directly on endothelial cells of cerebral vessels or indirectly by activating receptors expressed on other brain cells. In this study we examined whether rat or human cerebromicrovascular endothelial cells (CEC) express ionotropic and metabotropic glutamate receptors. Glutamate and the glutamate receptor agonists N-methyl-d-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA), and kainate failed to increase [Ca2+]i in either rat or human microvascular and capillary CEC but elicited robust responses in primary rat cortical neurons, as measured by fura-2 fluorescence. The absence of NMDA and AMPA receptors in rat and human CEC was further confirmed by the lack of immunocytochemical staining of cells by antibodies specific for the AMPA receptor subunits GluR1, GluR2/3, and GluR4 and the NMDA receptor subunits NR1, NR2A, and NR2B. We failed to detect mRNA expression of the AMPA receptor subunits GluR1 to GluR4 or the NMDA receptor subunits NR11XX, NR10XX, and NR2A to NR2C in both freshly isolated rat and human microvessels and cultured CEC using reverse transcriptase polymerase chain reaction (RT-PCR). Cultured rat CEC expressed mRNA for KA1 or KA2 and GluR5 subunits. Primary rat cortical neurons were found to express GluR1 to GluR3 and NR1, NR2A, and NR2B by both immunocytochemistry and RT-PCR and KA1, KA2, GluR5, GluR6, and GluR7 by RT-PCR. Moreover, the metabotropic glutamate receptor agonist 1-amino-cyclopentyl-1 S, 3 R-dicorboxylate (1 S,3 R-trans-ACPD), while eliciting both inositol trisphosphate and [Ca2+]i increases and inhibiting forskolin-stimulated cyclic AMP in cortical neurons, was unable to induce either of these responses in rat or human CEC. These results strongly suggest that both rat and human CEC do not express functional glutamate receptors. Therefore, excitatory amino acid-induced changes in the cerebral microvascular tone and BBB permeability must be affected indirectly, most likely by mediators released from the adjacent glutamate-responsive cells.
19
Kapsali, F., C. Tsopelas, I. Kamilaris, M. Dimitraka, and A. Sardis. "Glutamate and Depression." European Psychiatry 24, S1 (January 2009): 1. http://dx.doi.org/10.1016/s0924-9338(09)70883-1.
Full textAbstract:
Glutamate is the principal excitatory neurotransmitter in the cerebral cortex and it is implicated in the pathophysiology of depression and antidepressant activity.Aim:Aim of this study is to review recent studies and examine the physiology of glutamate and its receptors, pathophysiology of NMDA, effects of stress on glial cells and glutamate neurotransmission and explore the antidepressant properties of NMDA antagonists.Method:Review of recent pharmacological, imaging and genetic studies.Results:Increasing evidence supports a tight relationship between stress, the glutamatergic system and depression. Extracellular glutamate concentrations are increased in several brain regions including prefrontal cortex and hippocampus after exposure to stress. Interactions between glutamate and other neurotransmitters are discussed, as are possible mechanisms by which such altered receptor activity might result in the clinical expression of depression.A variety of NMDA antagonists, group I metabotropic glutamate receptor antagonists, as well as positive modulators of AMPA receptors, demonstrate efficacy in various preclinical modelsConclusions:It seems that a breakthrough in the therapy of depression will require going beyond monoamine-based theory of depression. Evidence indicates that the glutaminergic system might be a promising target fir novel antidepressant therapy.
20
Kullmann, Dimitri M., Ming-Yuan Min, Fredrik Asztely, and Dmitri A. Rusakov. "Extracellular glutamate diffusion determines the occupancy of glutamate receptors at CA1 synapses in the hippocampus." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 354, no. 1381 (February 28, 1999): 395–402. http://dx.doi.org/10.1098/rstb.1999.0392.
Full textAbstract:
Following exocytosis at excitatory synapses in the brain, glutamate binds to several subtypes of postsynaptic receptors. The degree of occupancy of AMPA and NMDA receptors at hippocampal synapses is, however, not known. One approach to estimate receptor occupancy is to examine quantal amplitude fluctuations of postsynaptic signals in hippocampal neurons studied in vitro . The results of such experiments suggest that NMDA receptors at CA1 synapses are activated not only by glutamate released from the immediately apposed presynaptic terminals, but also by glutamate spillover from neighbouring terminals. Numerical simulations point to the extracellular diffusion coefficient as a critical parameter that determines the extent of activation of receptors positioned at different distances from the release site. We have shown that raising the viscosity of the extracellular medium can modulate the diffusion coefficient, providing an experimental tool to investigate the role of diffusion in activation of synaptic and extrasynaptic receptors. Whether intersynaptic cross–talk mediated by NMDA receptors occurs in vivo remains to be determined. The theoretical and experimental approaches described here also promise to shed light on the roles of metabotropic and kainate receptors, which often occur in an extrasynaptic distribution, and are therefore positioned to sense glutamate escaping from the synaptic cleft.
21
Karakossian, Movses H., and Thomas S. Otis. "Excitation of Cerebellar Interneurons by Group I Metabotropic Glutamate Receptors." Journal of Neurophysiology 92, no. 3 (September 2004): 1558–65. http://dx.doi.org/10.1152/jn.00300.2004.
Full textAbstract:
Cerebellar basket and stellate neurons (BSNs) provide feed-forward inhibition to Purkinje neurons (PNs) and thereby play a principal role in determining the output of the cerebellar cortex. During low-frequency transmission, glutamate released at parallel fiber synapses excites BSNs by binding to AMPA receptors; high-frequency transmission also recruits N-methyl-d-aspartate (NMDA) receptors. We find that, in addition to these ligand-gated receptors, a G-protein–coupled glutamate receptor subtype participates in exciting BSNs. Stimulation of metabotropic glutamate receptor 1α (mGluR1α) with the mGluR agonist ( RS)-3,5-dihydroxyphenylglycine (DHPG) leads to an increase in spontaneous firing of BSNs and indirectly to an increase in the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded in PNs. Under conditions in which ligand-gated glutamate receptors are blocked, parallel fiber stimulation generates a slow excitatory postsynaptic current (EPSC) in BSNs that is inhibited by mGluR1α-selective antagonists. This slow EPSC is capable of increasing BSN spiking and indirectly increasing sIPSCs frequency in PNs. Our findings reinforce the idea that distinct subtypes of glutamate receptors are activated in response to different patterns of activity at excitatory synapses. The results also raise the possibility that mGluR1α-dependent forms of synaptic plasticity may occur at excitatory inputs to BSNs.
22
Salt, T. E. "Glutamate receptor functions in sensory relay in the thalamus." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 357, no. 1428 (December 29, 2002): 1759–66. http://dx.doi.org/10.1098/rstb.2002.1165.
Full textAbstract:
It is known that glutamate is a major excitatory transmitter of sensory and cortical afferents to the thalamus. These actions are mediated via several distinct receptors with postsynaptic excitatory effects predominantly mediated by ionotropic receptors of the α–amino–3–hydroxy–5–methyl–4–isoxazolepropionate (AMPA) and N –methyl–D–aspartate varieties (NMDA). However, there are also other kinds of glutamate receptor present in the thalamus, notably the metabotropic and kainate types, and these may have more complex or subtle roles in sensory transmission. This paper describes recent electrophysiological experiments done in vitro and in vivo which aim to determine how the metabotropic and kainate receptor types can influence transmission through the sensory thalamic relay. A particular focus will be how such mechanisms might operate under physiological conditions.
23
Martin, Gilles, Zhiguo Nie, and George R. Siggins. "Metabotropic Glutamate Receptors Regulate N-Methyl-d-Aspartate–Mediated Synaptic Transmission in Nucleus Accumbens." Journal of Neurophysiology 78, no. 6 (December 1, 1997): 3028–38. http://dx.doi.org/10.1152/jn.1997.78.6.3028.
Full textAbstract:
Martin, Gilles, Zhiguo Nie, and George R. Siggins. Metabotropic glutamate receptors regulate N-methyl-d-aspartate–mediated synaptic transmission in nucleus accumbens. J. Neurophysiol. 78: 3028–3038, 1997. We recorded intracellularly from core nucleus accumbens (NAcc) neurons in brain slices to study the regulation by metabotropic glutamate receptors (mGluRs) of pharmacologically isolated N-methyl-d-aspartate–mediated excitatory postsynaptic currents (NMDA-EPSCs). Monosynaptic NMDA-EPSCs, evoked by local stimulation, were isolated by superfusion of the non-NMDA and γ-aminobutyric acid-A (GABAA) receptor antagonists, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 μM) and bicuculline (15 μM), respectively. Trans-1-aminocyclopentane-1,3-decarboxylic acid ( trans-ACPD; 50 μM), a nonspecific group 1 and 2 mGluR agonist, had no effect on resting membrane potential (RMP) or input resistance of NAcc neurons. However, it consistently decreased NMDA-EPSC areas (time integrals) dose dependently (1–100 μM; EC50 = 8 μM) and reversibly. The specific group 1 mGluR agonists quisqualate (1–4 μM) and (RS)-3,5-dihydroxyphenylglycine (DHPG; 100 μM) did not mimic the trans-ACPD effect on NMDA-EPSCs, nor did exposure of the slice to the group 1 mGluR antagonist l(+)-2-amino-3-phosphonopropionic acid (l-AP3, 0.4 mM) inhibit the trans-ACPD effect. The putative mGluR1 and mGluR2 antagonist (+)-α-methyl-4-carboxyphenylglycine (MCPG) at 0.5 mM failed to antagonize trans-ACPD effects but at 1 mM blocked them. Both the group 2 mGluR agonist (2S,3S,4S)-α-(carboxycyclopropyl)-glycine (l-CCG-I, 2 μM) and the group 3 mGluR specific agonist l(+)-2-amino-4-phosphonobutyric acid (l-AP4, 20 μM) attenuated NMDA-EPSC areas; the effect of l-AP4 was blocked by the group 3 antagonist (S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP4; 0.5 mM). Exogenously applied NMDA, in the presence of tetrodotoxin to prevent presynaptic effects, induced inward currents that were decreased by 20 μM l-AP4 but not by 10 μM trans-ACPD. These findings suggest that NMDA receptor-mediated neurotransmission in NAcc is under dual inhibitory regulation by group 2 and 3 metabotropic receptor subtypes: l-AP4–sensitive receptors located postsynaptically and those sensitive to trans-ACPD located presynaptically.
24
Severina, Hanna I., Victoriya A. Georgiyants, Sergiy M. Kovalenko, Natalia V. Avdeeva, Artem I. Yarcev, and Svetlana N. Prohoda. "Molecular docking studies of N-substituted 4-methoxy-6-oxo-1-aryl-pyridazine-3-carboxamide derivatives as potential modulators of glutamate receptors." Research Results in Pharmacology 6, no. 1 (March 30, 2020): 69–82. http://dx.doi.org/10.3897/rrpharmacology.6.52026.
Full textAbstract:
Introduction: The virtual target-oriented screening is a necessary stage of modern drug-design. In the present study, the affinity of pyridazine derivatives for the most promising antiparkinsonian biotargets – I–III groups of metabotropic and ionotropic NMDA-glutamate receptors – was evaluated. Materials and methods: Docking of the studied ligands to the active sites of biotargets – mGluR5, mGluR3, mGluR8, NMDA GluN2B – was performed using AutoDockVina. Base of the preparation of ligands and proteins – AutoDockTools-1.5.6. A Discovery Studio Visualizer 2017/R2 was used to visualize the interpretation of the results. Results and discussion: A high degree of the affinity is predicted for group III of the metabotropic mGlu8 receptors – binding energy from -5.0 to -8.7 kcal/mol, compared to -6.1 kcal/mol of that of the reference drug (L-AP4), as well as for the ionotropic NMDA GluN2B receptors –binding energy from -8.7 to -11.6 kcal/mol, compared to -11.3 kcal/mol of that of ifenprodil. Conclusion: The prospects of the searching for glutamate receptor modulators in a number of n-substituted 4-methoxy-6-oxo-1-aryl-pyridazine-3-carboxamide derivatives are proved. Some aspects of the structure-affinity relationship are discussed.
25
Schapansky, Jason, Marc Morissette, Gary Odero, Benedict Albensi, and Gordon Glazner. "Neuregulin β1 enhances peak glutamate-induced intracellular calcium levels through endoplasmic reticulum calcium release in cultured hippocampal neuronsThis article is one of a selection of papers published in a special issue celebrating the 125th anniversary of the Faculty of Medicine at the University of Manitoba." Canadian Journal of Physiology and Pharmacology 87, no. 10 (October 2009): 883–91. http://dx.doi.org/10.1139/y09-082.
Full textAbstract:
Modulation of intracellular free calcium levels is the primary second messenger system of the neuronal glutamatergic system, playing a role in regulation of all major cellular processes. The protein neuregulin (NRG) β1 acts as an extracellular signaling ligand in neurons, rapidly regulating currents through ionotropic glutamate receptors. The effect NRG may have on glutamate-induced changes in intracellular free calcium concentrations has not been examined, however. In this study, cultured embryonic rat hippocampal neurons were treated with NRGβ1 to determine a possible effect on glutamate-induced intracellular calcium levels. Long-term (24 h), but not short-term (1 h), incubation with NRGβ1 resulted in a significantly greater glutamate-mediated acute peak elevation of intracellular calcium levels than occurred in vehicle-treated neurons. Long-term NRGβ1 incubation significantly enhanced calcium increase induced by specific stimulation of metabotropic glutamate receptors, but did not significantly alter the N-methyl d-aspartate (NMDA)- or KCl-induced calcium increase and paradoxically decreased the effect of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) treatment on intracellular calcium. Metabotropic glutamate receptors cause increased intracellular free calcium via release of calcium from intracellular stores; thus this system was examined in more detail. NRGβ1 treatment significantly (greater than 2-fold) enhanced calcium release from endoplasmic reticulum stores after stimulation of ryanodine receptors with caffeine, but did not significantly increase calcium release from endoplasmic reticulum mediated by inositol trisphosphate (IP3) receptors. In addition, ryanodine receptor inhibition with ruthenium red prevented the glutamate-induced increase in intracellular calcium levels in NRGβ1-treated neurons. These data show that long-term NRGβ1 treatment can enhance glutamate-induced peak intracellular calcium levels through metabotropic glutamate receptor activation by increasing endoplasmic reticulum calcium release through ryanodine receptors.
26
Kim, Jong-Hoon, János Marton, Simon Mensah Ametamey, and Paul Cumming. "A Review of Molecular Imaging of Glutamate Receptors." Molecules 25, no. 20 (October 16, 2020): 4749. http://dx.doi.org/10.3390/molecules25204749.
Full textAbstract:
Molecular imaging with positron emission tomography (PET) and single photon emission computed tomography (SPECT) is a well-established and important in vivo technique to evaluate fundamental biological processes and unravel the role of neurotransmitter receptors in various neuropsychiatric disorders. Specific ligands are available for PET/SPECT studies of dopamine, serotonin, and opiate receptors, but corresponding development of radiotracers for receptors of glutamate, the main excitatory neurotransmitter in mammalian brain, has lagged behind. This state of affairs has persisted despite the central importance of glutamate neurotransmission in brain physiology and in disorders such as stroke, epilepsy, schizophrenia, and neurodegenerative diseases. Recent years have seen extensive efforts to develop useful ligands for molecular imaging of subtypes of the ionotropic (N-methyl-D-aspartate (NMDA), kainate, and AMPA/quisqualate receptors) and metabotropic glutamate receptors (types I, II, and III mGluRs). We now review the state of development of radioligands for glutamate receptor imaging, placing main emphasis on the suitability of available ligands for reliable in vivo applications. We give a brief account of the radiosynthetic approach for selected molecules. In general, with the exception of ligands for the GluN2B subunit of NMDA receptors, there has been little success in developing radiotracers for imaging ionotropic glutamate receptors; failure of ligands for the PCP/MK801 binding site in vivo doubtless relates their dependence on the open, unblocked state of the ion channel. Many AMPA and kainite receptor ligands with good binding properties in vitro have failed to give measurable specific binding in the living brain. This may reflect the challenge of developing brain-penetrating ligands for amino acid receptors, compounded by conformational differences in vivo. The situation is better with respect to mGluR imaging, particularly for the mGluR5 subtype. Several successful PET ligands serve for investigations of mGluRs in conditions such as schizophrenia, depression, substance abuse and aging. Considering the centrality and diversity of glutamatergic signaling in brain function, we have relatively few selective and sensitive tools for molecular imaging of ionotropic and metabotropic glutamate receptors. Further radiopharmaceutical research targeting specific subtypes and subunits of the glutamate receptors may yet open up new investigational vistas with broad applications in basic and clinical research.
27
Hammond-Weinberger, Dena R., Yunxin Wang, Alex Glavis-Bloom, and Nicholas C. Spitzer. "Mechanism for neurotransmitter-receptor matching." Proceedings of the National Academy of Sciences 117, no. 8 (February 10, 2020): 4368–74. http://dx.doi.org/10.1073/pnas.1916600117.
Full textAbstract:
Synaptic communication requires the expression of functional postsynaptic receptors that match the presynaptically released neurotransmitter. The ability of neurons to switch the transmitter they release is increasingly well documented, and these switches require changes in the postsynaptic receptor population. Although the activity-dependent molecular mechanism of neurotransmitter switching is increasingly well understood, the basis of specification of postsynaptic neurotransmitter receptors matching the newly expressed transmitter is unknown. Using a functional assay, we show that sustained application of glutamate to embryonic vertebrate skeletal muscle cells cultured before innervation is necessary and sufficient to up-regulate ionotropic glutamate receptors from a pool of different receptors expressed at low levels. Up-regulation of these ionotropic receptors is independent of signaling by metabotropic glutamate receptors. Both imaging of glutamate-induced calcium elevations and Western blots reveal ionotropic glutamate receptor expression prior to immunocytochemical detection. Sustained application of glutamate to skeletal myotomes in vivo is necessary and sufficient for up-regulation of membrane expression of the GluN1 NMDA receptor subunit. Pharmacological antagonists and morpholinos implicate p38 and Jun kinases and MEF2C in the signal cascade leading to ionotropic glutamate receptor expression. The results suggest a mechanism by which neuronal release of transmitter up-regulates postsynaptic expression of appropriate transmitter receptors following neurotransmitter switching and may contribute to the proper expression of receptors at the time of initial innervation.
28
Sun, Dandan, and Sangita G. Murali. "Stimulation of Na+-K+-2Cl−cotransporter in neuronal cells by excitatory neurotransmitter glutamate." American Journal of Physiology-Cell Physiology 275, no. 3 (September 1, 1998): C772—C779. http://dx.doi.org/10.1152/ajpcell.1998.275.3.c772.
Full textAbstract:
Na+-K+-2Cl−cotransporters are important in renal salt reabsorption and in salt secretion by epithelia. They are also essential in maintenance and regulation of ion gradients and cell volume in both epithelial and nonepithelial cells. Expression of Na+-K+-2Cl−cotransporters in brain tissues is high; however, little is known about their function and regulation in neurons. In this study, we examined regulation of the Na+-K+-2Cl−cotransporter by the excitatory neurotransmitter glutamate. The cotransporter activity in human neuroblastoma SH-SY5Y cells was assessed by bumetanide-sensitive K+ influx, and protein expression was evaluated by Western blot analysis. Glutamate was found to induce a dose- and time-dependent stimulation of Na+-K+-2Cl−cotransporter activity in SH-SY5Y cells. Moreover, both the glutamate ionotropic receptor agonist N-methyl-d-aspartic acid (NMDA) and the metabotropic receptor agonist (±)-1-aminocyclopentane- trans-1,3-dicarboxylic acid ( trans-ACPD) significantly stimulated the cotransport activity in these cells. NMDA-mediated stimulation of the Na+-K+-2Cl−cotransporter was abolished by the selective NMDA-receptor antagonist (+)-MK-801 hydrogen maleate. trans-ACPD-mediated effect on the cotransporter was blocked by the metabotropic receptor antagonist (+)-α-methyl-(4-carboxyphenyl)glycine. The results demonstrate that Na+-K+-2Cl−cotransporters in neurons are regulated by activation of both ionotropic and metabotropic glutamate receptors.
29
Rao, Yan, and Nigel W. Daw. "Layer Variations of Long-Term Depression in Rat Visual Cortex." Journal of Neurophysiology 92, no. 5 (November 2004): 2652–58. http://dx.doi.org/10.1152/jn.00298.2004.
Full textAbstract:
In vitro long-term depression (LTD) is thought to be a model for the loss of cortical responsiveness to an eye deprived of vision during the critical period. Using whole cell recording, the present study investigates the mechanisms of LTD in vitro across layers in developing rat visual cortex. LTD was induced in layers II/III, V, and VI but not layer IV with 10-min 1-Hz stimulation paired with postsynaptic depolarization. LTD in layers II/III and V could be blocked by the N-methyl-d-aspartate (NMDA) receptor antagonist d-aminophosphonovaleric acid (d-AP5) but not by 100 μM (2S)-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495), a metabotropic glutamate receptor inhibitor. In contrast, LTD in layer VI was blocked by 100 μM LY341495 and (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) but not d-AP5 and partially blocked by application of guanosine 5′- O-(2-thiodiphosphate) thilothium salt (GDP-β-S) in patch pipette, suggesting an involvement of postsynaptic group I metabotropic glutamate receptors (mGluRs). These results indicate that LTD in developing rat visual cortex varies with layer: LTD was absent in layer IV, suggesting a unique plasticity mechanism at geniculocortical synapses; LTD in layers II/III and V depends on NMDA receptors but not mGluRs, and LTD in layer VI requires mGluRs but not NMDA receptors.
30
Guntupalli, Sumasri, Jocelyn Widagdo, and Victor Anggono. "Amyloid-β-Induced Dysregulation of AMPA Receptor Trafficking." Neural Plasticity 2016 (2016): 1–12. http://dx.doi.org/10.1155/2016/3204519.
Full textAbstract:
Evidence from neuropathological, genetic, animal model, and biochemical studies has indicated that the accumulation of amyloid-beta (Aβ) is associated with, and probably induces, profound neuronal changes in brain regions critical for memory and cognition in the development of Alzheimer’s disease (AD). There is considerable evidence that synapses are particularly vulnerable to AD, establishing synaptic dysfunction as one of the earliest events in pathogenesis, prior to neuronal loss. It is clear that excessive Aβlevels can disrupt excitatory synaptic transmission and plasticity, mainly due to dysregulation of the AMPA and NMDA glutamate receptors in the brain. Importantly, AMPA receptors are the principal glutamate receptors that mediate fast excitatory neurotransmission. This is essential for synaptic plasticity, a cellular correlate of learning and memory, which are the cognitive functions that are most disrupted in AD. Here we review recent advances in the field and provide insights into the molecular mechanisms that underlie Aβ-induced dysfunction of AMPA receptor trafficking. This review focuses primarily on NMDA receptor- and metabotropic glutamate receptor-mediated signaling. In particular, we highlight several mechanisms that underlie synaptic long-term depression as common signaling pathways that are hijacked by the neurotoxic effects of Aβ.
31
Hedberg, Thomas G., Ellen F. Sperber, Jana Velíšková, and Solomon L. Moshé. "Laminar and Temporal Heterogeneity of NMDA/Metabotropic Glutamate Receptor Binding in Posterior Cingulate Cortex." Journal of Neurophysiology 84, no. 4 (October 1, 2000): 1881–87. http://dx.doi.org/10.1152/jn.2000.84.4.1881.
Full textAbstract:
Both N-methyl-d-aspartate (NMDA) and quisqualate/AMPA-insensitive metabotropic glutamate (mGlu) receptors mediate plasticity induction in neocortex, but their interlaminar distribution in cortical microcircuits is largely unknown. We used (+)3H-MK801 and3H-glutamate binding plus saturating concentrations of NMDA, AMPA, and quisqualate to autoradiographically map NMDA and mGlu receptor sites by lamina in posterior cingulate cortex in adult male rats. Specific binding at NMDA receptor sites in laminae II/III and VI was significantly reduced in comparison to other laminae. Brains prepared from rats killed during dark phase of a 12h/12h light/dark cycle showed a mean 129% increase in overall (+)3H-MK801 binding versus light phase brains but retained reduced binding densities in laminae II/III and VI. In contrast to NMDA findings, specific binding at mGlu sites was consistently elevated during light phase in both laminae II/III and VI. Specific 3H-glutamate binding in dark-phase brains showed an overall 147% increase versus light phase binding but did not retain significant interlaminar heterogeneity. Interpreted in accordance with our physiologically derived models of hippocampo-cortical microcircuitry, these results suggest that spatial and temporal variations in glutamate receptor distribution may play an important role in intracingulate neural processing of afferent input from hippocampus.
32
Tyszkiewicz, Joanna P., and Zhen Yan. "β-Amyloid Peptides Impair PKC-Dependent Functions of Metabotropic Glutamate Receptors in Prefrontal Cortical Neurons." Journal of Neurophysiology 93, no. 6 (June 2005): 3102–11. http://dx.doi.org/10.1152/jn.00939.2004.
Full textAbstract:
The metabotropic glutamate receptors (mGluRs) have been implicated in cognition, memory, and some neurodegenerative disorders, including the Alzheimer's disease (AD). To understand how the dysfunction of mGluRs contributes to the pathophysiology of AD, we examined the β-amyloid peptide (Aβ)-induced alterations in the physiological functions of mGluRs in prefrontal cortical pyramidal neurons. Two potential targets of mGluR signaling involved in cognition, the GABAergic system and the N-methyl-d-aspartate (NMDA) receptor, were examined. Activation of group I mGluRs with (S)-3,5-dihydroxyphenylglycine (DHPG) significantly increased the spontaneous inhibitory postsynaptic current (sIPSC) amplitude, and this effect was protein kinase C (PKC) sensitive. Treatment with Aβ abolished the DHPG-induced enhancement of sIPSC amplitude. On the other hand, activation of group II mGluRs with (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC) significantly increased the NMDA receptor (NMDAR)-mediated currents via a PKC-dependent mechanism, and Aβ treatment also diminished the APDC-induced potentiation of NMDAR currents. In Aβ-treated slices, both DHPG and APDC failed to activate PKC. These results indicate that the mGluR regulation of GABA transmission and NMDAR currents is impaired by Aβ treatment probably due to the Aβ-mediated interference of mGluR activation of PKC. This study provides a framework within which the role of mGluRs in normal cognitive functions and AD can be better understood.
33
Fellin, Tommaso, Marcello D'Ascenzo, and Philip G. Haydon. "Astrocytes Control Neuronal Excitability in the Nucleus Accumbens." Scientific World JOURNAL 7 (2007): 89–97. http://dx.doi.org/10.1100/tsw.2007.195.
Full textAbstract:
Though accumulating evidence shows that the metabotropic glutamate receptor 5 (mGluR5) mediates some of the actions of extracellular glutamate after cocaine use, the cellular events underlying this action are poorly understood. In this review, we will discuss recent results showing that mGluR5 receptors are key regulators of astrocyte activity. Synaptic release of glutamate activates mGluR5 expressed in perisynaptic astrocytes and generates intense Ca2+signaling in these cells. Ca2+oscillations, in turn, trigger the release from astrocytes of the gliotransmitter glutamate, which modulates neuronal excitability by activating NMDA receptors. By integrating these results with the most recent evidence demonstrating the importance of astrocytes in the regulation of neuronal excitability, we propose that astrocytes are involved in mediating some of the mGluR5-dependent drug-induced behaviors.
34
O'Neill, Nathanael, Catherine McLaughlin, Noboru Komiyama, and Sergiy Sylantyev. "Biphasic Modulation of NMDA Receptor Function by Metabotropic Glutamate Receptors." Journal of Neuroscience 38, no. 46 (October 3, 2018): 9840–55. http://dx.doi.org/10.1523/jneurosci.1000-18.2018.
Full text
35
DiMicco, J., and A. J. Monroe. "Stimulation of metabotropic glutamate receptors in the dorsomedial hypothalamus elevates heart rate in rats." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 270, no. 5 (May 1, 1996): R1115—R1121. http://dx.doi.org/10.1152/ajpregu.1996.270.5.r1115.
Full textAbstract:
This study examined the potential role of metabotropic glutamate receptors (mGluRs) in the dorsomedial hypothalamus (DMH) by assessing the cardiovascular effects of microinjecting the agonist trans-1-aminocyclopentane-1, 3- dicarboxylate (tACPD) into this region in urethan-anesthetized rats. Dose-related tachycardia was observed after unilateral microinjection of 1S 3R-tACPD (10-200 pmol/50nl) but not after injection of 1R, 3S-tACPD, which has been reported to have little or no activity at mGluRs. Microinjection of dihydroxyphenylglycine, an agonist at mGluRs linked to phosphoinositide hydrolysis, resulted in increases in heart rate that correlated closely in magnitude to those seen after injection of the same dose of 1S, 3R-tACPD. Coinjection of the N-methyl-D-aspartate (NMDA) receptor antagonist DL-2- amino-5-phosphonopentanoic acid, given at doses shown to elicit selective blockade of NMDA ionotropic glutamate receptors, reduced the increase in heart rate evoked by 100 pmol 1S, 3R-tACPD alone. Thus the DMH contains functional mGluRs, and stimulation of these receptors activates the same sympathoexcitatory mechanism characterized previously to provoke dose-related tachycardia.
36
Liu, Yan, Shan Wang, Jun Kan, Jingzhi Zhang, Lisa Zhou, Yuli Huang, and Yunlong Zhang. "Chinese Herbal Medicine Interventions in Neurological Disorder Therapeutics by Regulating Glutamate Signaling." Current Neuropharmacology 18, no. 4 (March 20, 2020): 260–76. http://dx.doi.org/10.2174/1570159x17666191101125530.
Full textAbstract:
Glutamate is the major excitatory neurotransmitter in the central nervous system, and its signaling is critical for excitatory synaptic transmission. The well-established glutamate system involves glutamate synthesis, presynaptic glutamate release, glutamate actions on the ionotropic glutamate receptors (NMDA, AMPA, and kainate receptors) and metabotropic glutamate receptors, and glutamate uptake by glutamate transporters. When the glutamate system becomes dysfunctional, it contributes to the pathogenesis of neurodegenerative and neuropsychiatric diseases such as Alzheimer's disease, Parkinson's disease, depression, epilepsy, and ischemic stroke. In this review, based on regulating glutamate signaling, we summarize the effects and underlying mechanisms of natural constituents from Chinese herbal medicines on neurological disorders. Natural constituents from Chinese herbal medicine can prevent the glutamate-mediated excitotoxicity via suppressing presynaptic glutamate release, decreasing ionotropic and metabotropic glutamate receptors expression in the excitatory synapse, and promoting astroglial glutamate transporter expression to increase glutamate clearance from the synaptic cleft. However, some natural constituents from Chinese herbal medicine have the ability to restore the collapse of excitatory synapses by promoting presynaptic glutamate release and increasing ionotropic and metabotropic glutamate receptors expression. These regulatory processes involve various signaling pathways, which lead to different mechanistic routes of protection against neurological disorders. Hence, our review addresses the underlying mechanisms of natural constituents from Chinese herbal medicines that regulate glutamate systems and serve as promising agents for the treatment of the above-mentioned neurological disorders.
37
KOMANDIROV, M. A., E. A. KNYAZEVA, Y. P. FEDORENKO, M. V. RUDKOVSKII, E. V. BEREZHNAYA, V. D. KOVALEVA, and A. B. UZDENSKY. "CHEMICAL MODULATION OF PHOTODYNAMIC INJURY OF GLIAL CELLS." Journal of Innovative Optical Health Sciences 04, no. 04 (October 2011): 429–35. http://dx.doi.org/10.1142/s1793545811001605.
Full textAbstract:
Photodynamic therapy based on photogeneration of cytotoxic singlet oxygen and following oxidative stress is currently used in neuro-oncology for destruction of brain tumors. However, along with a tumor, it damages healthy neurons and glial cells. We studied the involvement of the glutamate-related signaling pathway in photodynamic damage to normal glial cells in the crayfish stretch receptor. This model object consists of a single neuron surrounded by glial cells. It was photosensitized with alumophthalocyanine Photosens and irradiated by the diode laser (670 nm). Application of enzyme inhibitors and ion channels modulators showed that exogenous L-glutamate decreased photoinduced apoptosis of crayfish glial cells. The natural neuroglial mediator N-acetylaspartylglutamate, which releases glutamate after splitting by glutamate carboxypeptidase II, also inhibited photoinduced apoptosis. Inhibition of glutamate carboxypeptidase II, oppositely, enhanced glial apoptosis. This confirmed the antiapoptotic activity of glutamate. Glutamate agonist NMDA or inhibitor of NMDA receptors MK801 did not influence photodynamic death of glial cells, i.e., these receptors did not participate in glial apoptosis. Inhibition of metabotropic glutamate receptors mGluRI with AP-3 reduced PDT-induced apoptosis of glial cells. Thus, chemical modifiers of various signaling processes can modulate photoinduced necrosis or apoptosis of glial cells and thus modify efficiency of photodynamic therapy.
38
Spampinato, Simona Federica, Sara Merlo, Gemma Molinaro, Giuseppe Battaglia, Valeria Bruno, Ferdinando Nicoletti, and Maria Angela Sortino. "Dual Effect of 17β-Estradiol on NMDA-Induced Neuronal Death: Involvement of Metabotropic Glutamate Receptor 1." Endocrinology 153, no. 12 (December 1, 2012): 5940–48. http://dx.doi.org/10.1210/en.2012-1799.
Full textAbstract:
Abstract Pretreatment with 10 nm 17β-estradiol (17βE2) or 100 μm of the metabotropic glutamate 1 receptor (mGlu1R) agonist, dihydroxyphenylglycine (DHPG), protected neurons against N-methyl-d-aspartate (NMDA) toxicity. This effect was sensitive to blockade of both estrogen receptors and mGlu1R by their respective antagonists. In contrast, 17βE2 and/or DHPG, added after a low-concentration NMDA pulse (45 μm), produced an opposite effect, i.e. an exacerbation of NMDA toxicity. Again this effect was prevented by both receptor antagonists. In support of an interaction of estrogen receptors and mGlu1R in mediating a neurotoxic response, exacerbation of NMDA toxicity by 17βE2 disappeared when cultures were treated with DHPG prior to NMDA challenge, and conversely, potentiation of NMDA-induced cell death by DHPG was prevented by pretreatment with 17βE2. Addition of calpain III inhibitor (10 μm), 2 h before NMDA, prevented the increased damage induced by the two agonists, an affect that can be secondary to cleavage of mGlu1R by calpain. Accordingly, NMDA stimulation reduced expression of the full-length (140 kDa) mGluR1, an effect partially reversed by calpain inhibitor. Finally, in the presence of NMDA, the ability of 17βE2 to stimulate phosphorylation of AKT and ERK was impaired. Pretreatment with calpain inhibitor prevented the reduction of phosphorylated ERK but had no significant effect on phosphorylated AKT. Accordingly, the inhibition of ERK signaling by U0126 (1 μm) counteracted the effect of calpain inhibition on 17βE2-induced exacerbation of NMDA toxicity. The present data confirm the dual role of estrogens in neurotoxicity/neuroprotection and highlight the role of the timing of exposure to estrogens.
39
Haak, Laurel L. "Metabotropic Glutamate Receptor Modulation of Glutamate Responses in the Suprachiasmatic Nucleus." Journal of Neurophysiology 81, no. 3 (March 1, 1999): 1308–17. http://dx.doi.org/10.1152/jn.1999.81.3.1308.
Full textAbstract:
Metabotropic glutamate receptor modulation of glutamate responses in the suprachiasmatic nucleus. Glutamate is the primary excitatory transmitter in the suprachiasmatic nucleus (SCN). Ionotropic glutamate receptors (iGluRs) mediate transduction of light information from the retina to the SCN, an important circadian clock phase shifting pathway. Metabotropic glutamate receptors (mGluRs) may play a significant modulatory role. mGluR modulation of SCN responses to glutamate was investigated with fura-2 calcium imaging in SCN explant cultures. SCN neurons showed reproducible calcium responses to glutamate, kainate, and N-methyl-d-aspartate (NMDA). Although the type I/II mGluR agonists L-CCG-I and t-ACPD did not evoke calcium responses, they did inhibit kainate- and NMDA-evoked calcium rises. This interaction was insensitive to pertussis toxin. Protein kinase A (PKA) activation by 8-bromo-cAMP significantly reduced iGluR inhibition by mGluR agonists. The inhibitory effect of mGluRs was enhanced by activating protein kinase C (PKC) and significantly reduced in the presence of the PKC inhibitor H7. Previous reports show that L-type calcium channels can be modulated by PKC and PKA. In SCN cells, about one-half of the calcium rise evoked by kainate or NMDA was blocked by the L-type calcium channel antagonist nimodipine. Calcium rises evoked by K+ were used to test whether mGluR inhibition of iGluR calcium rises involved calcium channel modulation. These calcium rises were primarily attributable to activation of voltage-activated calcium channels. PKC activation inhibited K+-evoked calcium rises, but PKC inhibition did not affect L-CCG-I inhibition of these rises. In contrast, 8Br-cAMP had no effect alone but blocked L-CCG-I inhibition. Taken together, these results suggest that activation of mGluRs, likely type II, modulates glutamate-evoked calcium responses in SCN neurons. mGluR inhibition of iGluR calcium rises can be differentially influenced by PKC or PKA activation. Regulation of glutamate-mediated calcium influx could occur at L-type calcium channels, K+ channels, or at GluRs. It is proposed that mGluRs may be important regulators of glutamate responsivity in the circadian system.
40
Blue, Mary E., Lee J. Martin, Elizabeth M. Brennan, and Michael V. Johnston. "Ontogeny of non-NMDA glutamate receptors in rat barrel field cortex: I. metabotropic receptors." Journal of Comparative Neurology 386, no. 1 (September 15, 1997): 16–28. http://dx.doi.org/10.1002/(sici)1096-9861(19970915)386:1<16::aid-cne4>3.0.co;2-g.
Full text
41
Kuramoto, Takashi, Toshiro Maihara, Masayuki Masu, Shigetada Nakanishi, and Tadao Serikawa. "Gene Mapping of NMDA Receptors and Metabotropic Glutamate Receptors in the Rat (Rattus norvegicus)." Genomics 19, no. 2 (January 1994): 358–61. http://dx.doi.org/10.1006/geno.1994.1069.
Full text
42
Savolainen, Kai M., Pirkko Tervo, Jarkko Loikkanen, and Jonne Naarala. "Cholinergic and Glutaminergic Excitation of Neuronal Cells." Alternatives to Laboratory Animals 24, no. 3 (June 1996): 387–92. http://dx.doi.org/10.1177/026119299602400312.
Full textAbstract:
Excessive cholinergic or glutaminergic brain stimulation may result in seizures, excitotoxicity and neuronal damage. Cholinergic neuronal excitation is mediated via muscarinic receptors which couple with GTP-binding proteins (G–proteins), activate phospholipase C, and produce the inositol lipid second messengers, inositol-1,4,5,-trisphosphate (InsP3) and diacyl-glycerol (DG). InsP3 facilitates intracellular Ca2+ metabolism and DG activates protein kinase C (PKC). Glutaminergic neuronal stimulation is mediated through ionotropic N-methyl-D-aspartate (NMDA) receptors, which increase Ca2+ influx, and kainate α-amino-3-hydroxy-5-methyl-4-isoxalolproprionic acid receptors, which mainly regulate Na+ fluxes. Glutaminergic metabotropic receptors are also coupled to a G-protein, and their stimulation activates neurons through increased production of InsP3 and DG. A salient feature in glutamate-induced excitotoxicity is the induction of an oxidative burst, subsequent oxidative stress, and damage to the neurons. The glutamate-induced oxidative burst can be amplified by lead, a direct activator of PKC, and the oxidative burst can be blocked by a PKC inhibitor, suggesting an important role for PKC. Carbachol also induces an oxidative burst in neuronal cells and this is associated with elevations of free intracellular calcium. The ability of an NMDA receptor antagonist, AP-5, to block carbachol-induced elevations of free intracellular calcium, suggests that activation of muscarinic receptors is associated with a simultaneous glutamate receptor activation. Thus, cross-talk between cholinergic muscarinic and glutaminergic receptors may be an important contributing factor in cholinergic and glutaminergic excitotoxicity.
43
Parfenova, Helena, Alex Fedinec, and Charles W. Leffler. "Ionotropic Glutamate Receptors in Cerebral Microvascular Endothelium are Functionally Linked to Heme Oxygenase." Journal of Cerebral Blood Flow & Metabolism 23, no. 2 (February 2003): 190–97. http://dx.doi.org/10.1097/01.wcb.000004823561824.c4.
Full textAbstract:
Vasodilator effects of glutamate in the cerebral circulation are, in part, mediated by carbon monoxide (CO), which is formed from heme via the heme oxygenase (HO) pathway. The hypothesis addressed was that glutamate receptors (GluRs) in cerebral microvascular endothelium are functionally linked to HO. Using a radioligand binding and immunoblotting, GluRs were characterized in cerebral microvascular endothelial cells (CMVEC) from newborn pigs. High-affinity (80 nmol/L) reversible binding of [H]Glutamate ([3H]Glu) was detected in CMVEC membranes. The N-methyl-D-aspartate (NMDA) receptor ligands—NMDA, quinolinic acid, (±)1-aminocyclopentane- cis-1,3-dicarboxylic acid ( cis-ACPD), AP5, 4C3HPG, and CPP—and the (RS)-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate receptor ligands—AMPA, kainic acid, quisqualic acid, DNQX, and CNQX—displaced 20% to 30% of bound [3H]Glu in CMVEC membranes. Metabotropic GluRs antagonists (4CPG, PHCC, and CPPG) did not displace bound [3H]Glu. L-Aspartate, an agonist of GluRs and glutamate transporters, displaced 80% or more of bound [3H]Glu. Ionotropic (NR1 and GluR1) and metabotropic (mGluR1α) GluRs were detected in CMVEC by immunoblotting. Glutamate, aspartate, cis-ACPD, AMPA, ( RS)-2-amino-(3-hydroxy-5 -tert-butylisoxazol-4-yl)propanoic acid (ATPA), and kainate (10−5 mol/L) increased HO-directed CO formation by isolated cerebral microvessels and by cultured CMVEC. These data in newborn pigs suggest that CMVEC express ionotropic GluRs that are functionally linked to HO. GluR-mediated increases in CO formation by vascular endothelium may result in increase in cerebral blood flow.
44
Skowrońska, Katarzyna, Marta Obara-Michlewska, Magdalena Zielińska, and Jan Albrecht. "NMDA Receptors in Astrocytes: In Search for Roles in Neurotransmission and Astrocytic Homeostasis." International Journal of Molecular Sciences 20, no. 2 (January 14, 2019): 309. http://dx.doi.org/10.3390/ijms20020309.
Full textAbstract:
Studies of the last two decades have demonstrated the presence in astrocytic cell membranes of N-methyl-d-aspartate (NMDA) receptors (NMDARs), albeit their apparently low abundance makes demonstration of their presence and function more difficult than of other glutamate (Glu) receptor classes residing in astrocytes. Activation of astrocytic NMDARs directly in brain slices and in acutely isolated or cultured astrocytes evokes intracellular calcium increase, by mutually unexclusive ionotropic and metabotropic mechanisms. However, other than one report on the contribution of astrocyte-located NMDARs to astrocyte-dependent modulation of presynaptic strength in the hippocampus, there is no sound evidence for the significant role of astrocytic NMDARs in astrocytic-neuronal interaction in neurotransmission, as yet. Durable exposure of astrocytic and neuronal co-cultures to NMDA has been reported to upregulate astrocytic synthesis of glutathione, and in this way to increase the antioxidative capacity of neurons. On the other hand, overexposure to NMDA decreases, by an as yet unknown mechanism, the ability of cultured astrocytes to express glutamine synthetase (GS), aquaporin-4 (AQP4), and the inward rectifying potassium channel Kir4.1, the three astroglia-specific proteins critical for homeostatic function of astrocytes. The beneficial or detrimental effects of astrocytic NMDAR stimulation revealed in the in vitro studies remain to be proven in the in vivo setting.
45
Lohr, C., and J. W. Deitmer. "Intracellular Ca2+ release mediated by metabotropic glutamate receptor activation in the leech giant glial cell." Journal of Experimental Biology 200, no. 19 (October 1, 1997): 2565–73. http://dx.doi.org/10.1242/jeb.200.19.2565.
Full textAbstract:
We have investigated the effects of glutamate and glutamate receptor ligands on the intracellular free Ca2+ concentration ([Ca2+]i) and the membrane potential (Em) of single, identified neuropile glial cells in the central nervous system of the leech Hirudo medicinalis. Exposed glial cells of isolated ganglia were filled iontophoretically with the Ca2+ indicator dye Fura-2. Application of glutamate (200-500 mumoll-1) caused biphasic membrane potential shifts and increases in [Ca2+]i, which were only partly reduced by either removing extracellular Ca2+ or blocking ionotropic glutamate receptors with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 50-100 mumol l-1. Metabotropic glutamate receptor (mGluR) ligands had the following rank of potency in inducing a rise in [Ca2+]i: quisqualate (QQ, 200 mumol l-1) > glutamate (200 mumol l-1) > L(+)2-amino-3-phosphonopropionic acid (L-AP3, 200 mumol l-1 > trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD, 400 mumol l-1). The mGluR-selective antagonist (RS)-alpha-methyl-4-carboxyphenylglycine [(RS)-MCPG, 1 mmol l-1] significantly reduced glutamate-evoked increases in [Ca2+]i by 20%. Incubation of the ganglia with the endoplasmic ATPase inhibitor cyclopiazonic acid (CPA, 10 mumol l-1) caused a significant (53%) reduction of glutamate-induced [Ca2+]i transients, while incubation with lithium ions (2 mmol l-1) resulted in a 46% reduction. The effects of depleting the Ca2+ stores with CPA and of CNQX were additive. We conclude that glutamate-induced [Ca2+]i transients were mediated by activation of both Ca(2+)-permeable ionotropic non-NMDA receptors and of metabotropic glutamate receptors leading to Ca2+ release from intracellular Ca2+ stores.
46
KALLONIATIS, MICHAEL, DANIEL SUN, LISA FOSTER, SILKE HAVERKAMP, and HEINZ WÄSSLE. "Localization of NMDA receptor subunits and mapping NMDA drive within the mammalian retina." Visual Neuroscience 21, no. 4 (July 2004): 587–97. http://dx.doi.org/10.1017/s0952523804214080.
Full textAbstract:
Glutamate is a major neurotransmitter in the retina and other parts of the central nervous system, exerting its influence through ionotropic and metabotropic receptors. One ionotropic receptor, the N-methyl-D-aspartate (NMDA) receptor, is central to neural shaping, but also plays a major role during neuronal development and in disease processes. We studied the distribution pattern of different subunits of the NMDA receptor within the rat retina including quantifying the pattern of labelling for all the NR1 splice variants, the NR2A and NR2B subunits. The labelling pattern for the subunits was confined predominantly in the outer two-thirds of the inner plexiform layer. We also wanted to probe NMDA receptor function using an organic cation, agmatine (AGB); a marker for cation channel activity. Although there was an NMDA concentration-dependent increase in AGB labelling of amacrine cells and ganglion cells, we found no evidence of functional NMDA receptors on horizontal cells in the peripheral rabbit retina, nor in the visual streak where the type A horizontal cell was identified by GABA labelling. Basal AGB labelling within depolarizing bipolar cells was also noted. This basal bipolar cell AGB labelling was not modulated by NMDA and was completely abolished by the use of L-2-amino-4-phosphono-butyric acid, which is known to hyperpolarize retinal depolarizing bipolar cells. AGB is therefore not only useful as a probe of ligand-gated drive, but can also identify neurons that have constitutively open cationic channels. In combination, the NMDA receptor subunit distribution pattern and the AGB gating experiments strongly suggests that this ionotropic glutamate receptor is functional in the cone-driven pathway of the inner retina.
47
Schrader, Laura A., Stephen P. Perrett, Lan Ye, and Michael J. Friedlander. "Substrates for Coincidence Detection and Calcium Signaling for Induction of Synaptic Potentiation in the Neonatal Visual Cortex." Journal of Neurophysiology 91, no. 6 (June 2004): 2747–64. http://dx.doi.org/10.1152/jn.00908.2003.
Full textAbstract:
Regulation of the efficacy of synaptic transmission by activity-dependent processes has been implicated in learning and memory as well as in developmental processes. We previously described transient potentiation of excitatory synapses onto layer 2/3 pyramidal neurons in the visual cortex that is induced by coincident presynaptic stimulation and postsynaptic depolarization. In the adult visual cortex, activation of N-methyl-d-aspartate (NMDA) glutamate receptors is necessary to induce this plasticity. These receptors act as coincidence detectors, sensing presynaptic glutamate release and postsynaptic depolarization, and cause an influx of Ca2+ that is necessary for the potentiation. In the neurons of the neonatal visual cortex, on the other hand, coincident presynaptic stimulation and postsynaptic depolarization induce stable long-term potentiation (LTP). In addition, reduced but significant LTP can be induced in many neurons in the presence of the NMDA receptor (NMDAR) antagonist, 2-amino-5-phosphonovaleric acid despite the Ca2+ requirement. Therefore there must be an alternative postsynaptic Ca2+ source and coincidence detection mechanism linked to the LTP induction mechanism in the neonatal cortex operating in addition to NMDARs. In this study, we find that in layer 2/3 pyramidal neurons, release of Ca2+ from inositol trisphosphate (InsP3) receptor-mediated intracellular stores and influx through voltage-gated Ca2+ channels (VGCCs) provide alternative postsynaptic Ca2+ sources. We hypothesize that InsP3Rs are coincidence detectors, sensing presynaptic glutamate release through linkage with group I metabotropic glutamate receptors (mGluRs), and depolarization, through VGCCs. We also find that the downstream protein kinases, PKA and PKC, have a role in potentiation in layer 2/3 pyramidal neurons of the neonatal visual cortex.
48
Flint, A. C., and B. W. Connors. "Two types of network oscillations in neocortex mediated by distinct glutamate receptor subtypes and neuronal populations." Journal of Neurophysiology 75, no. 2 (February 1, 1996): 951–57. http://dx.doi.org/10.1152/jn.1996.75.2.951.
Full textAbstract:
1. Two distinct forms of spontaneous synchronous oscillations were investigated with field potential recordings in slices of rat somatosensory cortex in vitro. 2. The first type of synchronous oscillation was activated by low extracellular [Mg2+] and had dominant frequencies of 8-12 Hz. It was abolished reversibly by the N-methyl-D-aspartate (NMDA) receptor antagonists D-2-amino-5-phosphonovaleric acid and was relatively unaffected by the non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX). The duration of oscillatory events was increased by blocking gamma-aminobuturic acid-A receptors with bicuculline or by activating metabotropic glutamate receptors with trans-1-aminocyclopentane-1,3-dicarboxylic acid. 3. A second form of synchronous oscillation was activated by acute application of kainic acid (10 microM), had dominant frequencies of 1-5 Hz, and was abolished reversibly by DNQX. Low concentrations of domoic acid mimicked the effects of kainate, but alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid or quisqualic acid did not, suggesting a role for the GluR5-7 and KA1-2 glutamate receptor subunits. 4. Surgical isolation of cortical layers showed that spontaneous NMDA receptor-dependent oscillations originated within layer 5 exclusively, but kainate receptor-dependent oscillations were uniquely generated by neurons in layers 2/3. 5. Our results suggest that neocortical neurons in layers 2/3 and layer 5 can independently generate two distinct forms of rhythmic population activity, each dependent upon activation of a different subtype of glutamate receptor.
49
Palazzo, E., I. Marabese, V. de Novellis, P. Oliva, F. Rossi, L. Berrino, F. sca Rossi, and S. Maione. "Metabotropic and NMDA glutamate receptors participate in the cannabinoid-induced antinociception." Neuropharmacology 40, no. 3 (March 2001): 319–26. http://dx.doi.org/10.1016/s0028-3908(00)00160-x.
Full text
50
Crooke-Rosado, Jonathan L., Sara C. Diaz-Mendez, Yamil E. Claudio-Roman, Nilsa M. Rivera, and Maria A. Sosa. "De novo assembly of the freshwater prawn Macrobrachium carcinus brain transcriptome for identification of potential targets for antibody development." PLOS ONE 16, no. 4 (April 9, 2021): e0249801. http://dx.doi.org/10.1371/journal.pone.0249801.
Full textAbstract:
Crustaceans are major constituents of aquatic ecosystems and, as such, changes in their behavior and the structure and function of their bodies can serve as indicators of alterations in their immediate environment, such as those associated with climate change and anthropogenic contamination. We have used bioinformatics and a de novo transcriptome assembly approach to identify potential targets for developing specific antibodies to serve as nervous system function markers for freshwater prawns of the Macrobrachium spp. Total RNA was extracted from brain ganglia of Macrobrachium carcinus freshwater prawns and Illumina Next Generation Sequencing was performed using an Eel Pond mRNA Seq Protocol to construct a de novo transcriptome. Sequencing yielded 97,202,662 sequences: 47,630,546 paired and 1,941,570 singletons. Assembly with Trinity resulted in 197,898 assembled contigs from which 30,576 were annotated: 9,600 by orthology, 17,197 by homology, and 3,779 by transcript families. We looked for glutamate receptors contigs, due to their main role in crustacean excitatory neurotransmission, and found 138 contigs related to ionotropic receptors, 32 related to metabotropic receptors, and 18 to unidentified receptors. After performing multiple sequence alignments within different biological organisms and antigenicity analysis, we were able to develop antibodies for prawn AMPA ionotropic glutamate receptor 1, metabotropic glutamate receptor 1 and 4, and ionotropic NMDA glutamate receptor subunit 2B, with the expectation that the availability of these antibodies will help broaden knowledge regarding the underlying structural and functional mechanisms involved in prawn behavioral responses to environmental impacts. The Macrobrachium carcinus brain transcriptome can be an important tool for examining changes in many other nervous system molecules as a function of developmental stages, or in response to particular conditions or treatments.