scholarly journals Ionotropic glutamate receptors in the external lateral parabrachial nucleus participate in processing cardiac sympathoexcitatory reflexes

2012 ◽  
Vol 302 (7) ◽  
pp. H1444-H1453 ◽  
Author(s):  
Liang-Wu Fu ◽  
Zhi-Ling Guo ◽  
John C. Longhurst
Keyword(s):  
Glutamate Receptors ◽  
Glutamate Receptor ◽  
Ampa Receptors ◽  
Repeated Administration ◽  
Parabrachial Nucleus ◽  
Ionotropic Glutamate Receptors ◽  
Reflex Responses ◽  
Lateral Parabrachial Nucleus ◽  
Artificial Cerebrospinal Fluid ◽  
Before And After

Stimulation of cardiac sympathetic afferents during myocardial ischemia with metabolites such as bradykinin (BK) evokes sympathoexcitatory reflex responses and activates neurons in the external lateral parabrachial nucleus (elPBN). The present study tested the hypothesis that this region in the pons processes sympathoexcitatory cardiac reflexes through an ionotropic glutamate receptor mechanism. The ischemic metabolite BK (0.1–1 μg) was injected into the pericardial space of anesthetized and bilaterally vagotomized or intact cats. Hemodynamic and renal sympathetic nerve activity (RSNA) responses to repeated administration of BK before and after unilateral 50-nl microinjections of kynurenic acid (Kyn; 25 mM), 2-amino-5-phosphonopentanoic acid (AP5; 25 mM), and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzol(F)quinoxaline (NBQX; 10 mM) into the elPBN were recorded. Intrapericardial BK evoked significant increases in mean arterial pressure (MAP) and RSNA in seven vagotomized cats. After blockade of glutamate receptors with the nonselective glutamate receptor antagonist Kyn, the BK-evoked reflex increases in MAP (50 ± 6 vs. 29 ± 2 mmHg) and RSNA (59 ± 8.6 vs. 29 ± 4.7%, before vs. after) were significantly attenuated. The BK-evoked responses returned to pre-Kyn levels 85 min after the application of Kyn. Similarly, BK-evoked reflex responses were reversibly attenuated by blockade of glutamate N-methyl-d-aspartate (NMDA) receptors with AP5 ( n = 5) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors with NBQX ( n = 5). In contrast, we observed that the repetitive administration of BK evoked consistent reflex responses including MAP and RSNA before and after microinjection of 50 nl of the artificial cerebrospinal fluid vehicle into the elPBN in five animals. Microinjection of glutamate receptor antagonists into regions outside the elPBN did not alter BK-induced reflex responses. Microinjection of Kyn into the elPBN reversibly attenuated BK-induced reflex responses in four vagus intact animals. These data are the first to show that NMDA and AMPA ionotropic glutamate receptors in the elPBN play an important role in processing cardiac excitatory reflex responses.

scholarly journals More than meets the IR: the expanding roles of variant Ionotropic Glutamate Receptors in sensing odor, taste, temperature and moisture

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1753 ◽  
Author(s):  
Lena van Giesen ◽  
Paul A. Garrity
Keyword(s):  
Glutamate Receptors ◽  
Glutamate Receptor ◽  
Olfactory Receptors ◽  
Sensory Transduction ◽  
Ionotropic Glutamate Receptors ◽  
Ionotropic Glutamate Receptor ◽  
Ecological Significance ◽  
Ionotropic Receptors ◽  
Sensory Modalities ◽  
Receptor Family

The ionotropic receptors (IRs) are a branch of the ionotropic glutamate receptor family and serve as important mediators of sensory transduction in invertebrates. Recent work shows that, though initially studied as olfactory receptors, the IRs also mediate the detection of taste, temperature, and humidity. Here, we summarize recent insights into IR evolution and its potential ecological significance as well as recent advances in our understanding of how IRs contribute to diverse sensory modalities.

scholarly journals UNDERSTANDING THE PHYSIOLOGY OF GLUTAMATE RECEPTORS BY USE OF A PROTOCOL FOR NEURONAL STAINING

2003 ◽  
Vol 27 (2) ◽  
pp. 78-85 ◽  
Author(s):  
João O. Malva ◽  
Ana P. Vieira ◽  
Catarina R. Oliveira
Keyword(s):  
Glutamate Receptors ◽  
Ampa Receptors ◽  
Complex Analysis ◽  
Ionotropic Glutamate Receptors ◽  
Neurotransmitter Receptors ◽  
Cultured Neurons ◽  
Bright Field ◽  
Dendritic Network ◽  
Sophisticated Equipment ◽  
Bright Field Microscopy

Teaching students about the physiology of neurotransmitter receptors usually requires practical lessons with the use of sophisticated equipment and complex analysis of data. Here, we report our experience in teaching medical students with a simple, practical protocol that transforms the physiology of glutamate receptors into neuronal staining, observable under bright-field microscopy. Essentially, the students were challenged to selectively stain a subpopulation of cultured neurons expressing Ca2+-permeable α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors (a subgroup of ionotropic glutamate receptors). Neurons expressing this type of receptors were loaded with Co2+ (in substitution for Ca2+) after nondesensitizing activation of AMPA receptors. After precipitation, the Co2+ was revealed after treatment with silver. At the end of the procedure, the neurons expressing Ca2+-permeable AMPA receptors were visually identified under bright-field microscopy. The procedure allowed the visualization of the complete dendritic network of the stained neurons and allowed the students to learn very efficiently about the physiology of glutamate receptors.

Peptides in the parabrachial nucleus modulate visceral input to the thalamus

1993 ◽  
Vol 264 (4) ◽  
pp. R668-R675 ◽  
Author(s):  
T. M. Saleh ◽  
D. F. Cechetto
Keyword(s):  
Neuronal Activity ◽  
Vagal Stimulation ◽  
Fold Increase ◽  
Parabrachial Nucleus ◽  
Artificial Cerebrospinal Fluid ◽  
Calcitonin Gene ◽  
Before And After ◽  
Male Wistar Rats ◽  
Sensory Pathway

The role of neuropeptides in ascending visceral pathways was investigated by recording the changes in the response of thalamic neuronal activity evoked by vagal stimulation before and after peptide injection in the parabrachial nucleus (PB). Male Wistar rats (n = 25) were anesthetized with chloral hydrate and ventilated, and blood pressure and heart rate were continuously monitored. The left cervical vagus nerve was stimulated at submaximal current intensities to elicit changes in single and multiunit activity in the parvocellular visceral relay nuclei in the ventral basal thalamus. Peristimulustime histograms of thalamic activity were made before and after 200-nl injections of peptides or artificial cerebrospinal fluid (CSF) controls in the PB. Injection of calcitonin gene-related peptide (CGRP) at 5 mM or substance P (SP) at 2 mM into the PB significantly attenuated the evoked response of thalamic neuronal activity by 87-100% and 85-100%, respectively. Injections of somatostatin (SOM; 1 mM) did not significantly alter the response evoked by vagal stimulation but significantly inhibited the spontaneous firing of thalamic units, resulting in a 10-fold increase in the response-to-background ratio. This suggests that SOM in the PB inhibits cells in a parallel pathway that terminates on thalamic visceral neurons but that are not part of the ascending visceral sensory pathway. Spontaneous thalamic neuronal activity and vagally evoked responses were significantly enhanced (278-508%) by injection of 1 mM neurotensin (NT) in the PB. Cholecystokinin (CCK) at low doses (0.0002-0.2 mM) attenuated while the highest dose, 2 mM, briefly excited the spontaneous activity of thalamic units before inhibiting their activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Gabapentin is neuroprotective through glutamate receptor-independent mechanisms in staurosporine-induced apoptosis of cultured rat cerebellar neurons

2013 ◽  
Vol 4 (4) ◽  
Author(s):  
Bogdan Popescu ◽  
Maria Ţuineag ◽  
Radu Stoica
Keyword(s):  
Glutamate Receptors ◽  
Glutamate Receptor ◽  
Ampa Receptors ◽  
Kinase Inhibitor ◽  
Neuronal Cell ◽  
Morphological Aspect ◽  
Cerebellar Granule Neuron ◽  
Neuronal Cell Adhesion Molecule ◽  
Apoptotic Pathways ◽  
Induced Apoptosis

AbstractThe anticonvulsants that are currently available modulate the activity of neuronal receptors and ion channels, which are equally involved in apoptotic pathways. We investigated the hypothesis that gabapentin (GP), an anticonvulsant without effect on glutamate receptors acting as GABA analog, has neuroprotective properties. For comparison, we chose topiramate (TPM), which has been reported to be neuroprotective via AMPA receptors blockade. For this purpose, we used rat cerebellar granule neuron (CGN) cultures and we triggered apoptosis independent of glutamate receptors with staurosporine, a broad-spectrum protein kinase inhibitor. GP at therapeutic range concentration significantly increased cell viability in CGN cultures maintained in physiological KCl concentration and reversed apoptosis induced by staurosporine. Blockade of NMDA or AMPA receptors by MK801 or NBQX, respectively, did not alter GP neuroprotection, which was reversed instead by GABA. In contrast, protective effect of TPM on STS-treated CGN cultures was annihilated by NBQX, and not altered by MK801 or GABA. Treatments with neuroprotective concentrations of GP or TPM did not modify the expression of neuronal cell adhesion molecule or synaptophysin or the morphological aspect of neuronal endings. In summary, we report that GP is neuroprotective through glutamate-receptor independent mechanisms and without alteration of neuronal plasticity markers, which makes it a possible candidate for clinical neuroprotection trials.

Distribution, Density, and Clustering of Functional Glutamate Receptors Before and After Synaptogenesis in Hippocampal Neurons

2000 ◽  
Vol 84 (3) ◽  
pp. 1573-1587 ◽  
Author(s):  
Jeffrey R. Cottrell ◽  
Gilles R. Dubé ◽  
Christophe Egles ◽  
Guosong Liu
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Glutamate Receptors ◽  
Glutamate Receptor ◽  
Ampa Receptors ◽  
Hippocampal Neurons ◽  
Time Course ◽  
Synapse Formation ◽  
Receptor Activation ◽  
Receptor Density

Postsynaptic differentiation during glutamatergic synapse formation is poorly understood. Using a novel biophysical approach, we have investigated the distribution and density of functional glutamate receptors and characterized their clustering during synaptogenesis in cultured hippocampal neurons. We found that functional α-amino-3-hydroxy-5-methyl-4-isoxazolpropionate (AMPA) and N-methyl-d-aspartate (NMDA) receptors are evenly distributed in the dendritic membrane before synaptogenesis with an estimated density of 3 receptors/μm2. Following synaptogenesis, functional AMPA and NMDA receptors are clustered at synapses with a density estimated to be on the order of 104 receptors/μm2, which corresponds to ∼400 receptors/synapse. Meanwhile there is no reduction in the extrasynaptic receptor density, which indicates that the aggregation of the existing pool of receptors is not the primary mechanism of glutamate receptor clustering. Furthermore our data suggest that the ratio of AMPA to NMDA receptor density may be regulated to be close to one in all dendritic locations. We also demonstrate that synaptic AMPA and NMDA receptor clusters form with a similar time course during synaptogenesis and that functional AMPA receptors cluster independently of activity and glutamate receptor activation, including following the deletion of the NMDA receptor NR1 subunit. Thus glutamate receptor activation is not necessary for the insertion, clustering, and activation of functional AMPA receptors during synapse formation, and this process is likely controlled by an activity-independent signal.

scholarly journals Neurosteroid modulation of ionotropic glutamate receptors and excitatory synaptic transmission

2008 ◽  
pp. S49-S57
Author(s):  
M Sedláček ◽  
M Kořínek ◽  
M Petrovič ◽  
O Cais ◽  
E Adamusová ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Nmda Receptors ◽  
Glutamate Receptors ◽  
Ampa Receptors ◽  
Transmembrane Domain ◽  
Kainate Receptors ◽  
Ionotropic Glutamate Receptors ◽  
Extracellular Loop ◽  
Inhibitory Effects ◽  
Chimeric Receptors

Ionotropic glutamate receptors function can be affected by neurosteroids, both positively and negatively. N-methyl-D-aspartate (NMDA) receptor responses to exogenously applied glutamate are potentiated or inhibited (depending on the receptor subunit composition) by pregnenolone sulphate (PS) and inhibited by pregnanolone sulphate (3alpha5betaS). While PS effect is most pronounced when its application precedes that of glutamate, 3alpha5betaS only binds to receptors already activated. Synaptically activated NMDA receptors are inhibited by 3alpha5betaS, though to a lesser extent than those tonically activated by exogenous glutamate. PS, on the other hand, shows virtually no effect on any of the models of synaptically activated NMDA receptors. The site of neurosteroid action at the receptor molecule has not yet been identified, however, the experiments indicate that there are at least two distinct extracellularly located binding sites for PS mediating its potentiating and inhibitory effects respectively. Experiments with chimeric receptors revealed the importance of the extracellular loop connecting the third and the fourth transmembrane domain of the receptor NR2 subunit for the neurosteroid action. alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptors are inhibited by both PS and 3alpha5betaS. These neurosteroids also affect AMPA receptors-mediated synaptic transmission, however, in a rather indirect way, through presynaptically located targets of action.

scholarly journals Changes in glutamate receptors in dyskinetic parkinsonian monkeys after unilateral subthalamotomy

2015 ◽  
Vol 123 (6) ◽  
pp. 1383-1393 ◽  
Author(s):  
Vincent A. Jourdain ◽  
Nicolas Morin ◽  
Laurent Grégoire ◽  
Marc Morissette ◽  
Thérèse Di Paolo
Keyword(s):  
Basal Ganglia ◽  
Glutamate Receptors ◽  
Ampa Receptors ◽  
Specific Binding ◽  
Postmortem Brain ◽  
Ionotropic Glutamate Receptors ◽  
Metabotropic Glutamate ◽  
Levodopa Treatment ◽  
Mglu5 Receptors ◽  
Surgical Treatments

OBJECT Unilateral subthalamotomy is a surgical procedure that may be used to alleviate disabling levodopa-induced dyskinesias (LIDs) in patients with Parkinson disease (PD). However, the mechanisms involved in LID remain largely unknown. The subthalamic nucleus (STN) is the sole glutamatergic nucleus within the basal ganglia, and its lesion may produce changes in glutamate receptors in various areas of the basal ganglia. The authors aimed to investigate the biochemical changes in glutamate receptors in striatal and pallidal regions of the basal ganglia after lesion of the STN in parkinsonian macaque monkeys. METHODS The authors treated 12 female ovariectomized monkeys with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD-like symptoms, treated 8 of these animals with 3,4-dihydroxy-l-phenylalanine (L-DOPA; levodopa) to induce LID, and performed unilateral subthalamotomy in 4 of these 8 monkeys. Four additional monkeys were treated with saline only and were used as controls. The MPTP monkeys had previously been shown to respond behaviorally to lower doses of levodopa after the STN lesion. Autoradiography of slices from postmortem brain tissues was used to visualize changes in the specific binding of striatal and pallidal ionotropic glutamate receptors (that is, of the α-amino-3-hydroxy 5-methyl-4-isoxazole propionate [AMPA] and N-methyl-d-aspartate [NMDA] NR1/NR2B subunit receptors) and of metabotropic glutamate (mGlu) receptors (that is, mGlu2/3 and mGlu5 receptors). The specific binding and distribution of glutamate receptors in the basal ganglia of the levodopa-treated, STN-lesioned MPTP monkeys were compared with those in the saline-treated control monkeys and in the saline-treated and levodopa-treated MPTP monkeys. RESULTS The autoradiographic results indicated that none of the pharmacological and surgical treatments produced changes in the specific binding of AMPA receptors in the basal ganglia. Levodopa treatment increased the specific binding of NMDA receptors in the basal ganglia. Subthalamotomy reversed these increases in the striatum, but in the globus pallidus (GP), the subthalamotomy reversed these increases only contralaterally. Levodopa treatment reversed MPTP-induced increases in mGlu2/3 receptors only in the GP. mGlu2/3 receptor–specific binding in the striatum and GP decreased bilaterally in the levodopa-treated, STN-lesioned MPTP monkeys compared with the other 3 groups. Compared with mGlu5 receptor–specific binding in the control monkeys, that of the levodopa-treated MPTP monkeys increased in the dorsal putamen and remained unchanged in the caudate nucleus and in the GP. CONCLUSIONS These results implicate glutamate receptors in the previously observed benefits of unilateral subthalamotomy to improve motor control.

AMPA receptor activation of area postrema neurons

1999 ◽  
Vol 276 (2) ◽  
pp. R586-R590 ◽  
Author(s):  
Meredith Hay ◽  
Kathy A. Lindsley
Keyword(s):  
Receptor Antagonist ◽  
Glutamate Receptors ◽  
Ampa Receptors ◽  
Area Postrema ◽  
Nmda Antagonist ◽  
Cytosolic Calcium ◽  
Receptor Activation ◽  
Ionotropic Glutamate Receptors ◽  
Maximal Response ◽  
Dose Dependent

This study reports on the effects of activation of ionotropic glutamate receptors on area postrema neuron cytosolic calcium concentration ([Ca2+]i). In 140 of 242 area postrema neurons isolated from postnatal rats, application of 100 μMl-glutamate (l-Glu) resulted in a significant increase in [Ca2+]i. The remaining neurons were unaffected. The effects ofl-Glu on area postrema [Ca2+]iwere dose dependent, with a threshold of response near 1.0 μM and maximal response near 100 μM. To determine if the response ofl-Glu in area postrema neurons was due to activation of ionotropic glutamate receptors, the effects of the broad-spectrum ionotropic glutamate receptor antagonist kynurinic acid (Kyn) was determined. Application of 1.0 mM Kyn resulted in a 62.6 ± 4% inhibition of thel-Glu-evoked response. Application of the selective N-methyl-d-aspartic acid (NMDA) antagonist 2-amino-5-phosphonopentanoic acid had no effect on the response of area postrema neurons to 100 μMl-Glu. In contrast, application of the selectivedl-α-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA)/kainate receptor antagonist 6,7-dinitroquinoxaline (DNQX) effectively blocked the 100 μMl-Glu response. Application of (±)-AMPA mimicked the effects observed withl-Glu and was selectively blocked by DNQX. These results suggest thatl-Glu activation of area postrema neurons involves activation of AMPA receptors but not NMDA receptors.

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