Light adaptation affects synaptic vesicle density but not the distribution of GABA
            <sub>A</sub>
            receptors in goldfish photoreceptor terminals

Yazulla, Stephen; Studholme, Keith M.

doi:10.1002/(sici)1097-0029(19970101)36:1<43::aid-jemt4>3.0.co;2-#

Cited by 18 publications

(8 citation statements)

References 61 publications

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“…CB1R-IR was not immediately apposed to the synaptic ribbon, but was at some distance from it. In this regard, the absence of CB1R-IR near the arciform density within the invagination is similar to that reported for GABA A receptors (Yazulla et al, 1989; Yazulla and Studholme, 1997), perhaps consistent with this region being the site of active vesicular release and membrane fusion due to exocytosis. Studies also agree that CB1R-IR is found on a small population of amacrine cells.…”

Section: Retinal Endocannabinoids — Content and Distributionsupporting

confidence: 87%

Endocannabinoids in the retina: From marijuana to neuroprotection

Yazulla¹

2008

Progress in Retinal and Eye Research

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148

143

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The active component of the marijuana plant Cannabis sativa, Δ 9 -tetrahydrocannabinol (THC), produces numerous beneficial effects, including analgesia, appetite stimulation and nausea reduction, in addition to its psychotropic effects. THC mimics the action of endogenous fatty acid derivatives, referred to as endocannabinoids. The effects of THC and the endocannabinoids are mediated largely by metabotropic receptors that are distributed throughout the nervous and peripheral organ systems. There is great interest in endocannabinoids for their role in neuroplasticity as well as for therapeutic use in numerous conditions, including pain, stroke, cancer, obesity, osteoporosis, fertility, neurodegenerative diseases, multiple sclerosis, glaucoma and inflammatory diseases, among others. However, there has been relatively far less research on this topic in the eye and retina compared with the brain and other organ systems. The purpose of this review is to introduce the "cannabinergic" field to the retinal community. All of the fundamental work on cannabinoids has been performed in non-retinal preparations, necessitating extensive dependence on this literature for background. Happily, the retinal cannabinoid system has much in common with other regions of the central nervous system. For example, there is general agreement that cannabinoids suppress dopamine release and presynaptically reduce transmitter release from cones and bipolar cells. How these effects relate to light and dark adaptation, receptive field formation, temporal properties of ganglion cells or visual perception are unknown. The presence of multiple endocannabinoids, degradative enzymes with their bioactive metabolites, and receptors provides a broad spectrum of opportunities for basic research and to identify targets for therapeutic application to retinal diseases.

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Section: Retinal Endocannabinoids — Content and Distributionsupporting

confidence: 87%

Endocannabinoids in the retina: From marijuana to neuroprotection

Yazulla¹

2008

Progress in Retinal and Eye Research

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148

143

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“…With regard to goldfish, only β2/β3 subunits had been previously localized to cone pedicles (Yazulla et al, 1989; Yazulla and Studholme 1997). Similarly to the β2/β3 subunits, the α1 subunit showed considerable intracellular labeling of cone terminals, with far less membrane‐bound labeling.…”

Section: Discussionmentioning

confidence: 99%

Postsynaptic localization of γ‐aminobutyric acid transporters and receptors in the outer plexiform layer of the goldfish retina: An ultrastructural study

Klooster¹,

Cardozo²,

Yazulla³

et al. 2004

J of Comparative Neurology

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The gamma-aminobutyric acid (GABA)-ergic system in the outer plexiform layer (OPL) of the goldfish retina was studied via light and electron immunohistochemistry. The subcellular distributions of immunoreactivity (-IR) of plasma membrane GABA transporters GAT2 and GAT3, the alpha1 and alpha3 subunits of the ionotropic GABA(A) receptor, and the rho1 subunit of the ionotropic GABA(C) receptor were determined. The localization of the GAT2-IR and GAT3-IR to horizontal cell dendrites at the base of the cone synaptic complex was the main characteristic at the ultrastructural level. Very rarely, GAT2-IR and GAT3-IR were found in horizontal cell dendrites innervating rod spherules. alpha1-IR and alpha3-IR were seen in wide bands in the OPL, whereas rho1-IR appeared as a narrow band in the OPL. Most alpha1-IR was intracellular in rod and cone terminals. Membrane-associated alpha1-IR was observed in cone pedicles but not in rod spherules; postsynaptic elements were also labeled. alpha3-IR was concentrated in the lateral elements of horizontal cell dendrites in cone pedicles. In contrast, rho1-IR was found mainly on the spinules of the horizontal cell dendrites in cone pedicles. In addition, in another type of cone pedicle, rho1-IR was found at the position of OFF-bipolar cell dendrites. alpha3-IR and rho1-IR were rarely found in horizontal cell dendrites innervating rods. We suggest that two GABAergic pathways exist in the outer retina- first, a GABAergic positive loop with GABA receptors mainly on the horizontal cell dendrites and spinules and, second, a GABAergic feedback pathway involving GABA receptors on cone pedicles and GABA transporters on horizontal cells and that this pathway presumably modulates feedback strength from horizontal cells to cones.

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“…This remodeling is then reversed in darkness. Synaptic vesicle density can also change with light- or dark-adaptation [59]. The mechanism(s) mediating the movement and remodeling of ribbon and active zone material is currently unknown, but P-Rex2-mediated activation of Rac1 leading to local remodeling of actin within the terminal is a plausible contributor.…”

Section: Discussionmentioning

confidence: 99%

P-Rex2, a Rac-guanine nucleotide exchange factor, is expressed selectively in ribbon synaptic terminals of the mouse retina

Sherry

Blackburn

2013

BMC Neurosci

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BackgroundPhosphatidylinositol (3,4,5)-trisphosphate-dependent Rac Exchanger 2 (P-Rex2) is a guanine nucleotide exchange factor (GEF) that specifically activates Rac GTPases, important regulators of actin cytoskeleton remodeling. P-Rex2 is known to modulate cerebellar Purkinje cell architecture and function, but P-Rex2 expression and function elsewhere in the central nervous system is unclear. To better understand potential roles for P-Rex2 in neuronal cytoskeletal remodeling and function, we performed widefield and confocal microscopy of specimens double immunolabeled for P-Rex2 and cell- and synapse-specific markers in the mouse retina.ResultsP-Rex2 was restricted to the plexiform layers of the retina and colocalized extensively with Vesicular Glutamate Transporter 1 (VGluT1), a specific marker for photoreceptor and bipolar cell terminals. Double labeling for P-Rex2 and peanut agglutinin, a cone terminal marker, confirmed that P-Rex2 was present in both rod and cone terminals. Double labeling with markers for specific bipolar cell types showed that P-Rex2 was present in the terminals of rod bipolar cells and multiple ON- and OFF-cone bipolar cell types. In contrast, P-Rex2 was not expressed in the processes or conventional synapses of amacrine or horizontal cells.ConclusionsP-Rex2 is associated specifically with the glutamatergic ribbon synaptic terminals of photoreceptors and bipolar cells that transmit visual signals vertically through the retina. The Rac-GEF function of P-Rex2 implies a specific role for P-Rex2 and Rac-GTPases in regulating the actin cytoskeleton in glutamatergic ribbon synaptic terminals of retinal photoreceptors and bipolar cells and appears to be ideally positioned to modulate the adaptive plasticity of these terminals.

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Light adaptation affects synaptic vesicle density but not the distribution of GABA _A receptors in goldfish photoreceptor terminals

Cited by 18 publications

References 61 publications

Endocannabinoids in the retina: From marijuana to neuroprotection

Endocannabinoids in the retina: From marijuana to neuroprotection

Postsynaptic localization of γ‐aminobutyric acid transporters and receptors in the outer plexiform layer of the goldfish retina: An ultrastructural study

P-Rex2, a Rac-guanine nucleotide exchange factor, is expressed selectively in ribbon synaptic terminals of the mouse retina

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Light adaptation affects synaptic vesicle density but not the distribution of GABA A receptors in goldfish photoreceptor terminals

Cited by 18 publications

References 61 publications

Endocannabinoids in the retina: From marijuana to neuroprotection

Endocannabinoids in the retina: From marijuana to neuroprotection

Postsynaptic localization of γ‐aminobutyric acid transporters and receptors in the outer plexiform layer of the goldfish retina: An ultrastructural study

P-Rex2, a Rac-guanine nucleotide exchange factor, is expressed selectively in ribbon synaptic terminals of the mouse retina

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Light adaptation affects synaptic vesicle density but not the distribution of GABA _A receptors in goldfish photoreceptor terminals