scholarly journals Metabotropic actions of kainate receptors modulating glutamate release

2021 ◽  
pp. 108696
Author(s):  
Rafael Falcón-Moya ◽  
Antonio Rodríguez-Moreno
Keyword(s):  
Glutamate Release ◽  
Kainate Receptors

scholarly journals Excitotoxic Mechanisms of Ischemic Injury in Myelinated White Matter

2007 ◽  
Vol 27 (9) ◽  
pp. 1540-1552 ◽  
Author(s):  
Selva Baltan Tekkök ◽  
ZuCheng Ye ◽  
Bruce R Ransom
Keyword(s):  
White Matter ◽  
High Performance ◽  
Glutamate Release ◽  
Glutamate Transporter ◽  
Ischemic Injury ◽  
Glucose Deprivation ◽  
Kainate Receptors ◽  
Adult Mice ◽  
Direct Exposure ◽  
Glutamate Receptor Agonist

Axonal injury and dysfunction in white matter (WM) are caused by many neurologic diseases including ischemia. We characterized ischemic injury and the role of glutamate-mediated excitotoxicity in a purely myelinated WM tract, the mouse optic nerve (MON). For the first time, excitotoxic WM injury was directly correlated with glutamate release. Oxygen and glucose deprivation (OGD) caused duration-dependent loss of axon function in optic nerves from young adult mice. Protection of axon function required blockade of both α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate receptors, or removal of extracellular Ca2+. Blockade of N-methyl-D-aspartate receptors did not preserve axon function. Curiously, even extended periods of direct exposure to glutamate or kainate or AMPA failed to induce axon dysfunction. Brief periods of OGD, however, caused glutamate receptor agonist exposure to become toxic, suggesting that ionic disruption enabled excitotoxic injury. Glutamate release, directly measured using quantitative high-performance liquid chromatography, occurred late during a 60-mins period of OGD and was due to reversal of the glutamate transporter. Brief periods of OGD (i.e., 15 mins) did not cause glutamate release and produced minimal injury. These results suggested that toxic glutamate accumulation during OGD followed the initial ionic changes mediating early loss of excitability. The onset of glutamate release was an important threshold event for irreversible ischemic injury. Regional differences appear to exist in the specific glutamate receptors that mediate WM ischemic injury. Therapy for ischemic WM injury must be designed accordingly.

Spontaneous Oscillatory Activity of Starburst Amacrine Cells in the Mouse Retina

2005 ◽  
Vol 94 (3) ◽  
pp. 1770-1780 ◽  
Author(s):  
Jerome Petit-Jacques ◽  
Béla Völgyi ◽  
Bernardo Rudy ◽  
Stewart Bloomfield
Keyword(s):  
Feedback Inhibition ◽  
Glutamate Release ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Kainate Receptors ◽  
Oscillatory Activity ◽  
Mouse Retina ◽  
Inner Plexiform Layer ◽  
Experimental Conditions ◽  
Starburst Amacrine Cells

Using patch-clamp techniques, we investigated the characteristics of the spontaneous oscillatory activity displayed by starburst amacrine cells in the mouse retina. At a holding potential of –70 mV, oscillations appeared as spontaneous, rhythmic inward currents with a frequency of ∼3.5 Hz and an average maximal amplitude of ∼120 pA. Application of TEA, a potassium channel blocker, increased the amplitude of oscillatory currents by >70% but reduced their frequency by ∼17%. The TEA effects did not appear to result from direct actions on starburst cells, but rather a modulation of their synaptic inputs. Oscillatory currents were inhibited by 6-cyano-7-nitroquinoxalene-2,3-dione (CNQX), an antagonist of AMPA/kainate receptors, indicating that they were dependent on a periodic glutamatergic input likely from presynaptic bipolar cells. The oscillations were also inhibited by the calcium channel blockers cadmium and nifedipine, suggesting that the glutamate release was calcium dependent. Application of AP4, an agonist of mGluR6 receptors on on-center bipolar cells, blocked the oscillatory currents in starburst cells. However, application of TEA overcame the AP4 blockade, suggesting that the periodic glutamate release from bipolar cells is intrinsic to the inner plexiform layer in that, under experimental conditions, it can occur independent of photoreceptor input. The GABA receptor antagonists picrotoxin and bicuculline enhanced the amplitude of oscillations in starburst cells prestimulated with TEA. Our results suggest that this enhancement was due to a reduction of a GABAergic feedback inhibition from amacrine cells to bipolar cells and the resultant increased glutamate release. Finally, we found that some ganglion cells and other types of amacrine cell also displayed rhythmic activity, suggesting that oscillatory behavior is expressed by a number of inner retinal neurons.

scholarly journals Non-canonical Mechanisms of Presynaptic Kainate Receptors Controlling Glutamate Release

2018 ◽  
Vol 11 ◽  
Author(s):  
José V. Negrete-Díaz ◽  
Talvinder S. Sihra ◽  
Gonzalo Flores ◽  
Antonio Rodríguez-Moreno
Keyword(s):  
Glutamate Release ◽  
Kainate Receptors

Kainate Receptor–Induced Ectopic Spiking of CA3 Pyramidal Neurons Initiates Network Bursts in Neonatal Hippocampus

2010 ◽  
Vol 104 (3) ◽  
pp. 1696-1706 ◽  
Author(s):  
Juuso Juuri ◽  
Vernon R. J. Clarke ◽  
Sari E. Lauri ◽  
Tomi Taira
Keyword(s):  
Pyramidal Neurons ◽  
Glutamate Release ◽  
Physiological Role ◽  
Network Activity ◽  
Kainate Receptors ◽  
Natural Activity ◽  
High Affinity ◽  
Network Bursts ◽  
Ca3 Pyramidal Neurons ◽  
Endogenous Activity

Kainate receptors (KARs) are expressed at high levels in the brain during early development and may be critical for the proper development of neuronal networks. Here we elucidated a physiological role of high-affinity KARs in developing hippocampal network by studying the effects of 25–100 nM kainate (KA) on intrinsic network activity in slice preparations. Whereas 100 nM KA resulted in hyperexcitability of the network and the disruption of natural activity patterns, ≤50 nM KA concentrations enhanced the initiation of network bursts yet preserved the characteristic patterns of endogenous activity. This was not dependent on changes in GABAergic transmission or on activation of GluK1 subunit containing KARs. However, the activation of high-affinity KARs increased glutamatergic drive by promoting spontaneous firing of CA3 pyramidal neurons without affecting action potential independent glutamate release. This was not because of changes in the intrinsic somatic properties of pyramidal neurons but seemed to reside in an electrically remote site, most probably in an axonal compartment. Although application of KAR agonists has mainly been used to study pathological type of network activities, this study provides a novel mechanism by which endogenous activity of KARs can modulate intrinsic activities of the emerging neuronal network in a physiologically relevant manner. The results support recent studies that KARs play a central role in the activity-dependent maturation of synaptic circuitries.

scholarly journals Kainate Receptor–Mediated Inhibition of Glutamate Release Involves Protein Kinase A in the Mouse Hippocampus

2006 ◽  
Vol 96 (4) ◽  
pp. 1829-1837 ◽  
Author(s):  
José V. Negrete-Díaz ◽  
Talvinder S. Sihra ◽  
José M. Delgado-García ◽  
Antonio Rodríguez-Moreno
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Mossy Fiber ◽  
Glutamate Release ◽  
Pyramidal Cells ◽  
Kainate Receptors ◽  
Mouse Hippocampus ◽  
Ca3 Pyramidal Cells ◽  
Kinase A ◽  
Stimulation Of

The mechanisms involved in the inhibition of glutamate release mediated by the activation of presynaptic kainate receptors (KARs) at the hippocampal mossy fiber–CA3 synapse are not well understood. We have observed a long-lasting inhibition of CA3 evoked excitatory postsynaptic currents (eEPSCs) after a brief application of kainate (KA) at concentrations ranging from 0.3 to 10 μM. The inhibition outlasted the change in holding current caused by the activation of ionotropic KARs in CA3 pyramidal cells, indicating that this action is not contingent on the opening of the receptor channels. The inhibition of the eEPSCs by KA was prevented by G protein and protein kinase A (PKA) inhibitors and was enhanced after stimulation of the adenylyl cyclase (AC) with forskolin. We conclude that KARs present at mossy fiber terminals mediate the inhibition of glutamate release through a metabotropic mechanism that involves the activation of an AC-second messenger cAMP-PKA signaling cascade.

scholarly journals Kainate Receptors Modulating Glutamate Release in the Cerebellum

2019 ◽  
Author(s):  
Pilar Losada-Ruiz ◽  
Rafael Falcón-Moya ◽  
Antonio Rodríguez-Moreno
Keyword(s):  
Glutamate Release ◽  
Kainate Receptors

scholarly journals Kainate receptors regulate development of glutamatergic synaptic circuitry in the rodent amygdala

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Maria Ryazantseva ◽  
Jonas Englund ◽  
Alexandra Shintyapina ◽  
Johanna Huupponen ◽  
Vasilii Shteinikov ◽  
...  
Keyword(s):  
Information Processing ◽  
Genetic Manipulation ◽  
Glutamate Release ◽  
Physiological Mechanism ◽  
Kainate Receptors ◽  
Ionotropic Glutamate Receptors ◽  
Synaptic Development ◽  
Synaptic Circuitry ◽  
Amygdaloid Nuclei ◽  
Dependent Mechanism

Perturbed information processing in the amygdala has been implicated in developmentally originating neuropsychiatric disorders. However, little is known on the mechanisms that guide formation and refinement of intrinsic connections between amygdaloid nuclei. We demonstrate that in rodents the glutamatergic connection from basolateral to central amygdala (BLA-CeA) develops rapidly during the first 10 postnatal days, before external inputs underlying amygdala-dependent behaviors emerge. During this restricted period of synaptic development, kainate-type of ionotropic glutamate receptors (KARs) are highly expressed in the BLA and tonically activated to regulate glutamate release via a G-protein-dependent mechanism. Genetic manipulation of this endogenous KAR activity locally in the newborn LA perturbed development of glutamatergic input to CeA, identifying KARs as a physiological mechanism regulating formation of the glutamatergic circuitry in the amygdala.

Regulation of glutamate release by presynaptic kainate receptors in the hippocampus

Nature ◽  
1996 ◽  
Vol 379 (6560) ◽  
pp. 78-81 ◽  
Author(s):  
Ramesh Chittajallu ◽  
Michel Vignes ◽  
Kumlesh K. Dev ◽  
Janine M. Barnes ◽  
Graham L. Collingridge ◽  
...  
Keyword(s):  
Glutamate Release ◽  
Kainate Receptors

Localization of kainate receptors to the presynaptic active zone of the rod photoreceptor in primate retina

2002 ◽  
Vol 19 (5) ◽  
pp. 681-692 ◽  
Author(s):  
D.M. HARVEY ◽  
D.J. CALKINS
Keyword(s):  
Active Zone ◽  
Visual Information ◽  
Axon Terminal ◽  
Glutamate Release ◽  
Kainate Receptors ◽  
Rod Photoreceptor ◽  
Axon Terminals ◽  
Physiological Properties ◽  
Photoreceptor Synapse ◽  
Presynaptic Active Zone

Visual information is encoded at the photoreceptor synapse by modulation of the tonic release of glutamate from one or more electron-dense ribbons. This release is highest in the dark, when photoreceptors are depolarized, and decreases in grades when photoreceptors hyperpolarize with increasing light. Functional diversity between neurons postsynaptic at the synaptic ribbon arises in part from differential expression of both metabotropic (G-protein-gated) and ionotropic (ligand-gated) glutamate receptor. In the brain, different subunits also modulate the presynaptic active zone. In hippocampus, ionotropic kainate receptors localize to the presynaptic membrane of glutamatergic axon terminals and facilitate depolarization of the synapse (e.g. Lauri et al., 2001). Such facilitation may be helpful in the retina, where consistent depolarization of the photoreceptor axon terminal is necessary to maintain glutamate release in the dark. We investigated whether such a mechanism could be present in primate retina by using electron microscopy to examine the localization of the kainate subunits GluR6/7 at the rod axon terminal, where only a single ribbon synapse mediates glutamate release. We scored 54 rod axon terminals whose postsynaptic space contained one or more GluR6/7-labeled processes and traced these processes through serial sections to determine their identity. Of 68 labeled processes, 63% originated from narrow “fingers” of cytoplasm extending from the presynaptic axon terminal into the postsynaptic cleft. Each rod terminal typically inserts 4–6 presynaptic fingers, and we scored several instances where multiple fingers contained label. Such consistency suggests that each presynaptic finger expresses GluR6/7. The physiological properties of kainate receptors and the geometry of the rod axon terminal suggest that presynaptic GluR6/7 could provide a steady inward current to maintain consistent depolarization of the rod synapse in the long intervals between photons in the dark.

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