Heterogeneous distribution of AMPA glutamate receptor subunits at the photoreceptor synapses of rodent retina

Hack, Iris; Frech, Moritz J.; Dick, Oliver; Peichl, Leo; Brandstätter, Johann Helmut

doi:10.1111/j.1460-9568.2001.01357.x

Cited by 85 publications

(121 citation statements)

References 48 publications

(70 reference statements)

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“…Since horizontal cells not only regulate glutamate release via feedback but also contribute to glutamate binding by ionotropic glutamate receptors (Hack et al, 2001) and glutamate uptake by glutamate transporters (for review, see Barnett and Bull, 2008), lack of horizontal cells may substantially increase the glutamate concentration in the synaptic cleft. Such a rise in extracellular glutamate inhibits the glutamate/cystine antiporter (Lewerenz et al, 2012) present in photoreceptors (Hu et al, 2008), which transports cystine into and glutamate out of the cell.…”

Section: Discussionmentioning

confidence: 99%

“…In wild-type retinae, GluR1 immunoreactivity formed band-like clusters below cone pedicles (Fig. 3 B, C), indicating flat contacts to OFF bipolar cells (Hack et al, 2001). In Cx57ϩ/DTR retinae, distribution of GluR1 immunosignals was less regular, though still associated with clusters of glypho-labeled cone pedicles (Fig.…”

Section: Contacts Between Cones and Off Bipolar Cells Were Retainedmentioning

confidence: 99%

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Ablation of Retinal Horizontal Cells from Adult Mice Leads to Rod Degeneration and Remodeling in the Outer Retina

Sonntag

Dedek²,

Dorgau³

et al. 2012

Journal of Neuroscience

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In the brain, including the retina, interneurons show an enormous structural and functional diversity. Retinal horizontal cells represent a class of interneurons that form triad synapses with photoreceptors and ON bipolar cells. At this first retinal synapse, horizontal cells modulate signal transmission from photoreceptors to bipolar cells by feedback and feedforward inhibition. To test how the fully developed retina reacts to the specific loss of horizontal cells, these interneurons were specifically ablated from adult mice using the diphtheria toxin (DT)/DT-receptor system and the connexin57 promoter. Following ablation, the retinal network responded with extensive remodeling: rods retracted their axons from the outer plexiform layer and partially degenerated, whereas cones survived. Cone pedicles remained in the outer plexiform layer and preserved synaptic contacts with OFF but not with ON bipolar cells. Consistently, the retinal ON pathway was impaired, leading to reduced amplitudes and prolonged latencies in electroretinograms. However, ganglion cell responses showed only slight changes in time course, presumably because ON bipolar cells formed multiple ectopic synapses with photoreceptors, and visual performance, assessed with an optomotor system, was only mildly affected. Thus, the loss of an entire interneuron class can be largely compensated even by the adult retinal network.

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Section: Discussionmentioning

confidence: 99%

Section: Contacts Between Cones and Off Bipolar Cells Were Retainedmentioning

confidence: 99%

Ablation of Retinal Horizontal Cells from Adult Mice Leads to Rod Degeneration and Remodeling in the Outer Retina

Sonntag

Dedek²,

Dorgau³

et al. 2012

Journal of Neuroscience

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“…For example, it has been shown to play a role in insulin secretion from pancreatic islet beta-cells~Spurlin et al & Vardi, 1999;Qin & Pourcho, 1999a, 1999bHack et al, 2001;Pan & Massey, 2007!, although …”

Section: Pre-or Postsynaptic Function?mentioning

confidence: 99%

Robust syntaxin-4 immunoreactivity in mammalian horizontal cell processes

et al. 2007

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Horizontal cells mediate inhibitory feed-forward and feedback communication in the outer retina; however, mechanisms that underlie transmitter release from mammalian horizontal cells are poorly understood. Toward determining whether the molecular machinery for exocytosis is present in horizontal cells, we investigated the localization of syntaxin-4, a SNARE protein involved in targeting vesicles to the plasma membrane, in mouse, rat, and rabbit retinae using immunocytochemistry. We report robust expression of syntaxin-4 in the outer plexiform layer of all three species. Syntaxin-4 occurred in processes and tips of horizontal cells, with regularly spaced, thicker sandwich-like structures along the processes. Double labeling with syntaxin-4 and calbindin antibodies, a horizontal cell marker, demonstrated syntaxin-4 localization to horizontal cell processes; whereas, double labeling with PKC antibodies, a rod bipolar cell~RBC! marker, showed a lack of co-localization, with syntaxin-4 immunolabeling occurring just distal to RBC dendritic tips. Syntaxin-4 immunolabeling occurred within VGLUT-1-immunoreactive photoreceptor terminals and underneath synaptic ribbons, labeled by CtBP20RIBEYE antibodies, consistent with localization in invaginating horizontal cell tips at photoreceptor triad synapses. Vertical sections of retina immunostained for syntaxin-4 and peanut agglutinin~PNA! established that the prominent patches of syntaxin-4 immunoreactivity were adjacent to the base of cone pedicles. Horizontal sections through the OPL indicate a one-to-one co-localization of syntaxin-4 densities at likely all cone pedicles, with syntaxin-4 immunoreactivity interdigitating with PNA labeling. Pre-embedding immuno-electron microscopy confirmed the subcellular localization of syntaxin-4 labeling to lateral elements at both rod and cone triad synapses. Finally, co-localization with SNAP-25, a possible binding partner of syntaxin-4, indicated co-expression of these SNARE proteins in the same subcellular compartment of the horizontal cell. Taken together, the strong expression of these two SNARE proteins in the processes and endings of horizontal cells at rod and cone terminals suggests that horizontal cell axons and dendrites are likely sites of exocytotic activity.

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“…AB1506) was raised in rabbit against an affinity-purified peptide from the carboxy terminus (RQSSGLAVIASDLP). These two AMPAR antibodies have been widely used in mammalian retina including rat and characterized previously by Western blotting (recognizing a band at 100 ~ 110 kD) and immunocytochemistry (Ghosh et al, 2001;Grünert et al, 2002Grünert et al, , 2003Hack et al, 2001Hack et al, , 2002Li et al, 2002). Polyclonal goat anti-CTB (List biological Lab., Campbell, CA; Cat.…”

Section: Primary Antibodiesmentioning

confidence: 99%

Distinct perisynaptic and synaptic localization of NMDA and AMPA receptors on ganglion cells in rat retina

Zhang

Diamond

2006

J of Comparative Neurology

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At most excitatory synapses, AMPA and NMDA receptors (AMPARs and NMDARs) occupy the postsynaptic density (PSD) and contribute to miniature excitatory postsynaptic currents (mEPSCs) elicited by single transmitter quanta. Juxtaposition of AMPARs and NMDARs may be crucial for certain types of synaptic plasticity, although extrasynaptic NMDARs also may contribute. AMPARs and NMDARs also contribute to evoked EPSCs in retinal ganglion cells (RGCs), but mEPSCs are mediated solely by AMPARs. Previous work indicates that an NMDAR component emerges in mEPSCs when glutamate uptake is reduced, suggesting that NMDARs are located near the release site but perhaps not directly beneath in the PSD. Consistent with this idea, NMDARs on RGCs encounter a lower glutamate concentration during synaptic transmission than do AMPARs. To understand better the roles of NMDARs in RGC function, we have used immunohistochemical and electron microscopic techniques to determine the precise subsynaptic localization of NMDARs in RGC dendrites. RGC dendrites were labeled retrogradely with cholera toxin B subunit (CTB) injected into the superior colliculus (SC) and identified using postembedding immunogold methods. Co-labeling with antibodies directed toward AMPARs and/ or NMDARs, we found that nearly all AMPARs are located within the PSD, while most NMDARs are located perisynaptically, 100-300 nm from the PSD. This morphological evidence for exclusively perisynaptic NMDARs localizations suggests a distinct role for NMDARs in RGC function.

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Heterogeneous distribution of AMPA glutamate receptor subunits at the photoreceptor synapses of rodent retina

Cited by 85 publications

References 48 publications

Ablation of Retinal Horizontal Cells from Adult Mice Leads to Rod Degeneration and Remodeling in the Outer Retina

Ablation of Retinal Horizontal Cells from Adult Mice Leads to Rod Degeneration and Remodeling in the Outer Retina

Robust syntaxin-4 immunoreactivity in mammalian horizontal cell processes

Distinct perisynaptic and synaptic localization of NMDA and AMPA receptors on ganglion cells in rat retina

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