Activation of group II metabotropic glutamate receptors inhibits glutamate release from salamander retinal photoreceptors

2002 ◽  
Vol 19 (3) ◽  
pp. 275-281 ◽  
Author(s):  
MATTHEW H. HIGGS ◽  
PETER D. LUKASIEWICZ
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Ganglion Cells ◽  
Glutamate Release ◽  
Bipolar Cells ◽  
Horizontal Cells ◽  
Inward Current ◽  
Metabotropic Glutamate ◽  
Retinal Photoreceptors ◽  
Group Ii

We investigated the effects of group II metabotropic glutamate receptor (mGluR) activation on excitatory synaptic transmission in the salamander retinal slice preparation. The group II selective agonists DCG-IV and LY354740 reduced light-evoked excitatory postsynaptic currents (EPSCs) in ganglion cells. To determine the synaptic basis of this effect, we also recorded from bipolar cells and horizontal cells. In ON bipolar cells, DCG-IV increased the inward current in darkness but did not affect the peak current at light onset. In OFF bipolar cells and horizontal cells, DCG-IV had the opposite effect, reducing the inward current in darkness. Given the opposite polarities of these two classes of synapses, our results suggest that group II mGluRs act presynaptically to reduce glutamate release from photoreceptors. To determine whether DCG-IV affected rods or cones, we applied light stimuli that selectively activate each type of photoreceptor. In horizontal cells, most of which receive mixed synaptic input from rods and cones, DCG-IV reduced rod-driven EPSCs evoked by 470-nm stimuli and cone-driven EPSCs elicited by 700-nm stimuli in the presence of a rod-saturating background. Thus, activation of group II mGluRs reduced rod- and cone-mediated glutamate release. Our results suggest that group II mGluRs could mediate feedback by which extracellular glutamate inhibits glutamate release from photoreceptor terminals.

scholarly journals Metabotropic glutamate receptors and glutamate transporters shape transmission at the developing retinogeniculate synapse

2013 ◽  
Vol 109 (1) ◽  
pp. 113-123 ◽  
Author(s):  
Jessica L. Hauser ◽  
Eleanore B. Edson ◽  
Bryan M. Hooks ◽  
Chinfei Chen
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Time Course ◽  
Ganglion Cells ◽  
Glutamate Transporters ◽  
Decay Kinetics ◽  
Metabotropic Glutamate ◽  
Glutamate Concentration ◽  
Group Ii ◽  
Retinogeniculate Synapse

Over the first few postnatal weeks, extensive remodeling occurs at the developing murine retinogeniculate synapse, the connection between retinal ganglion cells (RGCs) and the visual thalamus. Although numerous studies have described the role of activity in the refinement of this connection, little is known about the mechanisms that regulate glutamate concentration at and around the synapse over development. Here we show that interactions between glutamate transporters and metabotropic glutamate receptors (mGluRs) dynamically control the peak and time course of the excitatory postsynaptic current (EPSC) at the immature synapse. Inhibiting glutamate transporters by bath application of TBOA (dl- threo-β-benzyloxyaspartic acid) prolonged the decay kinetics of both α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and N-methyl-d-aspartate receptor (NMDAR) currents at all ages. Moreover, at the immature synapse, TBOA-induced increases in glutamate concentration led to the activation of group II/III mGluRs and a subsequent reduction in neurotransmitter release at RGC terminals. Inhibition of this negative-feedback mechanism resulted in a small but significant increase in peak NMDAR EPSCs during basal stimulation and a substantial increase in the peak with coapplication of TBOA. Activation of mGluRs also shaped the synaptic response during high-frequency trains of stimulation that mimic spontaneous RGC activity. At the mature synapse, however, the group II mGluRs and the group III mGluR7-mediated response are downregulated. Our results suggest that transporters reduce spillover of glutamate, shielding NMDARs and mGluRs from the neurotransmitter. Furthermore, mechanisms of glutamate clearance and release interact dynamically to control the glutamate transient at the developing retinogeniculate synapse.

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.

Different types of synapses with different spectral types of cones underlie color opponency in a bipolar cell of the turtle retina

1999 ◽  
Vol 16 (5) ◽  
pp. 801-809 ◽  
Author(s):  
SILKE HAVERKAMP ◽  
WOLFGANG MÖCKEL ◽  
JOSEF AMMERMÜLLER
Keyword(s):  
Bipolar Cell ◽  
Metabotropic Glutamate Receptors ◽  
Horizontal Cell ◽  
Bipolar Cells ◽  
Horizontal Cells ◽  
Color Processing ◽  
Ionotropic Receptors ◽  
Metabotropic Glutamate ◽  
Different Types ◽  
Color Opponency

Electrophysiologically, color-opponent retinal bipolar cells respond with opposite polarities to stimulation with different wavelengths of light. The origin of these different polarities in the same bipolar cell has always been a mystery. Here we show that an intracellularly recorded and HRP-injected, red-ON, blue/green-OFF bipolar cell of the turtle retina made invaginating (ribbon associated) synapses exclusively with L-cones. Non-invaginating synapses resembling wide-cleft basal junctions were made exclusively with M-cones. Input from S-cones was not seen. From these results we suggest sign-inverting transmission from L-cones at invaginating synapses via metabotropic glutamate receptors, and sign-conserving transmission from M-cones at wide-cleft basal junctions via ionotropic receptors. To explain the pronounced blue sensitivity of the bipolar cell, computer simulations were performed using a sign-conserving input from a yellow/blue chromaticity-type (H3) horizontal cell. The response properties of the red-ON, blue/green-OFF bipolar cell could be quantitatively reproduced by this means. The simulation also explained the asymmetry in L- and M-cone inputs to the bipolar cell as found in the ultrastructural analysis and assigned a putative role to H3 horizontal cells in color processing in the turtle retina.

Roles of specific metabotropic glutamate receptor subtypes in regulation of hippocampal CA1 pyramidal cell excitability

1995 ◽  
Vol 74 (1) ◽  
pp. 122-129 ◽  
Author(s):  
R. W. Gereau ◽  
P. J. Conn
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Brain Slices ◽  
Second Messenger ◽  
Receptor Subtypes ◽  
Bhk Cells ◽  
Group Iii ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Group Ii

1. Metabotropic glutamate receptors (mGluRs) are coupled to various second-messenger systems through guanosine 5'-triphosphate-binding proteins. To date, at least seven mGluRs have been cloned, and these mGluR subtypes can be divided into three major groups on the basis of similarities in amino acid sequence, coupling to second-messenger cascades in expression systems, and pharmacological profiles. These groups include group I (mGluR1 and mGluR5), group II (mGluR2 and mGluR3), and group III (mGluR4, mGluR6, and mGluR7). 2. On the basis of its selective activation of phosphoinositide hydrolysis in brain slices and its ability to activate mGluR1a expressed in Xenopus oocytes, others have suggested that 3.5-dihydroxyphenylglycine (DHPG) may be selective for group I mGluRs. Consistent with this hypothesis, we report that DHPG also activates mGluR5 expressed in oocytes, whereas it is inactive at mGluR4 and mGluR7 expressed in baby hamster kidney (BHK) cells. The compound (2S,1'R,2'R,3'R)-2-(2.3-dicarboxycyclopropyl)glycine (DCG-IV) activates both mGluR2 and mGluR3 at submicromolar concentrations, whereas it is inactive at mGluR4 and mGluR1, suggesting that this compound may be selective for group II mGluRs. Consistent with this hypothesis, we find that DCG-IV does not activate mGluR5 expressed in oocytes and does not activate mGluR7 expressed in BHK cells. These findings suggest that DHPG and DCG-IV are highly selective agonists for group I and group II mGluRs, respectively. 3. Previous studies that have examined the physiological roles of mGluRs have generally used agonists that do not differentiate between the various subtypes.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals LRIT3 is required for nyctalopin expression and normal ON and OFF pathway signaling in the retina

2018 ◽  
Author(s):  
Nazarul Hasan ◽  
Gobinda Pangeni ◽  
Thomas A. Ray ◽  
Kathryn M. Fransen ◽  
Jennifer Noel ◽  
...  
Keyword(s):  
Visual Function ◽  
Metabotropic Glutamate Receptor ◽  
Glutamate Release ◽  
Electrode Array ◽  
Light Response ◽  
Photoreceptor Cells ◽  
Sole Source ◽  
Bipolar Cells ◽  
Metabotropic Glutamate ◽  
And Function

ABSTRACTAt its first synapse, the retina establishes two parallel channels that encode light increments (ON) or decrements (OFF). At the same synapse, changes in photoreceptor glutamate release are sensed by ON bipolar cells (BCs) via the metabotropic glutamate receptor 6 (mGluR6), and OFF BCs via ionotropic BCs, which differ in their synaptic configuration with the photoreceptor terminal. ON BCs form invaginating synapses that bring them in close proximity to presynaptic ribbons and the presumed sole source of glutamate release. OFF bipolar cells form flat contacts distal to the ribbon synapse. We investigated the role of LRIT3 in normal assembly and function of the mGlur6 signaling cascade present in ON BCs. We demonstrate that LRIT3 is required for nyctalopin expression and thus TRPM1 expression and function. Using glutamate imaging, whole-cell electrophysiology, and multi-electrode array extracellular recordings we demonstrate that the loss of LRIT3 impacts both the ON and OFF pathways at the level of the BCs. The effect on ON pathway signaling, a lack of ON BC response, is shared by mutants lacking mGluR6, TRPM1 GPR179 or nyctalopin. The effects on the OFF pathway are unique to LRIT3, and include a decrease in response amplitude of both OFF BC and GCs. Based on these results, we propose a working model where LRIT3 is required for either efficient glutamate release or reuptake from the first retinal synapse.SIGNIFICANCE STATEMENTAt the first visual synapse, photoreceptor cells signal to two distinct bipolar cell (BC) populations, one characterized by a depolarizing response to light onset (ON or DBCs), the other by a hyperpolarizing response (OFF or HBCs). The DBC light response depends on a G protein-coupled receptor and associated protein complex, known as the signalplex. Mutations in signalplex proteins lead to DBC pathway-specific loss of visual function. Here we show how loss of LRIT3, a previously identified signalplex protein, prevents functional assembly of the DBC signalplex and alters visual function in both ON and OFF signaling pathways. Thus, our results indicate that the function of LRIT3 at this first synapse extends beyond assembly of the DBC signalplex.

Adenosine A1 and Class II Metabotropic Glutamate Receptors Mediate Shared Presynaptic Inhibition of Retinotectal Transmission

1999 ◽  
Vol 82 (6) ◽  
pp. 2947-2955 ◽  
Author(s):  
Chunyi Zhang ◽  
John T. Schmidt
Keyword(s):  
Calcium Channels ◽  
Synaptic Transmission ◽  
Presynaptic Inhibition ◽  
Metabotropic Glutamate Receptors ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Metabotropic Glutamate ◽  
Adenosine A1 ◽  
A1 Adenosine Receptors ◽  
Group Ii

Presynaptic inhibition is one of the major control mechanisms in the CNS. Previously we reported that adenosine A1 receptors mediate presynaptic inhibition at the retinotectal synapse of goldfish. Here we extend these findings to metabotropic glutamate receptors (mGluRs) and report that presynaptic inhibition produced by both A1 adenosine receptors and group II mGluRs is due to Gi protein coupling to inhibition of N-type calcium channels in the retinal ganglion cells. Adenosine (100 μM) and an A1 (but not A2) receptor agonist reduced calcium current ( I Ca2+) by 16–19% in cultured retinal ganglion cells, consistent with their inhibition of retinotectal synaptic transmission (−30% amplitude of field potentials). The general metabotropic glutamate receptor (mGluR) agonist 1S,3R-1-amino-cyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD, 50 μM) and the selective group II mGluR receptor agonist (2S,2′R,3′R)-2-(2′,3′-dicarboxy-cyclopropyl)glycine (DCG-IV, 300 nM) inhibited both synaptic transmission and I Ca2+, whereas the group III mGluR agonistl-2-amino-4-phosphono-butyrate (l-AP4) inhibited neither synaptic transmission nor I Ca2+. When the N-type calcium channels were blocked with ω-conotoxin GVIA, both adenosine and DCG-IV had much smaller percentage effects on the residual 20% of I Ca2+, suggesting effects mainly on the N-type calcium channels. The inhibitory effects of A1 adenosine receptors and mGluRs were both blocked by pertussis toxin, indicating that they are mediated by either Gi or Go. They were also inhibited by activation of protein kinase C (PKC), which is known to phosphorylate and inhibit Gi. Finally, when applied sequentially, inhibition by adenosine and DCG-IV were not additive but occluded each other. Together these results suggest that adenosine A1 receptors and group II mGluRs mediate presynaptic inhibition of retinotectal synaptic transmission by sharing a pertussis toxin (PTX)–sensitive, PKC-regulated Gi protein coupled to N-type calcium channels.

Metabotropic Glutamate Receptors in Median Preoptic Neurons Modulate Neuronal Excitability and Glutamatergic and GABAergic Inputs From the Subfornical Organ

2010 ◽  
Vol 103 (2) ◽  
pp. 1104-1113 ◽  
Author(s):  
Miloslav Kolaj ◽  
Leo P. Renaud
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Subfornical Organ ◽  
Lamina Terminalis ◽  
Patch Clamp Recording ◽  
Paired Pulse ◽  
Metabotropic Glutamate ◽  
Postsynaptic Currents ◽  
Group I ◽  
Group Ii

Cardiovascular and behavioral responses to circulating angiotensin require intact connectivity along the upper lamina terminalis joining the subfornical organ (SFO) with the median preoptic nucleus (MnPO). In the present study on MnPO neurons, we used whole cell patch-clamp recording techniques in brain slice preparations to evaluate the influence of metabotropic glutamate receptor (mGluR) agonists on modulating their intrinsic excitability and SFO-evoked glutamatergic and GABAergic postsynaptic currents. In 22/36 cells, bath application of a mGluR group I agonist ( S)-3,5-dihydroxyphenylglycine (DHPG) induced a TTX-resistant inward current coupled with decrease in a membrane K+ conductance but also a possible increase in a nonselective cationic conductance. By contrast, 27/49 cells responded to a mGluR group II agonist (2S,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl)glycine (DCG IV) with a TTX-resistant outward current and increase in membrane conductance that reversed around −95 mV, suggesting opening of K+ channels. None of 19 cells responded to the mGluR group III agonist l-(+)-2-amino-4-phosphonobutyric acid (l-AP4). Agonists for all mGluR groups suppressed SFO-evoked excitatory postsynaptic currents and significantly increased paired-pulse ratios, implying a presynaptic mechanism. Only the mGluR group II agonist significantly reduced SFO-evoked inhibitory postsynaptic currents and caused an increase in paired-pulse ratios. These results suggest a complexity of pre- and postsynaptic mGluRs are available to modulate rapid neurotransmission along the upper lamina terminalis from SFO to MnPO.

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