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.

2009 ◽  
Vol 87 (10) ◽  
pp. 883-891 ◽  
Author(s):  
Jason Schapansky ◽  
Marc Morissette ◽  
Gary Odero ◽  
Benedict Albensi ◽  
Gordon Glazner
Keyword(s):  
Endoplasmic Reticulum ◽  
Intracellular Calcium ◽  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Calcium Release ◽  
Ryanodine Receptors ◽  
Intracellular Free Calcium ◽  
Free Calcium ◽  
Metabotropic Glutamate

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.

Activation of metabotropic glutamate receptors induces long-term depression of GABAergic inhibition in hippocampus

1993 ◽  
Vol 69 (3) ◽  
pp. 1000-1004 ◽  
Author(s):  
Y. B. Liu ◽  
J. F. Disterhoft ◽  
N. T. Slater
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Hippocampal Slices ◽  
Input Resistance ◽  
Nmda Receptor Antagonist ◽  
Metabotropic Glutamate ◽  
Epileptiform Discharges ◽  
Bath Application

1. The long-term enhancement of synaptic excitability in CA1 hippocampal pyramidal neurons produced by activation of metabotropic glutamate receptors (mGluRs) was studied in rabbit hippocampal slices in vitro. 2. Bath application of the mGluR agonist (1S,3R)-1-aminocyclopentane-1,3- dicarboxylic acid (1S,3R-ACPD) (5-20 microM) for 20 min produced a reversible depolarization of membrane potentiatil, blockade of spike accommodation, and increase in input resistance of CA1 neurons. However, a long-lasting increase in synaptic excitability was observed: single stimuli applied to the Schaffer collateral commisural fiber pathway evoked epileptiform discharges in the presence of 1S,3R-ACPD and after the washout of 1S,3R-ACPD, persistent paroxysmal depolarization shifts (PDSs) were evoked by afferent stimulation. A long-lasting enhancement of synaptic excitability was also observed in the presence of the NMDA receptor antagonist D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5), which blocked the stimulation-evoked PDS and associated afterdischarges. 3. When biphasic, monosynaptically evoked inhibitory post-synaptic potentials (IPSPs) were recorded in the presence of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10–15 microM) and D-AP5 (20 microM), the bath application of 1S,3R-ACPD produced a significant reduction (approximately 50%) of both components of the IPSP, which persisted after the washout of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Glutamatergic Calcium Responses in the Developing Lateral Superior Olive: Receptor Types and Their Specific Activation by Synaptic Activity Patterns

2003 ◽  
Vol 90 (4) ◽  
pp. 2581-2591 ◽  
Author(s):  
F. Aura Ene ◽  
Paul H. M. Kullmann ◽  
Deda C. Gillespie ◽  
Karl Kandler
Keyword(s):  
Calcium Channels ◽  
Intracellular Calcium ◽  
Glutamate Receptors ◽  
Cochlear Nucleus ◽  
Metabotropic Glutamate Receptors ◽  
Lateral Superior Olive ◽  
Voltage Gated ◽  
Superior Olive ◽  
Metabotropic Glutamate ◽  
Voltage Gated Calcium Channels

The lateral superior olive (LSO) is a binaural auditory brain stem nucleus that plays a central role in sound localization. Survival and maturation of developing LSO neurons critically depend on intracellular calcium signaling. Here we investigated the mechanisms by which glutamatergic afferents from the cochlear nucleus increase intracellular calcium concentration in LSO neurons. Using fura-2 calcium imaging in slices prepared from neonatal mice, we found that cochlear nucleus afferents can activate all major classes of ionotropic and metabotropic glutamate receptors, each of which contributes to an increase in intracellular calcium. The specific activation of different glutamate receptor classes was dependent on response amplitudes and afferent stimulus patterns. Low-amplitude responses elicited by single stimuli were entirely mediated by calcium-impermeable AMPA/kainate receptors that activated voltage-gated calcium channels. Larger-amplitude responses elicited by either single stimuli or stimulus trains resulted in additional calcium influx through N-methyl-d-aspartate receptors. Finally, high-frequency stimulation also recruited group I and group II metabotropic glutamate receptors, both of which mobilized intracellular calcium. This calcium release in turn activated a strong influx of extracellular calcium through a membrane calcium channel that is distinct from voltage-gated calcium channels. Together, these results indicate that before hearing onset, distinct patterns of afferent activity generate qualitatively distinct types of calcium responses, which likely serve in guiding different aspects of LSO development.

Persistent current oscillations produced by activation of metabotropic glutamate receptors in immature rat CA3 hippocampal neurons

1995 ◽  
Vol 73 (4) ◽  
pp. 1422-1429 ◽  
Author(s):  
L. Aniksztejn ◽  
M. Sciancalepore ◽  
Y. Ben Ari ◽  
E. Cherubini
Keyword(s):  
Glutamate Receptors ◽  
Hippocampal Neurons ◽  
Metabotropic Glutamate Receptors ◽  
Calcium Release ◽  
Release Process ◽  
Metabotropic Glutamate ◽  
Voltage Dependent ◽  
Inward Currents ◽  
Presynaptic Nerve Terminals ◽  
Calcium Induced Calcium Release

1. The single-electrode voltage-clamp technique was used to study the effects of the metabotropic glutamate receptors (mGluRs) agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD, ACPD, 3-10 microM) on CA3 hippocampal neurons during the 1st 10 days of postnatal (P) life and in adulthood. 2. Repeated applications of 1S,3R-ACPD, in the presence of tetrodotoxin (TTX, 1 microM), tetraethylammonium chloride (TEACl 10 mM), and CsCl (2 mM), induced in immature but not in adult neurons periodic inward currents (PICs) that persisted for several hours after the last application of the agonist. 3. PICs, which were generated by nonspecific cationic currents, reversed polarity at 2.8 +/- 3 (SD) mV. They were reversibly blocked by kynurenic acid (1 mM), suggesting that they were mediated by glutamate acting on ionotropic receptors. They were also abolished in a nominally Ca(2+)-free medium. 4. PICs were irreversibly abolished by thapsigargin (10 microM) but were unaffected by ryanodine (10-40 microM). Caffeine (2 mM) also reversibly blocked PICs; this effect was independent from adenosine 3',5'-cyclic monophosphate (cAMP) accumulation, inhibition of voltage-dependent Ca2+ current, or blockade of adenosine receptors. 5. We suggest that, in neonatal slices, mGluRs-induced PICs are triggered by elevation of [Ca2+]i, after mobilization of Ca2+ from inositol 1,4,5-trisphosphate (InsP3)-sensitive stores. This will lead to a persistent, pulsatile release of glutamate from presynaptic nerve terminals, a phenomenon that is probably maintained via a calcium-induced-calcium release process.

Group 2 metabotropic glutamate receptors induced long term depression in mouse striatal slices

2001 ◽  
Vol 316 (3) ◽  
pp. 178-182 ◽  
Author(s):  
Laetitia Kahn ◽  
Gérard Alonso ◽  
David Robbe ◽  
Joël Bockaert ◽  
Olivier J. Manzoni
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Long Term Depression ◽  
Striatal Slices ◽  
Metabotropic Glutamate ◽  
Group 2
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