Distribution of glutamate receptor subtypes in the vertebrate retina
ABSTRACT The distribution of glutamate receptor subunit/subtypes in the vertebrate retina was investigated by immunocytochemistry using anti-peptide antibodies against AMPA (GluR1-4), kainate (GluR6/7) and metabotropic (mGluR1 alpha) receptors. All receptor subtypes examined are present in the mammalian retina, but they are distributed differentially. GluR1 is present in the inner plexiform layer as well as amacrine and ganglion cell bodies. GluR2 is present mainly in the outer plexiform layer and bipolar cells. An anti-GluR2/3 antibody labels both plexiform layers and various cell bodies in the inner nuclear layer and the ganglion cell layer. GluR4 is present on Müller glial cells. In the goldfish retina, GluR2 immunoreactivity is prominent in the Mb type of ON-bipolar cells, including the dendrites and the large synaptic terminal. The putative dendritic localization is surprising, because no depolarizing conductance increase induced by glutamate is thought to be present in these cells. An AMPA receptor at a presynaptic terminal is also unusual, and probably provides feedback control of glutamate release. GluR6/7 is most widespread in the retina, being present in horizontal, bipolar, amacrine and ganglion cells. Ion channels composed of GluR6 are now known to be phosphorylated by protein kinase A, resulting in current potentiation. This property and our present observation together suggest that the glutamate receptors previously studied electrophysiologically by others in horizontal cells may contain GluR6. mGluR1 alpha is found mostly in the inner plexiform layer; its localization partially overlaps with that of the inositol trisphosphate receptor in the retina. Our results suggest that, in the retina, glutamate receptor subtypes may be expressed in selective cell types according to their specific functions.
- SourceAvailable from: Ralph J Jensen
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- "Immunostaining and electron microscopic studies in the rat retina have shown that mGlu1 receptors are present in the dendrites of rod bipolar cells and in amacrine cell processes postsynaptic to axon terminals of OFF-cone, ON-cone and rod bipolar cells . From their material they were not able to say whether ganglion cell dendrites were also labeled for mGlu1 receptors, although in an earlier study  a few large ganglion cell bodies in the rat retina were found to be immunostained for mGlu1 receptors. In the cat retina , the immunostaining pattern for mGlu1 receptors is similar to what Koulen et al.  observed in the rat retina, with two notable exceptions: 1) the synaptic terminals of rod photoreceptors but not the dendrites of rod bipolar cells were labeled, and 2) no labeling of amacrine cell processes postsynaptic to axon terminals of rod bipolar cells were observed. "
ABSTRACT: Retinitis pigmentosa (RP) is a progressive retinal degenerative disease that causes deterioration of rod and cone photoreceptors. A well-studied animal model of RP is the transgenic P23H rat, which carries a mutation in the rhodopsin gene. Previously, I reported that blocking retinal GABAC receptors in the P23H rat increases light responsiveness of retinal ganglion cells (RGCs). Because activation of metabotropic glutamate 1 (mGlu1) receptors may enhance the release of GABA onto GABAC receptors, I examined the possibility that blocking retinal mGlu1 receptors might in itself increase light responsiveness of RGCs in the P23H rat. Electrical recordings were made from RGCs in isolated P23H rat retinas. Spike activity of RGCs was measured in response to brief flashes of light over a range of light intensities. Intensity-response curves were evaluated prior to and during bath application of the mGlu1 receptor antagonist JNJ16259685. I found that JNJ16259685 increased light sensitivity of all ON-center RGCs and most OFF-center RGCs studied. RGCs that were least sensitive to light showed the greatest JNJ16259685-induced increase in light sensitivity. On average, light sensitivity increased in ON-center RGCs by 0.58 log unit and in OFF-center RGCs by 0.13 log unit. JNJ16259685 increased the maximum peak response of ON-center RGCs by 7% but had no significant effect on the maximum peak response of OFF-center RGCs. The effects of JNJ16259685 on ON-center RGCs were occluded by a GABAC receptor antagonist. The results of this study indicate that blocking retinal mGlu1 receptors in a rodent model of human RP potentiates transmission of any, weak signals originating from photoreceptors. This augmentation of photoreceptor-mediated signals to RGCs occurs presumably through a reduction in GABAC-mediated inhibition.PLoS ONE 10/2013; 8(10):e79126. DOI:10.1371/journal.pone.0079126 · 3.23 Impact Factor
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- "reno et al . , 1998 ; Watabe et al . , 2002 ; White et al . , 2003 ) . Direct ultrastructural evidence of mGluR 1 on presynaptic retinogeniculate terminals is lacking , but these cells are positive for mGluR 1 , however it is not clear whether the receptors are only within the dendritic arbor and not in axonal terminals ( Hartveit et al . , 1995 ; Peng et al . , 1995 ; Tehrani et al . , 2000 ) . The mechanisms underlying the presynaptic actions of mGluRs in inhibiting glutamate release and physiological implications are unclear . It has been hypothesized that the mGluRs are coupled to inhibitory pathway where activation of mGluR 1 inhibit glutamate release following desensitization ( Rodriguez - Mor"
ABSTRACT: Thalamocortical neurons in dorsal lateral geniculate nucleus (dLGN) dynamically convey visual information from retina to the neocortex. Activation of metabotropic glutamate receptors (mGluRs) exerts multiple effects on neural integration in dLGN; however, their direct influence on the primary sensory input, namely retinogeniculate afferents, is unknown. In the present study, we found that pharmacological or synaptic activation of type 1 mGluRs (mGluR(1)s) significantly depresses glutamatergic retinogeniculate excitation in rat thalamocortical neurons. Pharmacological activation of mGluR(1)s attenuates excitatory synaptic responses in thalamocortical neurons at a magnitude sufficient to decrease suprathreshold output of these neurons. The reduction in both NMDA and AMPA receptor-dependent synaptic responses results from a presynaptic reduction in glutamate release from retinogeniculate terminals. The suppression of retinogeniculate synaptic transmission and dampening of thalamocortical output was mimicked by tetanic activation of retinogeniculate afferent in a frequency-dependent manner that activated mGluR(1)s. Retinogeniculate excitatory synaptic transmission was also suppressed by the glutamate transport blocker TBOA (dl-threo-β-benzyloxyaspartic acid), suggesting that mGluR(1)s were activated by glutamate spillover. The data indicate that presynaptic mGluR(1) contributes to an activity-dependent mechanism that regulates retinogeniculate excitation and therefore plays a significant role in the thalamic gating of visual information.The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 09/2012; 32(37):12820-31. DOI:10.1523/JNEUROSCI.0687-12.2012 · 6.34 Impact Factor
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- "GluRs on horizontal cell dendrites appear to be formed primarily from the AMPAR subunits GluR2/3 and GluR4 [66-68], although there is immunohistochemical evidence for GluR6/7 kainate receptors in some species . Mean-variance analysis of glutamatergic currents evoked by the flash photolysis of caged glutamate has shown that the single-channel conductance of individual glutamate receptors in horizontal cells of 10.1 pS is similar to the conductance of AMPA receptors in heterologous expression systems and other CNS preparations . "
ABSTRACT: Vision is encoded at photoreceptor synapses by the number of released vesicles and size of the post-synaptic response. We hypothesized that elevating cytosolic glutamate could enhance quantal size by increasing glutamate in vesicles. We introduced glutamate (10-40 mM) into cone terminals through a patch pipette and recorded excitatory post-synaptic currents (EPSCs) from horizontal or OFF bipolar cells in the Ambystoma tigrinum retinal slice preparation. Elevating cytosolic glutamate in cone terminals enhanced EPSCs as well as quantal miniature EPSCs (mEPSCs). Enhancement was prevented by inhibiting vesicular glutamate transport with 1S,3R-1-aminocyclopentane-1,3-dicarboxylate in the patch pipette. A low affinity glutamate receptor antagonist, γD-glutamylglycine (1 mM), less effectively inhibited EPSCs evoked from cones loaded with glutamate than control cones indicating that release from cones with supplemental glutamate produced higher glutamate levels in the synaptic cleft. Raising presynaptic glutamate did not alter exocytotic capacitance responses and exocytosis was observed after inhibiting glutamate loading with the vesicular ATPase inhibitor, concanamycin A, suggesting that release capability is not restricted by low vesicular glutamate levels. Variance-mean analysis of currents evoked by flash photolysis of caged glutamate indicated that horizontal cell AMPA receptors have a single channel conductance of 10.1 pS suggesting that ~8.7 GluRs contribute to each mEPSC. Quantal amplitude at the cone ribbon synapse is capable of adjustment by changes in cytosolic glutamate levels. The small number of channels contributing to each mEPSC suggests that stochastic variability in channel opening could be an important source of quantal variability.Molecular vision 04/2011; 17:920-31. · 1.99 Impact Factor