Activation of group II metabotropic glutamate receptors reduces directional selectivity in retinal ganglion cells

As in many CNS neurons, retinal ganglion cells (RGCs) receive fast synaptic activation through postsynaptic ionotropic receptors. However, the potential role of postsynaptic group I metabotropic glutamate receptors (mGluRs) in these neurons is unknown. In this study we first demonstrated that the selective group I mGluR agonist ( S)-3,5-dihydroxyphenylglycine (DHPG) increased intracellular calcium concentration in neurons within the ganglion cell layer of the rat retina. This prompted us to use an immunopanned-RGC and cortical astroglia coculture preparation to explore the effect of group I mGluR activation on the electrophysiological properties of cultured RGCs. Using perforated patch-clamp recordings in current-clamp configuration, we found that application of DHPG increased spontaneous spiking and depolarized the resting membrane potential of RGCs. This boosting effect was attributed to an increase in membrane resistance due to blockade of a background K+ conductance. Further experiments showed that the group I mGluR-sensitive K+ conductance was not blocked by 3 mM Cs+, but was sensitive to acidification. Pharmacological studies indicated that the effect of DHPG on RGCs was mediated by the mGluR1 rather than the mGluR5 receptor subtype. Our results suggest a facilitatory role for group I mGluR activation in modulating RGC excitability in the mammalian inner retina.

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Activation of group I metabotropic glutamate receptors regulates the excitability of rat retinal ganglion cells by suppressing Kir and I h

Brain Structure and Function ◽

10.1007/s00429-016-1248-3 ◽

2016 ◽

Vol 222 (2) ◽

pp. 813-830 ◽

Cited By ~ 12

Author(s):

Qian Li ◽

Peng Cui ◽

Yanying Miao ◽

Feng Gao ◽

Xue-Yan Li ◽

...

Keyword(s):

Glutamate Receptors ◽

Retinal Ganglion Cells ◽

Metabotropic Glutamate Receptors ◽

Ganglion Cells ◽

Retinal Ganglion ◽

Metabotropic Glutamate ◽

Group I

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Modulation of metabotropic glutamate receptors fails to prevent the loss of adult rat retinal ganglion cells following axotomy or N-methyl-d-aspartate lesion in vivo

Neuroscience Letters ◽

10.1016/s0304-3940(01)02318-7 ◽

2001 ◽

Vol 315 (3) ◽

pp. 117-120 ◽

Cited By ~ 7

Author(s):

Pawel Kermer ◽

Nikolaj Klöcker ◽

Mathias Bähr

Keyword(s):

Glutamate Receptors ◽

Retinal Ganglion Cells ◽

Metabotropic Glutamate Receptors ◽

Ganglion Cells ◽

Retinal Ganglion ◽

Metabotropic Glutamate ◽

Adult Rat

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

Journal of Neurophysiology ◽

10.1152/jn.00897.2012 ◽

2013 ◽

Vol 109 (1) ◽

pp. 113-123 ◽

Cited By ~ 9

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.

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

Journal of Neurophysiology ◽

10.1152/jn.1999.82.6.2947 ◽

1999 ◽

Vol 82 (6) ◽

pp. 2947-2955 ◽

Cited By ~ 28

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.

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