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Results for “Retinal Horizontal Cells”

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At least 55 records · Page 3Linked to original sources

PubMed2002

Down-regulation of glutamate-induced conductances of retinal horizontal cells after ganglion cell axotomy.

After a complete optic nerve section (ONS), retinal neurons may display retrograde transneuronal modifications in synaptic structure and function related to the retinal disconnection from the brain. The molecular and physiological basis of these changes is not yet fully understood. Immunoreactivity for calbindin was used to specifically immunolabel the horizontal cells (HC) in order to study any morphologic changes in the outer plexiform layer (OPL) after axotomy-induced degeneration of retinal ganglion cells (RGC) in the rabbit retina. Glutamate-gated conductance expressed by HC enzymatically dissociated from the rabbit retina were studied at 12 and 21 days after ONS by using the whole-cell voltage-clamp technique. The amplitudes of glutamate-induced currents on HC were significantly reduced 3 weeks after axotomy. However, no morphologic changes within the OPL were detected coincident with the progressive loss of glutamatergic responses; similarly, HC dissociated from the axotomized retinal tissue did not differ in morphology or appearance from control retinas. The main finding in this study is that the HC experiment a retrograde transneuronal down-regulation of their ionotropic glutamate-induced conductance following axotomy-induced degeneration of RGC.

Animals↗

PubMed2002

On the interaction between voltage-gated conductances and Ca(2+) regulation mechanisms in retinal horizontal cells.

The horizontal cell is a second-order retinal neuron that is depolarized in the dark and responds to light with graded potential changes. In such a nonspiking neuron, not only the voltage-gated ionic conductances but also Ca(2+) regulation mechanisms, e.g., the Na(+)/Ca(2+) exchange and the Ca(2+) pump, are considered to play important roles in generating the voltage responses. To elucidate how these physiological mechanisms interact and contribute to generating the responses of the horizontal cell, physiological experiments and computer simulations were made. Fura-2 fluorescence measurements made on dissociated carp horizontal cells showed that intracellular Ca(2+) concentration ([Ca(2+)]i) was maintained <100 nM in the resting state and increased with an initial transient to settle at a steady level of approximately 600 nM during prolonged applications of L-glutamate (L-glu, 100 microM). A preapplication of caffeine (10 mM) partially suppressed the initial transient of [Ca(2+)]i induced by L-glu but did not affect the L-glu-induced steady [Ca(2+)]i. This suggests that a part of the initial transient can be explained by the Ca(2+)-induced Ca(2+) release from the caffeine-sensitive Ca(2+) store. The Ca(2+) regulation mechanisms and the ionic conductances found in the horizontal cell were described by model equations and incorporated into a hemi-spherical cable model to simulate the isolated horizontal cell. The physiological ranges of parameters of the model equations describing the voltage-gated conductances, the glutamate-gated conductance and the Na(+)/Ca(2+) exchange were estimated by referring to previous experiments. The parameters of the model equation describing the Ca(2+) pump were estimated to reproduce the steady levels of [Ca(2+)]i measured by Fura-2 fluorescence measurements. Using the cable model with these parameters, we have repeated simulations so that the voltage response and [Ca(2+)]i change induced by L-glu applications were reproduced. The simulation study supports the following conclusions. 1) The Ca(2+)-dependent inactivation of the voltage-gated Ca(2+) conductance has a time constant of approximately 2.86 s. 2) The falling phase of the [Ca(2+)]i transient induced by L-glu is partially due to the inactivation of the voltage-gated Ca(2+) conductance. 3) Intracellular Ca(2+) is extruded mainly by the Na(+)/Ca(2+) exchange when [Ca(2+)]i is more than approximately 2 microM and by the Ca(2+) pump when [Ca(2+)]i is less than approximately 1 microM. 4) In the resting state, the Na(+)/Ca(2+) exchange may operate in the reverse mode to induce Ca(2+) influx and the Ca(2+) pump extrudes intracellular Ca(2+) to counteract the influx. The model equations of physiological mechanisms developed in the present study can be used to elucidate the underlying mechanisms of the light-induced response of the horizontal cell in situ.

Animals↗

PubMed2001

Analysis of spontaneous EPSCs in retinal horizontal cells of the carp.

Spontaneous excitatory postsynaptic currents (sEPSCs) were recorded under Whole-cell voltage clamp from carp type 1 horizontal cells (H1 cells) uncoupled by dopamine in retinal slices. Red light steps, which hyperpolarise cones and reduce glutamate release, induced outward current responses accompanied by a suppression of sEPSCs. sEPSCs decayed exponentially with a mean time constant of 0.71+/-0.07 ms and had a reversal potential near 0 mV. Power spectral analysis of sEPSCs revealed a similar decay time constant. They were suppressed by a non-NMDA receptor antagonist, CNQX at 10 microM, and a relatively specific AMPA receptor antagonist, GYKI52466 at 20 microM. The presence of sEPSCs suggests that the release of glutamate from cone synaptic terminals is vesicular. The reduction in mean sEPSC frequency with red light was not accompanied by a significant change in the mean sEPSC conductance increase (482+/-59 pS), suggesting that a decrease in the vesicular release rate from cones does not alter the vesicular glutamate concentration (quantal contents). The results suggest that the spontaneous events in H1 cells were contributed by non-NMDA (possibly AMPA) type glutamate receptors modulated by the red cone input.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2000

Modulation of coupling between retinal horizontal cells by retinoic acid and endogenous dopamine.

The regulation of electrical coupling between retinal neurons appears to be an important component of the neuronal mechanism of light adaptation, which enables the retina to operate efficiently over a broad range of light intensities. The information about the ambient light conditions has to be transmitted to the neuronal network of the retina and previous evidence has indicated that dopamine is an important neurochemical signal. In addition, recent studies suggest that another important chemical signal is retinoic acid, which is a light-correlated byproduct of the phototransduction cycle. This review summarizes the latest findings about the effects of dopamine and retinoic acid on gap junctional coupling in the retinas of mouse, rabbit and fish.

Animals↗

PubMed1993

Oncogene expression in retinal horizontal cells of transgenic mice results in a cascade of neurodegeneration.

The phenylethanolamine N-methyltransferase promoter directs the expression of the SV40 T antigen to subsets of amacrine and horizontal neurons of the retina in a line of transgenic mice. T antigen expression begins in these cells during the first postnatal week. The horizontal cells appear to develop normally for another week but then begin to die. Subsequently, most of the horizontal cells disappear from the central and mid retina, resulting in loss of the outer plexiform layer and absence of ribbon synapses between the photoreceptors and bipolar cells. Neuronal transformation occurs only in the peripheral retina. These experiments indicate that horizontal neurons are heterogeneous with respect to susceptibility to transformation and that T antigen expression in a subset of horizontal neurons can be a direct cause of neuronal cell death. Furthermore, critical interdependencies exist between horizontal neurons after retinal neurogenesis is complete.

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PubMed2002

Dopamine mediates circadian clock regulation of rod and cone input to fish retinal horizontal cells.

A circadian (24-hour) clock regulates the light responses of fish cone horizontal cells, second order neurones in the retina that receive synaptic contact from cones and not from rods. Due to the action of the clock, cone horizontal cells are driven by cones in the day, but primarily driven by rods at night. We show here that dopamine, a retinal neurotransmitter, acts as a clock signal for the day by increasing cone input and decreasing rod input to cone horizontal cells. The amount of endogenous dopamine released from in vitro retinae was greater during the subjective day than the subjective night. Application of dopamine or quinpirole, a dopamine D(2)-like agonist, during the subjective night increased cone input and eliminated rod input to the cells, a state usually observed during the subjective day. In contrast, application of spiperone, a D(2)-like antagonist, or forskolin, an activator of adenylyl cyclase, during the subjective day reduced cone input and increased rod input. SCH23390, a D(1) antagonist, had no effect. Application of R(p)-cAMPS, an inhibitor of cAMP-dependent protein kinase, or octanol, an alcohol that uncouples gap junctions, during the night increased cone input and decreased rod input. Because D(2)-like receptors are on photoreceptor cells, but not horizontal cells, the results suggest that the clock-induced increase in dopamine release during the day activates D(2)-like receptors on photoreceptor cells. The resultant decrease in intracellular cyclic AMP and protein kinase A activation then mediates the increase in cone input and decrease in rod input.

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PubMed1999

Glutathione depletion causes an uncoupling effect on retinal horizontal cells through oxidative stress.

To investigate a physiological role of glutathione in the horizontal cells of carp retina, the gap junctional intercellular communication between horizontal cells was studied using the techniques of intracellular recording of light-induced responses and coupling of the fluorescence dye Lucifer Yellow. Intravitreal injection of 2.5 micromol L-buthionine sulfoximine, an inhibitor of glutathione synthesis, induced a dramatic reduction (20% of control) of retinal glutathione level two days after treatment. The low level of glutathione continued for a further four to five days, and thereafter gradually recovered to about 40% (20 days after injection) and 70% (50 days after injection) of the control level. The spatial properties of the photopic L-type horizontal cell response were examined by enlarging the diameter of the central spot and peripheral annulus over the recording point. In normal retinas, the response amplitude of horizontal cells was monotonically enhanced as the diameter of the spot increased (0.5-4.0 mm) and correspondingly the dye diffusion area was wide, as the injected Lucifer Yellow normally diffused to several neighboring cells. Treatment with L-buthionine sulfoximine significantly altered the spatial properties of horizontal cells by increasing the response amplitude to central spots and slightly decreasing that to peripheral annuli, which were observed by four days after injection. It also restricted intracellular Lucifer Yellow to one or two cells. Accompanying the recovery of the cellular level of glutathione, the spatial properties and dye coupling of horizontal cells were restored to normal. A time lag (two days) of initiation in retinal glutathione depletion and alteration of spatial or dye coupling properties of horizontal cells is discussed, together with reactive oxygen species accumulation.

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PubMed1990

Properties of non-NMDA excitatory amino acid-activated channels in isolated retinal horizontal cells.

The excitatory amino acid glutamate is believed to be the neurotransmitter used by some photoreceptors in the teleost retina. Past studies have shown that exogenous glutamate, and its analogs, are capable of affecting second-order retinal neurons in a manner consistent with the action of a photoreceptor transmitter. In an effort to characterize the properties of retinal glutamate channels on second-order neurons, non-NMDA excitatory amino acid-activated channels were studied in single horizontal cells isolated from the retina of the white bass. Using patch-clamp techniques single glutamate, kainate, and quisqualate channels were recorded. Two categories of channels were observed. The first was labeled slow-channels. Single-channel conductances and open times for this channel showed a range of values, but the average for channels activated by glutamate was 12 pS and 5.6 msec; quisqualate, 8.5 pS and 8.8 msec; and kainate, 8.5 pS and 4.5 msec. Openings of slow-channels elicited by the agonists tended to occur in bursts with a mean burst length of 38 msec. The bursts were punctuated by numerous, brief closings. The second channel category was termed fast channels. The agents glutamate, quisqualate, and kainate all activated channels in this category with open times of 1-2 msec and 2 prominent conductances in the range of about 10 and 20-30 pS. Activity of the fast channels tended to be noisy and no bursting behavior was observed.

Animals↗

PubMed2000

Light-adaptive effects of retinoic acid on receptive field properties of retinal horizontal cells.

Besides its role in ocular development, retinoic acid (RA), which is a light-correlated byproduct of the phototransduction cycle, was recently shown to affect light-driven synaptic plasticity in the outer plexiform layer of the adult fish retina. Tuning by ambient light conditions of the retinal network properties is very prominent in outer plexiform layer circuits, and we therefore examined whether RA could affect cone horizontal cell physiology similar to ambient light. Performing intracellular recordings and dye injections in the dark-adapted inverted eyecup preparation of the carp, we found that RA reduced the receptive fields of horizontal cell somata and impaired gap junctional communication. This action was not observed among coupled axon terminals of horizontal cells and appeared to be stereospecific because it could only be attributed to all-trans and 13-cis RA but not to the 9-cis isomer and photoisomerized all-trans RA. Modulation of receptive field size occurred independently of the dopaminergic system. Furthermore, RA affected the light responsiveness of cone horizontal cells. Compared to the dark-adapted condition, responsiveness to intense light stimulation was enhanced but decreased when low intensities were used. Moreover, following RA treatment H2-type horizontal cells of dark-adapted retinae which do not give rise to colour-opponent light properties became colour-opponent and performed depolarizing responses to long-wavelength stimulation. In all these cases RA perfectly matched the effects of light adaptation, supporting the notion that RA acts as an endogenous neuromodulator.

Acyclic Monoterpenes↗

PubMed1991

Rods and cones activate different excitatory amino acid receptors on the mudpuppy retinal horizontal cell.

We have studied rod and cone neurotransmission onto horizontal cells (HCs) of the mudpuppy retina by: (1) dual whole-cell recordings from synaptically connected pairs in a superfused retinal slice preparation, and (2) intracellular recordings from HCs in a superfused retina-eyecup preparation. In the presence of relatively weak concentrations of broad spectrum excitatory amino acid antagonists, HC recordings show that cone-mediated responses were significantly more attenuated than those mediated by rods. These observations suggest that the HC postsynaptic receptors for rods and cones are pharmacologically different. One advantage of having distinct rod- and cone-activated receptors on second-order neurons may be to preserve different rod and cone functions under varying levels of light stimulation and provide separate means of regulating rod and cone neurotransmission onto the second-order cells.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1988

Measurement of DC and AC spectral sensitivities of retinal horizontal cells by "voltage clamp by light".

The method of "voltage clamp by light" was applied to measure spectral sensitivities of second-order visual neurons, namely L- and R/G-type horizontal cells in the carp retina. The present equipment employs (i) a ceramic photomodulator to facilitate a fast servomechanical control of retinal illuminance, (ii) an electronic circuit to compensate for the synaptic transmission delay, and (iii) a manual selection switch for the system to operate on negative feedback for either depolarizing or hyperpolarizing responses to light. These features allowed us to determine quickly and simultaneously both DC and AC spectral sensitivities, although the AC case was examined only at 1 Hz in this report. In L-type cells, the AC spectral sensitivity was similar in shape to the DC result. These sensitivity curves differed from microphotospectrometric absorption of red-sensitive cones: in L-type cells at both ends of the visible spectrum and in R/G units with deep-red light.

Animals↗

PubMed1992

APB suppresses synaptic input to retinal horizontal cells in fish: a direct action on horizontal cells modulated by intracellular pH.

1. Membrane potentials and cone-driven light responses were recorded from the H1-type horizontal cells in isolated retinas. Membrane potentials and intracellular pH were recorded also in enzymatically dissociated solitary horizontal cells. 2. In isolated retinas the glutamate analogue 2-amino-4-phosphonobutyrate (APB) hyperpolarized horizontal cells and reduced their light responses in a dose-dependent manner (5-200 microM). 3. The action of APB depended on the formulation of the saline; APB was effective in L-15 saline buffered with N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) but not in a commonly used, nominally CO2-free bicarbonate/Tris-buffered saline. 4. The major factor controlling the potency of APB was intracellular pH. APB was ineffective during retinal perfusion with NH4Cl-containing or CO2-free bicarbonate saline, both of which are known to alkalinize cells. In contrast, APB was effective in salines formulated to acidify the retinal neurons. These included both HEPES and Tris-buffered salines containing a weak acid and bicarbonate/Tris-buffered saline gassed with CO2. 5. APB reduced the size of glutamate-evoked depolarizations in solitary horizontal cells but had no independent action in the absence of glutamate. This reduction of glutamate-induced depolarization was observed in salines formulated to block voltage-dependent calcium and potassium currents. 6. The magnitude of APB's antagonistic action on solitary horizontal cells increased in a dose-dependent manner from 10 to 200 microM. The antagonism was increased by intracellular acidification and was reduced or eliminated by alkalinization. 7. We conclude that APB can reduce glutamate-evoked and, by inference, the photoreceptor neurotransmitter-evoked depolarization of horizontal cells by acting directly on the horizontal cells. This effect of APB is modulated by intracellular pH.

Aminobutyrates↗

PubMed2004

Neurotransmitter modulation of extracellular H+ fluxes from isolated retinal horizontal cells of the skate.

Self-referencing H(+)-selective microelectrodes were used to measure extracellular H(+) fluxes from horizontal cells isolated from the skate retina. A standing H(+) flux was detected from quiescent cells, indicating a higher concentration of free hydrogen ions near the extracellular surface of the cell as compared to the surrounding solution. The standing H(+) flux was reduced by removal of extracellular sodium or application of 5-(N-ethyl-N-isopropyl) amiloride (EIPA), suggesting activity of a Na(+)-H(+) exchanger. Glutamate decreased H(+) flux, lowering the concentration of free hydrogen ions around the cell. AMPA/kainate receptor agonists mimicked the response, and the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) eliminated the effects of glutamate and kainate. Metabotropic glutamate agonists were without effect. Glutamate-induced alterations in H(+) flux required extracellular calcium, and were abolished when cells were bathed in an alkaline Ringer solution. Increasing intracellular calcium by photolysis of the caged calcium compound NP-EGTA also altered extracellular H(+) flux. Immunocytochemical localization of the plasmalemma Ca(2+)-H(+)-ATPase (PMCA pump) revealed intense labelling within the outer plexiform layer and on isolated horizontal cells. Our results suggest that glutamate modulation of H(+) flux arises from calcium entry into cells with subsequent activation of the plasmalemma Ca(2+)-H(+)-ATPase. These neurotransmitter-induced changes in extracellular pH have the potential to play a modulatory role in synaptic processing in the outer retina. However, our findings argue against the hypothesis that hydrogen ions released by horizontal cells normally act as the inhibitory feedback neurotransmitter onto photoreceptor synaptic terminals to create the surround portion of the centre-surround receptive fields of retinal neurones.

Animals↗

PubMed2000

Vertebrate ancient-long opsin: a green-sensitive photoreceptive molecule present in zebrafish deep brain and retinal horizontal cells.

Nonretinal/nonpineal photosensitivity has been found in the brain of vertebrates, but the molecular basis for such a "deep brain" photoreception system remains unclear. We conducted an extensive search for brain opsin cDNAs of the zebrafish (Danio rerio), a useful animal model for genetic studies, and we have isolated a partial cDNA clone encoding an ortholog of vertebrate ancient (VA) opsin, the function of which is unknown. Subsequent characterization revealed the occurrence of two kinds of mRNAs encoding putative splicing variants, VA and VA-Long (VAL) opsin, the latter of which is a novel variant of the former. Both opsins shared a common core sequence in the membrane-spanning domains, but VAL-opsin had a C-terminal tail much longer than that of VA-opsin. Functional reconstitution experiments on the recombinant proteins showed that VAL-opsin with bound 11-cis-retinal is a green-sensitive pigment (lambdamax approximately 500 nm), whereas VA-opsin exhibited no photosensitivity even in the presence of 11-cis-retinal. Immunoreactivity specific to this functionally active VAL-opsin was localized at a limited number of cells surrounding the diencephalic ventricle of central thalamus, and these cells were distributed over approximately 200 micrometer along the rostrocaudal axis. Taken together with the previous study on the locus of the teleost brain photosensitivity (von Frisch K, 1911), it is strongly suggested that the VAL-positive cells in the zebrafish brain represent the deep brain photoreceptors. The VAL-specific immunoreactivity was also detected in a subset of non-GABAergic horizontal cells in the zebrafish retina. The existence of VAL-opsin, a new member of the rhodopsin superfamily, in these tissues may indicate its multiple roles in visual and nonvisual photosensory physiology.

Animals↗

PubMed1993

Novel GABA responses from rod-driven retinal horizontal cells.

gamma-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central nervous system. Two classes of GABA receptors (GABAA and GABAB) have been identified. GABAA receptors are ligand-gated chloride channels that are competitively antagonized by bicuculline, noncompetitively blocked by picrotoxin, and often allosterically modulated by barbiturates and benzodiazepines. GABAB receptors regulate potassium and calcium channels through G-protein and intracellular second-messenger pathways, are selectively activated by baclofen, and are antagonized by phaclofen and 2-hydroxysaclofen. For some years, evidence has accumulated that there are GABA receptors, especially prominent along visual pathways, which are neither antagonized by bicuculline nor activated by baclofen, but are activated by certain conformationally restricted analogues of GABA, including cis-4-aminocrotonic acid (CACA). These receptors have been designated GABAC receptors. As yet, membrane current responses from isolated neurons that reflect this novel pharmacology have not been reported, although such responses have been recorded from oocytes injected with retinal messenger RNA. Here we describe a chloride-mediated current response from isolated rod-driven horizontal cells (H4) of the white perch retina that has this novel pharmacology.

Animals↗

PubMedDate not supplied

The circadian component of spinule dynamics in teleost retinal horizontal cells is dependent on the dopaminergic system.

During the light phase of a light/dark cycle, dendrites of teleost cone horizontal cells display numerous finger-like projections, called spinules, which are formed at dawn and degraded at dusk, and are thought to be involved in chromatic feedback processes. We have studied the oscillations of these spinules during a normal light/dark cycle and during 48 h of constant darkness in two groups of strongly rhythmic, diurnal fish, Aequidens pulcher. In one group the retinal dopaminergic system had been destroyed by the application of 6-OHDA, while in the other (control) group, the dopaminergic system was intact. In control fish, oscillations of spinule numbers were observed under both normal and constant dark conditions, indicating the presence of a robust circadian rhythm. However, spinule dynamics were severely affected by the absence of retinal dopamine. During the normal light phase, the number of spinules in 6-OHDA injected retinae was strongly reduced, and throughout continual darkness, spinule formation was almost completely suppressed. These results indicate that dopamine is essential for both light-evoked and circadian spinule formation; furthermore, we conclude that there is no circadian oscillator within horizontal cells controlling the formation of spinules.

Animals↗

PubMed1989

Functional role of spines in the retinal horizontal cell network.

Compartmental models derived from serial electron-microscopic reconstructions of horizontal cell processes entering cone pedicles and rod spherules are used to show that these processes have the morphological and electrical characteristics of dendritic spines. Properties of these spines are incorporated into a distributed model of the horizontal cell network. Expressions relating the magnitude of conductance changes applied at the spine heads to hyperpolarization of cells within the network are derived. Model analyses show that spine properties play a critical role in determining network responses. Specifically, increasing spine stem resistance increases the network input resistance and space constant, hyperpolarizes the resting potential, decreases response to full-field light stimuli, and increases response to small light spots. Increasing spine-stem resistance also decouples potential at the spine head from potential at the cell body. This result suggests that the location of feedback neurotransmitter release sites (e.g., at the spine heads versus the cell body) may have a profound influence on properties of horizontal cell inhibition of cone response. Because of these important functional consequences, structurally realistic models of the horizontal cell network must incorporate spine properties.

Animals↗

PubMed1990

Wavelength-dependent temporal properties of retinal horizontal cells in turtles.

Electrical responses of luminosity horizontal cells (L cells) to monochromatic stimuli were analyzed by intracellular recordings in the retinas of the freshwater turtle (Pseudemys scripta elegans) and of the sea turtle (Chelonia mydas mydas). Light intensity, duration, and wavelength were varied to assess temporal effects. For a given intensity of monochromatic light, response amplitude increased with stimulus duration until maximum amplitude occurred at a specific duration. This suprathreshold metric of temporal integration is called here summation time, and it is wavelength-dependent. L cells always had some level of red-sensitive cone input, although in some cells inputs from green- and blue-sensitive cones were also observed. For these latter cells, summation times were shorter for 640-nm than for 540-nm or 450-nm lights. These results were most evident in cells that received dominant inputs from blue- or green-sensitive cones. Responses of some other L cells were almost completely dominated by inputs from red-sensitive cones. Summation times of these cells were not wavelength-dependent. But when these inputs also included green-sensitive cones, shorter summation times were obtained to 640-nm light than to 540-nm light, even though dominant inputs were still from red-sensitive cones. These results, obtained from both retinal and 3,4-dehydroretinal photopigment systems, are consistent with reported observations in Pseudemys scripta elegans that show linear responses of red-sensitive cones to have shorter integration times and times-to-peak than green-sensitive cones. Responses from horizontal cells dominated by blue-sensitive cone inputs were the most sensitive of all; they also had the longest summation times.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗