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S Yazulla

Publications and source records attributed to S Yazulla.

83 records · Page 5Linked to original sources
PubMedDate not supplied

Depletion of retinal dopamine increases brightness perception in goldfish.

The effect of unilateral depletion of retinal dopamine on goldfish visual behavior was studied using a behavioral reflex, the dorsal light reaction (DLR). Retinal dopamine was depleted by intraocular injections of 6-hydroxydopamine (6-OHDA) on two successive days. By 2 weeks postinjection, dopamine interplexiform cells (DA-IPC) were not detected using tyrosine-hydroxylase immunoreactivity (TH-IR). By 6 weeks postinjection, generation of DA-IPC was observed at the marginal zone and by 9 months postinjection, 2-3 rows of DA-IPC were present at the marginal zone. Neurites extended several hundred micrometers toward the central retina. By 2 weeks postinjection, all 6-OHDA lesioned fish tilted 7-15 deg toward the injected eye under uniform overhead illumination. The tilting did not occur under scotopic illumination and reappeared within 1 min of light adaptation. Quantitation of the DLR showed that 6-OHDA lesioned fish behaved as if light were 2.4 log units more intense to the injected eye. Partial recovery was observed by 9 months postinjection, paralleling the reappearance of DA-IPC at the marginal zone. Tilting also was induced by unilateral intraocular injection with D1 and D2 dopamine receptor antagonists, SCH 23390 and S(-)-sulpiride, respectively. Fish did not tilt if they were light adapted at the time of injection. Tilting was observed if the animals were dark-adapted for 3 h and left in the dark for 1 h postinjection. Fish tilted toward the drug-injected eye within 2 min of light adaptation and gradually returned to vertical within 2 h. The tilting response to S(-)-sulpiride was stronger (approximately 20 deg vs. approximately 5 deg) and occurred at lower concentration (1 microM vs. 10 microM) compared to SCH 23390. We conclude that dopamine depletion mimics the dorsal light reaction by increasing the luminosity output of the eye and that dopamine is directly involved in photopic luminosity function.

Animals↗
PubMedDate not supplied

Depletion of retinal dopamine does not affect the ERG b-wave increment threshold function in goldfish in vivo.

Increment threshold functions of the electroretinogram (ERG) b-wave were obtained from goldfish using an in vivo preparation to study intraretinal mechanisms underlying the increase in perceived brightness induced by depletion of retinal dopamine by 6-hydroxydopamine (6-OHDA). Goldfish received unilateral intraocular injections of 6-OHDA plus pargyline on successive days. Depletion of retinal dopamine was confirmed by the absence of tyrosine-hydroxylase immunoreactivity at 2 to 3 weeks postinjection as compared to sham-injected eyes from the same fish. There was no difference among normal, sham-injected or 6-OHDA-injected eyes with regard to ERG waveform, intensity-response functions or increment threshold functions. Dopamine-depleted eyes showed a Purkinje shift, that is, a transition from rod-to-cone dominated vision with increasing levels of adaptation. We conclude (1) dopamine-depleted eyes are capable of photopic vision; and (2) the ERG b-wave is not diagnostic for luminosity coding at photopic backgrounds. We also predict that (1) dopamine is not required for the transition from scotopic to photopic vision in goldfish; (2) the ERG b-wave in goldfish is influenced by chromatic interactions; (3) horizontal cell spinules, though correlated with photopic mechanisms in the fish retina, are not necessary for the transition from scotopic to photopic vision; and (4) the OFF pathway, not the ON pathway, is involved in the action of dopamine on luminosity coding in the retina.

Animals↗
PubMedDate not supplied

Glycine in the lizard retina: comparison to the GABA system.

Neurons likely to utilize glycine (GLY) as a neurotransmitter were identified immunocytochemically in the "all-cone" lizard retina and the basic anatomical organization of the retinal GLY and gamma-aminobutyric acid (GABA) systems was compared. Four types of GLY-immunoreactive (GLY-IR) neurons were identified. Most GLY-IR cells were amacrine cells, which comprised at least two types. GLY-IR interplexiform cells and ganglion cells also were identified. The first GLY-IR amacrine cell type was characterized by a small pyriform soma, located distal to the border of the inner plexiform layer (IPL), and fine dendrites. Most GLY-IR amacrine cells were of this type and several subtypes may exist within this group. The second amacrine cell type was characterized by a large, distally located soma and a large descending process. This amacrine cell type showed colocalization of GLY-IR and GABA-IR and comprised about 4% of the total GLY-IR amacrine cell population. Comparison of GLY-IR and GABA-IR on serial sections showed that GLY and GABA were present in largely separate neuronal populations. Generally, GLY-IR amacrine cells were smaller, more distally located in the inner nuclear layer and had finer dendrites than GABA-IR amacrine cells. Distribution of GLY-IR and GABA-IR in the outer plexiform layer and the inner plexiform layer differed considerably. Based on the segregated distribution of GLY-IR and GABA-IR in the synaptic layers of the lizard retina, GLY and GABA may have fundamentally different roles in retinal processing.

Animals↗
PubMedDate not supplied

Glutamate-, GABA-, and GAD-immunoreactivities co-localize in bipolar cells of tiger salamander retina.

The presence of inhibitory bipolar cells in salamander retina was investigated by a comparative analysis of the distribution of glutamate- and GABA-immunoreactivities (GLU-IR; GABA-IR) using a postembedding immunocytochemical method. GLU-IR was found in virtually all photoreceptors, bipolar cells and ganglion cells, neuronal elements that transfer information vertically through the retina. GLU-IR also was found in numerous amacrine cells in the mid and proximal inner nuclear layer as well as in the cytoplasm of horizontal cells, while the nucleus of horizontal cells was either lightly labeled or not labeled at all. GLU-IR was found in the outer plexiform layer and intensely in the inner plexiform layer, in which there was no apparent sublamination. Forty-seven percent of Type IB bipolar cells in the distal inner nuclear layer and 13% of the displaced bipolar cells were GABA-IR. All bipolar cells were also GLU-IR, indicating that GABA-IR bipolar cells were a subset of GLU-IR bipolar cells rather than a separate population. About 12% of the Type IB bipolar cells were moderately GABA-IR and likely comprised a GABAergic subtype. GLU-IR levels in the presumed GABAergic bipolar cells were higher than in other purely GLU-IR bipolar cells suggesting that these GABA-IR bipolar cells are glutamatergic as well. All of the displaced bipolar cells were only lightly GABA-IR, indicating that displaced bipolar cells comprise a more homogeneous class of glutamatergic cell than orthotopic bipolar cells. GAD-IR co-localized with GABA-IR in orthotopic but not displaced bipolar cells, further supporting the idea that some orthotopic bipolar cells are GABAergic. A small proportion of bipolar cells in salamander retina contain relatively high levels of both GABA and glutamate. Co-release of these substances by bipolar cells could contribute to the "push-pull" modulation of ganglion cell responses.

Animals↗
PubMedDate not supplied

Volume transmission of dopamine may modulate light-adaptive plasticity of horizontal cell dendrites in the recovery phase following dopamine depletion in goldfish retina.

We investigated the recovery of light-adaptive spinule formation following dopamine depletion with intraocular injection of 6-hydroxydopamine (6-OHDA) and subsequent neogeneration of dopamine interplexiform cells (DA-IPC) at the marginal zone. DA-IPCs were gone by 2 weeks postinjection and appeared at the marginal zone by 6 weeks postinjection, at which time DA-IPC neurites grew toward the central retina, reaching within 0.5 mm of the central retina by 1 year. Retinas from day time, light-adapted fish at 2 weeks, 4 weeks, 3 months, and 1 year postinjection with 6-OHDA were processed for pre-embedding tyrosine hydroxylase immunoreactivity (TOH-IR) and compared to sham-injected and control retinas at the electron-microscopical (EM) level. Only 6-OHDA fish that tilted markedly toward the injected eye were used for these experiments. The tilt mimics the dorsal light reaction, indicating a 2-2.5 log unit increase in the photopic sensitivity of the 6-OHDA eye. Spinule formation was reduced by about 60% in the 2- and 4-week 6-OHDA retinas, but returned to control levels throughout the entire retina of 3-month and 1 year 6-OHDA retinas even though the central region of these retinas contained no detectable TOH-IR. Intraocular injection with 10 microM SCH 23390 (a D1 antagonist) reduced light-adaptive spinule formation by 50% both in control eyes as well as those eyes that were 3 months post 6-OHDA injected. The full return of spinule formation with only partial reinnervation of the retina with DA-IPC processes and their subsequent inhibition by SCH 23390 indicates that dopamine diffused large distances within the retina to regulate this synaptic plasticity (i.e. displayed volume transmission). Also, since all 6-OHDA injected fish displayed an increased photopic sensitivity in the injected eye when sacrificed, we suggest that horizontal cell spinules are not required for photopic luminosity coding in the outer retina.

Adaptation, Ocular↗
PubMedDate not supplied

3H-adenosine uptake selectively labels rod horizontal cells in goldfish retina.

There are four types of horizontal cell in the goldfish retina, three cone- and one rod-type. The neurotransmitter of only one type, the H1 (cone) horizontal cell, has been identified as GABA. 3H-adenosine uptake was examined as a possible marker for the other classes of horizontal cell. Isolated goldfish retinae were incubated in 3H-adenosine (10-40 microCi) in HEPES-buffered saline for 30 min, then fixed, embedded in plastic, and processed for light-microscopic autoradiography (ARG). For double-label immuno/ARG studies, 1-micron-thick sections were processed for GABA postembed immunocytochemistry, then for ARG. 3H-adenosine uptake was localized to cone photoreceptors, presumed precursor cells in the proximal outer nuclear layer, and to a single, continuous row of horizontal cell bodies in the inner nuclear layer. No uptake was localized to the region of horizontal cell axon terminals. 3H-adenosine uptake did not colocalize with GABA-IR in H1 horizontal cells, but it did colocalize with adenosine deaminase immunoreactivity. It is concluded that 3H-adenosine uptake selectively labels rod horizontal cells in the goldfish retina based on position and staining pattern, which are similar to rod horizontal cells stained by Golgi or HRP injection methods. The use of 3H-adenosine uptake may provide a useful tool to study other properties of rod horizontal cells (i.e. development) as well as provide clues as to the transmitter used by these interneurons.

Adenosine↗
PubMedDate not supplied

Cannabinoid receptors on goldfish retinal bipolar cells: electron-microscope immunocytochemistry and whole-cell recordings.

Cannabinoid CB1 receptors are distributed throughout the CNS and interact with GABA, glutamate, and dopamine systems. Cannabinoids have effects on the visual system, some of which may have a retinal component, particularly the enhancement of photosensitivity. We used immunocytochemistry and whole-cell recording to study cannabinoids in the goldfish retina. Immunoblots of an antiserum against amino acids (1-14) of the rat CB1 receptor produced a single band in goldfish retina at about 70 kDa. Light microscope immunocytochemistry of CB1 receptor immunoreactivity (CB1R-IR) revealed intense staining of Müller cells and weaker staining of ON bipolar cells (verified with double labeling with PKC-IR) and the outer and inner plexiform layers. Ultrastructural analysis revealed that CB1R-IR was localized intracellularly as well as on the plasma membrane of photoreceptor terminals, bipolar cell terminals and, rarely, amacrine cell boutons. Membrane-associated CB1R-IR was restricted to cone pedicles at sites removed from the synaptic ribbon. Regarding bipolar cells, membrane-associated CB1R-IR was found at 93% of the synaptic terminals in sublamina b (ON-type) and only at 33% of the synaptic terminals in sublamina a (OFF-type). Whole-cell recordings from large ON-type Mb bipolar cells showed that the delayed rectifier (I(K(V))) was rapidly and reversibly inhibited by 1 microM of the cannabinoid agonists CP 54490 and (+)-WIN 55212-2, effects blocked completely by the antagonist SR 141716A (1 microM). Inhibition of I(K(V)) in the Mb bipolar cells by cannabinoids should result in a more tonic ON response to increments of light. As such, cannabinoids may play a role in modulating the temporal aspects of signaling in the retina.

Animals↗
PubMedDate not supplied

Dopamine depletion with 6-OHDA enhances dopamine D1-receptor modulation of potassium currents in retinal bipolar cells.

Ascorbate modulates IK(V) of ON-type mixed rod/cone bipolar cells (Mb) in the goldfish retinal slice through a dopamine D1/G-protein/PKA-coupled mechanism. We investigated the effects of dopamine depletion with intraocular injections of 6-OHDA on IK(V) and its modulation by ascorbate over 1-7 weeks following 6-OHDA treatment. Dopamine depletion was verified by tyrosine hydroxylase immunocytochemistry. Slices were perfused in a saline containing 200 microM sodium ascorbate. One-second puffs of ascorbate-free saline (zero [AA]o), delivered through a 2-3 microm diameter pipette, were directed at the bipolar cells. IK(V) was recorded by conventional whole-cell patch-clamp methods. In normal retinas, puffs of zero [AA]o caused a rapid (<100 ms) suppression of IK(V) of about 50% that lasted for several minutes. This effect was blocked by 1 microM SCH23390 and was unaffected by 2 mM Co2+ or 5 microM spiperone. 6-OHDA treatment resulted in major effects. First, IK(V) was reduced by approximately 50% for weeks 1-6, recovering to a 20% reduction by week 7. Second, puffs of zero [AA]o enhanced IK(V) rather than suppressed it. The enhancement was blocked by SCH23390 and the PKA inhibitor, Wiptide, but was insensitive to spiperone. Third, all parts of the Mb bipolar cell (except for the axon) were sensitive to puffs of zero [AA]o in both normal and 6-OHDA-treated retinas. Fourth, bath application of 20 microM dopamine restored the amplitude of IK(V) but did not reverse the effects of puffed zero [AA]o. IK(V) was fit by two exponentials; all of the effects on IK(V) were on the amplitude of the components and not on the time constants. Chronic dopamine depletion caused reversible changes in the properties of K+ channels underlying IK(V), as well as a long-term change in the intracellular coupling mechanisms between D1-receptor activation and the modulation of IK(V).

Adrenergic Agents↗
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Suppression of voltage-dependent K+ currents in retinal bipolar cells by ascorbate.

Ascorbate, often used as an antioxidant in neural studies, may also serve as a neuromodulator in the vertebrate central nervous system (CNS), in that it modulates the synaptic actions of glutamate and dopamine. Retina of fish contain a high concentration of ascorbate. The release and/or uptake of neurotransmitters are related to membrane potential, which to a large extent is determined by the activity of K+ channels. As retinal bipolar cells are subject to synaptic input from glutamatergic and dopaminergic sources, the effects of ascorbate on voltage-dependent K+ currents (I(K)(v)) of the mixed rod-cone ON-center bipolar cells (Mb) in goldfish retinal slices were studied using whole-cell recording techniques. I(K)(V) was suppressed reversibly 60% by 100-200 microM ascorbate. The effect of ascorbate was not due to changes in pH, oxidative stress, lipid peroxidation, any Ca2+-dependent or Na+-dependent action. However, the suppressive effect of ascorbate was blocked by cholera toxin and Wiptide, a protein kinase A (PKA) inhibitor. It is concluded that ascorbate, at physiological concentrations, inhibits I(K)(V) of bipolar cells via a Gs-protein-PKA system. This effect of ascorbate should be taken into account when using ascorbate as an antioxidant in retinal studies involving dopamine.

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PubMedDate not supplied

Modulation of voltage-dependent K+ currents (IK(V)) in retinal bipolar cells by ascorbate is mediated by dopamine D1 receptors.

Ascorbic acid (AA), a neuromodulator in the vertebrate CNS, is released from glutamatergic neurons in exchange with glutamate uptake and, in turn, modulates the release of both glutamate and dopamine. We have reported that voltage-gated K+ currents (IK(V)) in ON-mixed rod/cone bipolar cells (Mb) were suppressed 60% by 100-200 microM AA when added to an ascorbate-free solution. However, as the in vivo [AA]o in retina is about 200 microM, we studied the effects of changes in [AA]o on IK(V) when [AA]o was varied around a baseline concentration of 200 microM. Whole-cell currents were recorded with patch-clamp methods from goldfish Mb cells in retinal slices, bathed in a solution containing 200 microM AA. We found that (1) IK(V) was enhanced (180+/-36%, n = 9) by increases of [AA]o less than 40 microM with an average latency of 8 min. (2) However, IK(V) was suppressed without an appreciable latent period by two conditions: increases more than 40 microM [AA]o and decreases by any amount greater than 10 microM. (3) Effects of delta[AA]o on IK(V) were blocked by a D1 dopamine receptor antagonist, SCH 23390, but not by a D2 receptor antagonist, spiperone. Increased concentrations of a D1 agonist (SKF 38390) and dopamine had similar concentration-dependent effects on IK(V) as did AA, even in the presence of 200 microM ascorbate. Ascorbate has complicated concentration-dependent effects on IK(V) of Mb cells in vitro that were mediated by D1 dopamine receptors, suggesting that dopamine and ascorbate may be involved reciprocally in modulating IK(V), with consequences on the transmission of rod signals to the inner retina.

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