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.

scholarly journals Kainate-type of glutamate receptors regulate wiring of intrinsic glutamatergic connectivity in the amygdala

2019 ◽  
Author(s):  
Maria Ryazantseva ◽  
Jonas Englund ◽  
Alexandra Shintyapina ◽  
Johanna Huupponen ◽  
Asla Pitkänen ◽  
...  
Keyword(s):  
Information Processing ◽  
Glutamate Receptors ◽  
G Protein ◽  
Genetic Manipulation ◽  
Glutamate Release ◽  
Physiological Mechanism ◽  
Ionotropic Glutamate Receptors ◽  
Synaptic Development ◽  
Amygdaloid Nuclei ◽  
Dependent Mechanism

SummaryPerturbed 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 the glutamatergic connection from basolateral to central amygdala (BLA-CeA) develops rapidly during the first ten 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 wiring of the intrinsic glutamatergic circuitry in the amygdala.

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.

scholarly journals Downregulation of kainate receptors regulating GABAergic transmission in amygdala after early life stress is associated with anxiety-like behavior in rodents

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jonas Englund ◽  
Joni Haikonen ◽  
Vasilii Shteinikov ◽  
Shyrley Paola Amarilla ◽  
Tsvetomira Atanasova ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Kainate Receptors ◽  
Gabaergic Transmission ◽  
Cortical Afferents ◽  
Functional Modulation ◽  
Endogenous Activity ◽  
Dependent Mechanism

AbstractEarly life stress (ELS) is a well-characterized risk factor for mood and anxiety disorders. GABAergic microcircuits in the amygdala are critically implicated in anxiety; however, whether their function is altered after ELS is not known. Here we identify a novel mechanism by which kainate receptors (KARs) modulate feedforward inhibition in the lateral amygdala (LA) and show that this mechanism is downregulated after ELS induced by maternal separation (MS). Specifically, we show that in control rats but not after MS, endogenous activity of GluK1 subunit containing KARs disinhibit LA principal neurons during activation of cortical afferents. GluK1 antagonism attenuated excitability of parvalbumin (PV)-expressing interneurons, resulting in loss of PV-dependent inhibitory control and an increase in firing of somatostatin-expressing interneurons. Inactivation of Grik1 expression locally in the adult amygdala reduced ongoing GABAergic transmission and was sufficient to produce a mild anxiety-like behavioral phenotype. Interestingly, MS and GluK1-dependent phenotypes showed similar gender specificity, being detectable in male but not female rodents. Our data identify a novel KAR-dependent mechanism for cell-type and projection-specific functional modulation of the LA GABAergic microcircuit and suggest that the loss of GluK1 KAR function contributes to anxiogenesis after ELS.

Metabolic and Tissue Solute Changes Associated With Changes in the Freezing Tolerance of the Bivalve Mollusc Modiolus Demissus

1977 ◽  
Vol 69 (1) ◽  
pp. 1-12
Author(s):  
DENNIS J. MURPHY
Keyword(s):  
Oxygen Consumption ◽  
Low Temperature ◽  
Freezing Tolerance ◽  
Anaerobic Metabolism ◽  
Arrhenius Plot ◽  
Physiological Mechanism ◽  
Temperature Acclimation ◽  
Anaerobic Conditions ◽  
Rate Of Oxygen Consumption ◽  
Dependent Mechanism

1. A physiological mechanism responsible for increasing the freezing tolerance of the bivalve Modiolus demissus (Dillwyn) following low-temperature acclimation was demonstrated. 2. The rates of oxygen consumption of M. demissus acclimated to temperatures between 0 and 24 °C were presented as an Arrhenius plot. A change in slope occurred at 10 °C, suggesting that temperature alone was not responsible for the increased decline in the rate of oxygen consumption below 10 °C. 3. Low-temperature acclimation had no effect on blood Na+ or K+ concentrations but did reduce the concentration of blood Mg2+ and, in addition, resulted in the accumulation of end-products characteristic of anaerobic metabolism - tissue alanine and proline, and blood Ca2+. Furthermore, maintenance of M. demissus under anaerobic conditions increased freezing tolerance. 4. Taken together, these data indicate that the increased freezing tolerance of M. demissus acclimated to low temperatures involves a conversion to anaerobic metabolism. 5. The increase in blood Ca2+ following low-temperature acclimation was associated with the increased freezing tolerance. Finally, Mg2+ simulated the effect of Ca2+ on freezing tolerance, but was only 20% as effective. 6. These results suggest that a Ca2+-dependent mechanism responsible for increasing the freezing tolerance of M. demissus exists, and that the increase in blood Ca2+ is due to a conversion to anaerobic metabolism.

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 Secreted Euryarchaeal Microhalocins Kill Hyperthermophilic Crenarchaea

2001 ◽  
Vol 183 (1) ◽  
pp. 287-291 ◽  
Author(s):  
Cynthia Haseltine ◽  
Tiffany Hill ◽  
Rafael Montalvo-Rodriguez ◽  
Samantha K. Kemper ◽  
Richard F. Shand ◽  
...  
Keyword(s):  
Potassium Chloride ◽  
Genetic Manipulation ◽  
Sulfolobus Solfataricus ◽  
Peptide Antibiotic ◽  
Secreted Protein ◽  
Toxic Factor ◽  
Genetic Studies ◽  
Assay Medium ◽  
Resistant Mutants ◽  
Dependent Mechanism

ABSTRACT Few antibiotics targeting members of the archaeal domain are currently available for genetic studies. Since bacterial antibiotics are frequently directed against competing and related organisms, archaea by analogy might produce effective antiarchaeal antibiotics. Peptide antibiotic (halocin) preparations from euryarchaeal halophilic strains S8a, GN101, and TuA4 were found to be toxic for members of the hyperthermophilic crenarchaeal genus Sulfolobus. No toxicity was evident against representative bacteria or eukarya. Halocin S8 (strain S8a) and halocin R1 (strain GN101) preparations were cytostatic, while halocin A4 (strain TuA4) preparations were cytocidal. Subsequent studies focused on the use of halocin A4 preparations andSulfolobus solfataricus. Strain TuA4 cell lysates were not toxic for S. solfataricus, and protease (but not nuclease) treatment of the halocin A4 preparation inactivated toxicity, indicating that the A4 toxic factor must be a secreted protein. Potassium chloride supplementation of the Sulfolobus assay medium potentiated toxicity, implicating use of a salt-dependent mechanism. The utility of halocin A4 preparations for genetic manipulation of S. solfataricus was assessed through the isolation of UV-induced resistant mutants. The mutants exhibited stable phenotypes and were placed into distinct classes based on their levels of resistance.

scholarly journals Increased expression of fragmented tRNA promoted neuronal necrosis

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Yanyan Cao ◽  
Kai Liu ◽  
Ying Xiong ◽  
Chunyue Zhao ◽  
Lei Liu
Keyword(s):  
Cell Death ◽  
Glutamate Receptor ◽  
Small Rna ◽  
Genetic Manipulation ◽  
Glutamate Release ◽  
Mitochondrial Fission ◽  
Receptor Activation ◽  
Small Rna Sequencing ◽  
Neuronal Necrosis ◽  
A Genome

AbstractNeuronal necrosis induced by excessive glutamate release is well known to contribute morbidity and mortality in ischemic stroke. Over the past decades, strategies on targeting glutamate receptor did not achieve desirable clinical outcomes. Finding the downstream mechanism of the glutamate receptor activation may provide new targets to suppress the cell death. Previously, our study demonstrated that the increase of H3K4 trimethylation (H3K4me3) played a key detrimental role on neuronal necrosis; however, the mechanism of this histone modification is unclear. Through a genome-wide small RNA sequencing, we identified several tRNA-derived fragments (tRFs) and piwi-interacting RNA (piRNAs) species were enriched in glutamate-induced neuronal necrosis in rat primary neuron cultures, and this enrichment was dependent on the H3K4me3 increase. Strikingly, when we transfected several synthesized tRFs and piRNA species into neurons, the tRFs but not the piRNAs induced neuron swelling and death. The cell death morphology recapitulated neuronal necrosis induced by glutamate. For the cytotoxic effect of tRFs, our data suggested that protein synthesis was inhibited likely through induction of ribosomal stalling. By proteomic analysis of tRFs effect, the most affected pathway was enriched in the mitochondrial metabolism. Consistently, mitochondrial fragmentation was increased in neuronal necrosis, and suppression of mitochondrial fission by genetic manipulation or drug rescued neuronal necrosis. Using our previously established Drosophila model of neuronal necrosis, we found that inhibition of small RNA transcription, blocking RNA transport from nucleus to cytosol, or knocking down Ago1/2 to suppress the RNA interference effect, all rescued the fly death, suggesting transcription and processing of small RNAs contribute to neuronal necrosis. Together, these results indicate that the abnormal transcription of tRFs may play a key role downstream of the H3K4me3 increase. This provides a potential new strategy to suppress neuronal necrosis.

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

scholarly journals Disinhibitory recruitment of NMDA receptor pathways in retina

2014 ◽  
Vol 112 (1) ◽  
pp. 193-203 ◽  
Author(s):  
Santhosh Sethuramanujam ◽  
Malcolm M. Slaughter
Keyword(s):  
Nmda Receptor ◽  
Glutamate Receptors ◽  
Presynaptic Inhibition ◽  
Amacrine Cell ◽  
Glutamate Release ◽  
Relative Strength ◽  
Bipolar Cells ◽  
Ionotropic Glutamate Receptors ◽  
Nmdar Activation ◽  
On And Off Pathways

Glutamate release at bipolar to ganglion cell synapses activates NMDA and AMPA/kainic acid (KA) ionotropic glutamate receptors. Their relative strength determines the output signals of the retina. We found that this balance is tightly regulated by presynaptic inhibition that preferentially suppresses NMDA receptor (NMDAR) activation. In transient ON-OFF neurons, block of GABA and glycine feedback enhanced total NMDAR charge by 35-fold in the ON response and 9-fold in the OFF compared with a 1.7-fold enhancement of AMPA/KA receptors. Blocking only glycine receptors enhanced the NMDAR excitatory postsynaptic current 10-fold in the ON and 2-fold in the OFF pathway. Blocking GABAA or GABAC receptors (GABACRs or GABAARs) produced small changes in total NMDAR charge. When both GABAARs and GABACRs were blocked, the total NMDAR charge increased ninefold in the ON and fivefold in the OFF pathway. This exposed a strong GABACR feedback to bipolar cells that was suppressed by serial amacrine cell synapses mediated by GABAARs. The results indicate that NMDAR currents are large but latent, held in check by dual GABA and glycine presynaptic inhibition. One example of this controlled NMDAR activation is the cross talk between ON and OFF pathways. Blocking the ON pathway increased NMDAR relative strength in the OFF pathway. Stimulus prolongation similarly increased the NMDAR relative strength in the OFF response. This NMDAR enhancement was produced by a diminution in GABA and glycine feedback. Thus the retinal network recruits NMDAR pathways through presynaptic disinhibition.

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