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.

scholarly journals Metabotropic Glutamate Receptors in the Lateral Superior Olive Activate TRP-Like Channels: Age- and Experience-Dependent Regulation

2007 ◽  
Vol 97 (5) ◽  
pp. 3365-3375 ◽  
Author(s):  
F. Aura Ene ◽  
Abigail Kalmbach ◽  
Karl Kandler
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Trp Channels ◽  
Calcium Influx ◽  
Extracellular Calcium ◽  
Lateral Superior Olive ◽  
Superior Olive ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Auditory Nucleus

The lateral superior olive (LSO) is the primary auditory nucleus for processing of interaural sound level differences, which is one of the major cues for sound localization. During development, survival and maturation of LSO neurons critically depend on synaptic activity and intracellular calcium signaling. Before hearing onset, glutamatergic synaptic inputs from the cochlear nucleus (CN) to the LSO activate group I metabotropic glutamate receptors (mGluRs), which leads to calcium release from intracellular stores and large calcium influx from the extracellular milieu. Here, we investigated the nature of the mGluR-activated membrane channel that mediates the influx of extracellular calcium. Using Fura-2 calcium imaging in brain stem slices of neonatal and juvenile mice, we found that this calcium channel is blocked by Ni2+, La3+, and 2-aminoethoxydiphenylborane (2-APB), known antagonists of transient receptor potential (TRP) channels. During postnatal development, the contribution of extracellular calcium influx to mGluR-mediated Ca2+ responses gradually decreased and was almost abolished by the end of the third postnatal week. Over this period, the contribution of Ca2+ release from internal stores remained unchanged. The developmental decrease of TRP-like channel-mediated calcium influx was significantly less in congenitally deaf waltzer mice, suggesting that early auditory experience is necessary for the normal age-dependent downregulation of functional TRP channels.

Modulation of Multiple Potassium Currents by Metabotropic Glutamate Receptors in Neurons of the Hypothalamic Supraoptic Nucleus

1997 ◽  
Vol 78 (6) ◽  
pp. 3428-3437 ◽  
Author(s):  
L. A. Schrader ◽  
J. G. Tasker
Keyword(s):  
Glutamate Receptors ◽  
Supraoptic Nucleus ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Outward Current ◽  
Magnocellular Neurons ◽  
Inward Current ◽  
Voltage Gated ◽  
Metabotropic Glutamate ◽  
Group I

Schrader, L. A. and J. G. Tasker. Modulation of multiple potassium currents by metabotropic glutamate receptors in neurons of the hypothalamic supraoptic nucleus. J. Neurophysiol. 78: 3428–3437, 1997. We studied the effects of activation of the metabotropic glutamate receptors on intrinsic currents of magnocellular neurons of the supraoptic nucleus (SON) with whole cell patch-clamp and conventional intracellular recordings in coronal slices (400 μm) of the rat hypothalamus. Trans-(±)-1-amino-1,3-cyclopentane dicarboxylic acid ( trans-ACPD, 10–100 μM), a broad-spectrum metabotropic glutamate receptor agonist, evoked an inward current (18.7 ± 3.45 pA) or a slow depolarization (7.35 ± 4.73 mV) and a 10–30% decrease in whole cell conductance in ∼50% of the magnocellular neurons recorded at resting membrane potential. The decrease in conductance and the inward current were caused largely by the attenuation of a resting potassium conductance because they were reduced by the replacement of intracellular potassium with an equimolar concentration of cesium or by the addition of potassium channel blockers to the extracellular medium. In some cells, trans-ACPD still elicited a small inward current after blockade of potassium currents, which was abolished by the calcium channel blocker, CdCl2. Trans-ACPD also reduced voltage-gated and Ca2+-activated K+ currents in these cells. Trans-ACPD reduced the transient outward current ( I A) by 20–70% and/or the I A-mediated delay to spike generation in ∼60% of magnocellular neurons tested. The cells that showed a reduction of I A generally also showed a 20–60% reduction in a voltage-gated, sustained outward current. Finally, trans-ACPD attenuated the Ca2+-dependent outward current responsible for the afterhyperpolarization ( I AHP) in ∼60% of cells tested. This often revealed an underlying inward current thought to be responsible for the depolarizing afterpotential seen in some magnocellular neurons. (RS)-3,5-dihydroxyphenylglycine, a group I receptor-selective agonist, mimicked the effects of trans-ACPD on the resting and voltage-gated K+ currents. (RS)-α-methyl-4-carboxyphenylglycine, a group I/II metabotropic glutamate receptor antagonist, blocked these effects. A group II receptor agonist, 2S,1′S,2′S-2carboxycyclopropylglycine and a group III receptor agonist, l(+)-2-amino-4-phosphonobutyric acid, had no effect on the resting or voltage-gated K+ currents, indicating that the reduction of K+ currents was mediated by group I receptors. About 80% of the SON cells that were labeled immunohistochemically for vasopressin responded to metabotropic glutamate receptor activation, whereas only 33% of labeled oxytocin cells responded, suggesting that metabotropic receptors are expressed preferentially in vasopressinergic neurons. These data indicate that activation of the group I metabotropic glutamate receptors leads to an increase in the postsynaptic excitability of magnocellular neurons by blocking resting K+ currents as well as by reducing voltage-gated and Ca2+-activated K+ currents.

Selective Inhibition of Spontaneous But Not Ca2+-Dependent Release Machinery by Presynaptic Group II mGluRs in Rat Cerebellar Slices

2006 ◽  
Vol 96 (1) ◽  
pp. 86-96 ◽  
Author(s):  
Maike Glitsch
Keyword(s):  
Action Potential ◽  
Glutamate Receptors ◽  
Neurotransmitter Release ◽  
Metabotropic Glutamate Receptors ◽  
Gaba Release ◽  
Spontaneous Release ◽  
Metabotropic Receptors ◽  
Voltage Gated ◽  
Metabotropic Glutamate ◽  
Group Ii

Two main forms of neurotransmitter release are known: action potential-evoked and spontaneous release. Action potential-evoked release depends on Ca2+entry through voltage-gated Ca2+channels, whereas spontaneous release is thought to be Ca2+-independent. Generally, spontaneous and action potential-evoked release are believed to use the same release machinery to release neurotransmitter. This study shows, using the whole cell patch-clamp technique in rat cerebellar slices, that at the interneuron- Purkinje cell synapse activation of presynaptic group II metabotropic glutamate receptors suppresses spontaneous GABA release through a mechanism independent of voltage-gated Ca2+channels, store-operated Ca2+channels, and Ca2+release from intracellular Ca2+stores, suggesting that the metabotropic receptors target the release machinery directly. Voltage gated Ca2+channel-independent release following increased presynaptic cAMP production is similarly inhibited by these metabotropic receptors. In contrast, both voltage-gated Ca2+channel-dependent and presynaptic N-methyl-d-aspartate receptor-dependent GABA release were unaffected by activation of group II metabotropic glutamate receptors. Hence, the mechanisms underlying spontaneous and Ca2+-dependent GABA release are distinct in that only the former is blocked by group II metabotropic glutamate receptors. Thus the same neurotransmitter, glutamate, can activate or inhibit neurotransmitter release by selecting different receptors that target different release machineries.

Evidence for Functional Metabotropic Glutamate Receptors in the Dorsal Cochlear Nucleus

1997 ◽  
Vol 77 (4) ◽  
pp. 1889-1905 ◽  
Author(s):  
Scott C. Molitor ◽  
Paul B. Manis
Keyword(s):  
Synaptic Transmission ◽  
Dicarboxylic Acid ◽  
Glutamate Receptors ◽  
Cochlear Nucleus ◽  
Metabotropic Glutamate Receptors ◽  
Dorsal Cochlear Nucleus ◽  
Evoked Responses ◽  
Field Potentials ◽  
Metabotropic Glutamate ◽  
Field Response

Molitor, Scott C. and Paul B. Manis. Evidence for functional metabotropic glutamate receptors in the dorsal cochlear nucleus. J. Neurophysiol. 77: 1889–1905, 1997. The parallel fibers (PFs) of the dorsal cochlear nucleus (DCN) molecular layer use glutamate as a neurotransmitter. Although metabotropic glutamate receptors (mGluRs) have been identified on cells postsynaptic to the PFs, little is known about the effects of mGluR activation in PF synaptic transmission in the DCN. To investigate these effects, PF-evoked field potentials were recorded from the DCN in guinea pig brain stem slice preparations. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated components of the field response were reversibly depressed by bathing the slice in the mGluR agonists (±)-aminocyclopentane-1,3-dicarboxylic acid (trans-ACPD) or (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD]. A similar depression was produced by the mGluR1/5 agonist (RS)-3,5-dihydroxyphenylglycine, but not by the mGluR2/3 agonist (2S,1′S,2′S)-2-(carboxycyclopropyl)glycine or by the mGluR4/6/7/8 agonist l(+)-2-amino-4-phosphonobutyric acid. In addition to the AMPA component, an N-methyl-d-aspartate (NMDA) receptor-dependent component of the field potentials could be identified when the slices were bathed in a low magnesium solution. Under these conditions, the ACPD-induced depression of the AMPA component did not completely recover, whereas the depression of the NMDA component usually recovered and potentiated in some slices. Intracellular recordings of PF-evoked responses were obtained to ascertain which neuronal populations were affected by mGluR activation. Activation of mGluRs produced a reversible depression of PF-evoked responses in cartwheel cells that was not accompanied by any changes in paired-pulse facilitation. The PF-evoked responses recorded from pyramidal cells were unaffected by mGluR activation. Both cell types exhibited a reversible depolarization during (1S,3R)-ACPD application. Subsequent experiments explored the involvement of protein kinases in mediating the effects of mGluRs. The protein kinase C (PKC) activator phorbol-12,13-diacetate partially inhibited the mGluR-mediated depression of the field response;however, the PKC inhibitor 2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)-maleimide or the protein kinaseA inhibitor N-[2-(( p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide had little effect on the actions of (1S,3R)-ACPD. These results demonstrate that functional mGluRs are present at PF synapses and are capable of modulating PF synaptic transmission in the DCN.

scholarly journals Inhibitory Effect of Somatostatin-14 on L-Type Voltage-Gated Calcium Channels in Cultured Cone Photoreceptors Requires Intracellular Calcium

2009 ◽  
Vol 102 (3) ◽  
pp. 1801-1810 ◽  
Author(s):  
Kuihuan Jian ◽  
Rola Barhoumi ◽  
Michael L. Ko ◽  
Gladys Y.-P. Ko
Keyword(s):  
Calcium Channels ◽  
Intracellular Calcium ◽  
G Protein ◽  
Inhibitory Effect ◽  
Calcium Stores ◽  
Dependent Effect ◽  
Voltage Gated ◽  
Circadian Phase ◽  
Voltage Gated Calcium Channels ◽  
Somatostatin 14

The inhibitory effects of somatostatin have been well documented for many physiological processes. The action of somatostatin is through G-protein-coupled receptor-mediated second-messenger signaling, which in turn affects other downstream targets including ion channels. In the retina, somatostatin is released from a specific class of amacrine cells. Here we report that there was a circadian phase-dependent effect of somatostatin-14 (SS14) on the L-type voltage-gated calcium channels (L-VGCCs) in cultured chicken cone photoreceptors, and our study reveals that this process is dependent on intracellular calcium stores. Application of 500 nM SS14 for 2 h caused a decrease in L-VGCC currents only during the subjective night but not the subjective day. We then explored the cellular mechanisms underlying the circadian phase-dependent effect of SS14. The inhibitory effect of SS14 on L-VGCCs was mediated through the pertussis-toxin-sensitive G-protein-dependent somatostatin receptor 2 (sst2). Activation of sst2 by SS14 further activated downstream signaling involving phospholipase C and intracellular calcium stores. Mobilization of intracellular Ca2+ was required for somatostatin induced inhibition of photoreceptor L-VGCCs, suggesting that somatostatin plays an important role in the modulation of photoreceptor physiology.

scholarly journals Modulation of Pineal Melatonin Synthesis by Glutamate Involves Paracrine Interactions between Pinealocytes and Astrocytes through NF-κB Activation

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Darine Villela ◽  
Victoria Fairbanks Atherino ◽  
Larissa de Sá Lima ◽  
Anderson Augusto Moutinho ◽  
Fernanda Gaspar do Amaral ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Calcium Content ◽  
Cell Types ◽  
Inhibitory Effect ◽  
Metabotropic Glutamate ◽  
Melatonin Synthesis ◽  
Group I ◽  
Glutamatergic Signaling

The glutamatergic modulation of melatonin synthesis is well known, along with the importance of astrocytes in mediating glutamatergic signaling in the central nervous system. Pinealocytes and astrocytes are the main cell types in the pineal gland. The objective of this work was to investigate the interactions between astrocytes and pinealocytes as a part of the glutamate inhibitory effect on melatonin synthesis. Rat pinealocytes isolated or in coculture with astrocytes were incubated with glutamate in the presence of norepinephrine, and the melatonin content, was quantified. The expression of glutamate receptors, the intracellular calcium content and the NF-κB activation were analyzed in astrocytes and pinealocytes. TNF-α's possible mediation of the effect of glutamate was also investigated. The results showed that glutamate's inhibitory effect on melatonin synthesis involves interactions between astrocytes and pinealocytes, possibly through the release of TNF-α. Moreover, the activation of the astrocytic NF-κB seems to be a necessary step. In astrocytes and pinealocytes, AMPA, NMDA, and group I metabotropic glutamate receptors were observed, as well as the intracellular calcium elevation. In conclusion, there is evidence that the modulation of melatonin synthesis by glutamate involves paracrine interactions between pinealocytes and astrocytes through the activation of the astrocytic NF-κB transcription factor and possibly by subsequent TNF-αrelease.

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