The effects of serotonin agonists and antagonists on the response properties of complex ganglion cells in the rabbit's retina

1988 ◽  
Vol 1 (2) ◽  
pp. 181-188 ◽  
Author(s):  
William J. Brunken ◽  
Nigel W. Daw
Keyword(s):  
Synaptic Transmission ◽  
Spontaneous Activity ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Orientation Selectivity ◽  
Bipolar Cells ◽  
Evoked Responses ◽  
Selective Agonists ◽  
Rod Bipolar Cells

AbstractSelective agonists and antagonists were employed to determine the role of indoleaminergic amacrine cells in the generation of the light-evoked responses and spontaneous activity of direction and orientation selective cells. Perfusion with 5-HT2 antagonists reduced the spontaneous activity and both the leading and trailing edge responses of ON/OFF direction selective cells. 5-HT1a agonists had a similar effect on this class of cell, namely, a reduction of light-evoked and spontaneous activity. Results from ON-center and OFF-center orientation selective cells were consistent with those obtained from direction selective cells in that no disruption of direction or orientation selectivity was observed during perfusion of these drugs. These data suggest that the indoleaminergic cells are not directly involved in the generation of the trigger features of complex ganglion cells, but may be facilitating synaptic transmission in the inner retina. This function is discussed relative to the connectivity of the rod bipolar cells and the putative indoleaminergic amacrine cells. The similarity of the effects of 5-HT1a agonists and 5-HT2 antagonists supports the hypothesis, developed during our prior studies of brisk ganglion cells, that these two receptor classes mediate antagonistic processes in the target neurons.

A role for 5HT3 receptors in visual processing in the mammalian retina

1993 ◽  
Vol 10 (3) ◽  
pp. 511-522 ◽  
Author(s):  
William J. Brunken ◽  
Xiao-Tao Jin
Keyword(s):  
Visual Processing ◽  
Ganglion Cells ◽  
Cell Activity ◽  
Phosphatidyl Inositol ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Reciprocal Effect ◽  
Mammalian Retina ◽  
Messenger System

AbstractWe investigated the role of 5HT3 receptors in the mammalian retina using electrophysiological techniques to monitor ganglion cell activity. Activation of 5HT3 receptors with the selective agonist 1-phenylbiguanide (PBG) increased the ON responses of ON-center ganglion cells, while decreasing the OFF responses of OFF-center cells. The application of a selective 5HT3 antagonist had a reciprocal effect, namely it reduced the center response in ON-center cells and concomitantly increased the center responses in OFF-center cells. Since putative serotoninergic amacrine cells in the retina are connected specifically to the rod bipolar cell, these agents most likely affect the rod bipolar terminal. These data, together with previous studies, suggest that both 5HT2 and 5HT3 receptors mediate an excitatory influence which serves to facilitate the output from rod bipolar cells, the former via a phosphatidyl inositol second-messenger system, and the latter via a direction channel.

Unique functional properties of the APB sensitive and insensitive rod pathways signaling light decrements in mouse retinal ganglion cells

2006 ◽  
Vol 23 (1) ◽  
pp. 127-135 ◽  
Author(s):  
GUO-YONG WANG
Keyword(s):  
Functional Properties ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Mouse Retina ◽  
Clear Cut ◽  
Types Of Information ◽  
Rod Bipolar Cells ◽  
Rod Pathway ◽  
Cone Bipolar Cells

Light decrements are mediated by two distinct groups of rod pathways in the dark-adapted retina that can be differentiated on the basis of their sensitivity to the glutamate agonist DL-2-amino-phosphonobutyric (APB). By means of the APB sensitive pathway, rods transmit light decrementsviarod bipolar cells to AII amacrine cells, then to Off cone bipolar cells, which in turn innervate the dendrites of Off ganglion cells. APB hyperpolarizes rod bipolar cells, thus blocking this rod pathway. With APB insensitive pathways, rods either directly synapse onto Off cone bipolar cells, or rods pass light decrement signal to cones by gap junctions. In the present study, whole-cell patch-clamp recordings were made from ganglion cells in the dark-adapted mouse retina to investigate the functional properties of APB sensitive and insensitive rod pathways. The results revealed several clear-cut differences between the APB sensitive and APB insensitive rod pathways. The latency of Off responses to a flashing spot of light was significantly shorter for the APB insensitive pathways than those for the APB sensitive pathway. Moreover, Off responses of the APB insensitive pathways were found to be capable of following substantially higher stimulus frequencies. Nitric oxide was found to selectively block Off responses in the APB sensitive rod pathway. Collectively, these results provide evidence that the APB sensitive and insensitive rod pathways can convey different types of information signaling light decrements in the dark-adapted retina.

Distribution of protein kinase C isoforms in the cat retina

2002 ◽  
Vol 19 (5) ◽  
pp. 549-562 ◽  
Author(s):  
BOZENA FYK-KOLODZIEJ ◽  
WENHUI CAI ◽  
ROBERTA G. POURCHO
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Inner Plexiform Layer ◽  
Kinase C ◽  
Cat Retina ◽  
Rod Bipolar Cells ◽  
Cone Bipolar Cells

Immunocytochemical localization was carried out for five isoforms of protein kinase C (PKC) in the cat retina. In common with other mammalian species, PKCα was found in rod bipolar cells. Staining was also seen in a small population of cone bipolar cells with axon terminals ramifying near the middle of the inner plexiform layer (IPL). PKCβI was localized to rod bipolar cells, one class of cone bipolar cell, and numerous amacrine and displaced amacrine cells. Staining for PKCβII was seen in three types of cone bipolar cells as well as in amacrine and ganglion cells. Immunoreactivity for both PKCε and PKCζ was found in rod bipolar cells; PKCε was also seen in a population of cone bipolar cells and a few amacrine and ganglion cells whereas PKCζ was found in all ganglion cells. Double-label immunofluorescence studies showed that dendrites of the two PKCβII-positive OFF-cone bipolar cells exhibit immmunoreactivity for the kainate-selective glutamate receptor GluR5. The third PKCβII cone bipolar is an ON-type cell and did not stain for GluR5. The retinal distribution of these isoforms of PKC is consistent with a role in modulation of various aspects of neurotransmission including synaptic vesicle release and regulation of receptor molecules.

Light-Evoked Responses of Bipolar Cells in a Mammalian Retina

2000 ◽  
Vol 83 (4) ◽  
pp. 1817-1829 ◽  
Author(s):  
Thomas Euler ◽  
Richard H. Masland
Keyword(s):  
Gaba Receptor ◽  
Dynamic Range ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Chloride Current ◽  
Evoked Responses ◽  
Temporal Properties ◽  
Cation Current ◽  
Rod Bipolar Cells ◽  
Cone Bipolar Cells

We recorded light-evoked responses from rod and cone bipolar cells using patch-clamp techniques in a slice preparation of the rat retina. Rod bipolar cells responded to light with a sustained depolarization (on response) followed at light offset by a slight hyperpolarization. on and off cone bipolar cells were encountered, both with diverse temporal properties. The responses of rod bipolar cells were composed primarily of two components, a nonspecific cation current and a chloride current. The chloride current was reduced greatly in axotomized cells and could be suppressed by coapplication of the GABAA antagonist bicuculline and the GABAC antagonist (1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid. This suggests that it largely reflects feedback from GABAergic amacrine cells. The response latency of intact rod bipolar cells was shorter than that of the axotomized cells, and the sensitivity curve covered more than twice the dynamic range. Application of the GABA receptor antagonists partially mimicked the effects of axotomy. These findings suggest that functional properties of the axon terminal system—notably synaptic feedback from amacrine cells—play an important role in defining the response properties of mammalian bipolar cells.

GABAAreceptors in the retina of the cat: An immunohistochemical study of wholemounts, sections, and dissociated cells

1991 ◽  
Vol 6 (3) ◽  
pp. 229-238 ◽  
Author(s):  
Thomas E. Hughes ◽  
Ulrike Grönert ◽  
Harvey J. Karten
Keyword(s):  
Immunohistochemical Study ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Small Cells ◽  
Peripheral Retina ◽  
Inner Plexiform Layer ◽  
Gamma Aminobutyric Acid ◽  
Initial Portion ◽  
Rod Bipolar Cells

AbstractGamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter used by many neurons of the mammalian retina. To identify the synaptic targets of these cells, we undertook an immunohistochemical study with a monoclonal antibody that recognizes the GABAAreceptors (62−3G1, generously donated by A. de Blas). This antibody labels the somata of at least one group of amacrine cells in the inner nuclear layer. It also labels two groups of somata in the ganglion cell layer: one small and the other much larger. The small cells are likely to be displaced amacrine cells based on their size, although some could be gamma ganglion cells. The much larger receptor-positive cells are clearly ganglion cells, based both on their size and the antibody labeling of the initial portion of their axon. In the peripheral retina, the size of these large somata suggests that many are beta ganglion cells. However, at any point across the retina the density of these cells never exceeded 50% of the density of beta cells as a whole.The antibody also labels a dense plexus of processes that extends throughout the inner plexiform layer (IPL), with a marked concentration in the inner third of the layer. This is the portion of the IPL in which the rod bipolar cells terminate. It is difficult to recognize processes of individual cells in the IPL, so retinae were dissociated. The rod bipolar cells were identified by protein kinase C immunoreactivity (Negishi et al., 1988; Karschin & Wässle, 1990). They were not labeled by the GABAAreceptor antibody. This is surprising in light of tight-seal, whole cell voltage-clamp recordings that have shown that the rod bipolars express functional GABAAreceptors. One possible explanation is that the antibody recognizes only a subset of the GABAAreceptors.

scholarly journals Functional NMDA receptors are expressed by both AII and A17 amacrine cells in the rod pathway of the mammalian retina

2016 ◽  
Vol 115 (1) ◽  
pp. 389-403 ◽  
Author(s):  
Yifan Zhou ◽  
Barbora Tencerová ◽  
Espen Hartveit ◽  
Margaret L. Veruki
Keyword(s):  
Nmda Receptors ◽  
Low Frequency ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Evoked Responses ◽  
Patch Clamp Recording ◽  
Mammalian Retina ◽  
Frequency Stimulation ◽  
Rod Bipolar Cells ◽  
Rod Pathway

At many glutamatergic synapses, non- N-methyl-d-aspartate (NMDA) and NMDA receptors are coexpressed postsynaptically. In the mammalian retina, glutamatergic rod bipolar cells are presynaptic to two rod amacrine cells (AII and A17) that constitute dyad postsynaptic partners opposite each presynaptic active zone. Whereas there is strong evidence for expression of non-NMDA receptors by both AII and A17 amacrines, the expression of NMDA receptors by the pre- and postsynaptic neurons in this microcircuit has not been resolved. In this study, using patch-clamp recording from visually identified cells in rat retinal slices, we investigated the expression and functional properties of NMDA receptors in these cells with a combination of pharmacological and biophysical methods. Pressure application of NMDA did not evoke a response in rod bipolar cells, but for both AII and A17 amacrines, NMDA evoked responses that were blocked by a competitive antagonist (CPP) applied extracellularly and an open channel blocker (MK-801) applied intracellularly. NMDA-evoked responses also displayed strong Mg2+-dependent voltage block and were independent of gap junction coupling. With low-frequency application (60-s intervals), NMDA-evoked responses remained stable for up to 50 min, but with higher-frequency stimulation (10- to 20-s intervals), NMDA responses were strongly and reversibly suppressed. We observed strong potentiation when NMDA was applied in nominally Ca2+-free extracellular solution, potentially reflecting Ca2+-dependent NMDA receptor inactivation. These results indicate that expression of functional (i.e., conductance-increasing) NMDA receptors is common to both AII and A17 amacrine cells and suggest that these receptors could play an important role for synaptic signaling, integration, or plasticity in the rod pathway.

scholarly journals Activation of rod input in a model of retinal degeneration reverses retinal remodeling and induces formation of normal synapses, circuitry and visual signaling in the adult retina

2018 ◽  
Author(s):  
Tian Wang ◽  
Johan Pahlberg ◽  
Jon Cafaro ◽  
Alapakkam P. Sampath ◽  
Greg D. Field ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Retinal Ganglion Cells ◽  
Bipolar Cell ◽  
Ganglion Cells ◽  
Bipolar Cells ◽  
Mouse Retina ◽  
Retinal Ganglion ◽  
Rod Photoreceptors ◽  
Retinal Remodeling ◽  
Rod Bipolar Cells

AbstractA major cause of human blindness is the death of rod photoreceptors. As rods degenerate, synaptic structures between rod and rod bipolar cells dissolve and the rod bipolar cells extend their dendrites and occasionally make aberrant contacts. Such changes are broadly observed in blinding disorders caused by photoreceptor cell death and is thought to occur in response to deafferentation. How the remodeled retinal circuit affect visual processing following rod rescue is not known. To address this question, we generated transgenic mice wherein a disrupted cGMP-gated channel (CNG) gene can be repaired at the endogenous locus and at different stages of degeneration by tamoxifen-inducible cre-mediated recombination. In normal rods, light-induced closure of CNG channels leads to hyperpolarization of the cell, reducing neurotransmitter release at the synapse. Similarly, rods lacking CNG channel exhibit a resting membrane potential that was ~10mV hyperpolarized compared to WT rods, indicating diminished glutamate release. Retinas from these mice undergo stereotypic retinal remodeling as a consequence of rod malfunction and degeneration. Upon tamoxifen-induced expression of CNG channels, rods recovered their structure and exhibited normal light responses. Moreover, we show that the adult mouse retina displays a surprising degree of plasticity upon activation of rod input. Wayward bipolar cell dendrites establish contact with rods to support normal synaptic transmission, which is propagated to the retinal ganglion cells. These findings demonstrate remarkable plasticity extending beyond the developmental period and support efforts to repair or replace defective rods in patients blinded by rod degeneration.Significance StatementCurrent strategies for treatment of neurodegenerative disorders are focused on the repair of the primary affected cell type. However, the defective neuron functions within a complex neural circuitry, which also becomes degraded during disease. It is not known whether a rescued neuron and the remodeled circuit will establish communication to regain normal function. We show that the adult mammalian neural retina exhibits a surprising degree of plasticity following rescue of rod photoreceptors. The wayward rod bipolar cell dendrites re-establish contact with rods to support normal synaptic transmission, which is propagated to the retinal ganglion cells. These findings support efforts to repair or replace defective rods in patients blinded by rod cell loss.

Membrane currents evoked by ionotropic glutamate receptor agonists in rod bipolar cells in the rat retinal slice preparation

1996 ◽  
Vol 76 (1) ◽  
pp. 401-422 ◽  
Author(s):  
E. Hartveit
Keyword(s):  
Nmda Receptor ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Inner Plexiform Layer ◽  
Receptor Agonists ◽  
Long Latency ◽  
Glutamate Receptor Agonists ◽  
Conductance Increase ◽  
Rod Bipolar Cells

1. With the use of the whole cell voltage-clamp technique, I have recorded the current responses to ionotropic glutamate receptor agonists of rod bipolar cells in vertical slices of rat retina. Rod bipolar cells constitute a single population of cells and were visualized by infrared differential interference contrast video microscopy. They were targeted by the position of their cell bodies in the inner nuclear layer and, after recording, were visualized in their entirety by labeling with the fluorescent dye Lucifer yellow, which was included in the recording pipette. To study current-voltage relationships of evoked currents, voltage-gated potassium currents were blocked by including Cs+ and tetraethylammonium+ in the recording pipette. 2. Pressure application of the non-N-methyl-D-aspartate (non-NMDA) receptor agonists kainate and (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) from puffer pipettes evoked a long-latency conductance increase selective for chloride ions. When the intracellular chloride concentration was increased, the reversal potential changed, corresponding to the change in equilibrium potential for chloride. The response was evoked in the presence of 5 mM Co2+ and nominally O mM Ca2+ in the extracellular solution, presumably blocking all external Ca2(+)-dependent release of neurotransmitter. 3. The long latency of kainate-evoked currents in bipolar cells contrasted with the short-latency currents evoked by gamma-aminobutyric acid (GABA) and glycine in rod bipolar cells and by kainate in amacrine cells. 4. Application of NMDA evoked no response in rod bipolar cells. 5. Coapplication of AMPA with cyclothiazide, a blocker of agonist-evoked desensitization of AMPA receptors, enhanced the conductance increase compared with application of AMPA alone. Coapplication of the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione blocked the response to kainate and AMPA, indicating that the response was mediated by conventional ionotropic glutamate receptors. 6. The conductance increase evoked by non-NMDA receptor agonists could not be blocked by a combination of 100 microM picrotoxin and 10 microM strychnine. Application of the GABAC receptor antagonist 3-aminopropyl (methyl)phosphinic acid (3-APMPA) strongly reduced the response, and coapplication of 500 microM 3-APMPA and 100 microM picrotoxin completely blocked the response. These results suggested that the conductance increase evoked by non-NMDA receptor agonists was mediated by release of GABA and activation of GABAC receptors, and most likely also GABAA receptors, on rod bipolar cells. 7. Kainate responses like those described above could not be evoked in bipolar cells in which the axon had been cut somewhere along its passage to the inner plexiform layer during the slicing procedure. This suggests that the response was dependent on the integrity of the axon terminal in the inner plexiform layer, known to receive GABAergic synaptic input from amacrine cells. 8. The results indicate that ionotropic glutamate receptors are not involved in mediating synaptic input from photoreceptors to rod bipolar cells and that an unconventional mechanism of GABA release from amacrine cells might operate in the inner plexiform layer.

scholarly journals Dopamine D1 receptor activation contributes to light-adapted changes in retinal inhibition to rod bipolar cells

2018 ◽  
Vol 120 (2) ◽  
pp. 867-879 ◽  
Author(s):  
Michael D. Flood ◽  
Johnnie M. Moore-Dotson ◽  
Erika D. Eggers
Keyword(s):  
Light Adaptation ◽  
Amacrine Cell ◽  
Amacrine Cells ◽  
Receptor Activation ◽  
Bipolar Cells ◽  
D1 Receptor ◽  
D1 Receptors ◽  
Light Responses ◽  
Dopamine Modulation ◽  
Rod Bipolar Cells

Dopamine modulation of retinal signaling has been shown to be an important part of retinal adaptation to increased background light levels, but the role of dopamine modulation of retinal inhibition is not clear. We previously showed that light adaptation causes a large reduction in inhibition to rod bipolar cells, potentially to match the decrease in excitation after rod saturation. In this study, we determined how dopamine D1 receptors in the inner retina contribute to this modulation. We found that D1 receptor activation significantly decreased the magnitude of inhibitory light responses from rod bipolar cells, whereas D1 receptor blockade during light adaptation partially prevented this decline. To determine what mechanisms were involved in the modulation of inhibitory light responses, we measured the effect of D1 receptor activation on spontaneous currents and currents evoked from electrically stimulating amacrine cell inputs to rod bipolar cells. D1 receptor activation decreased the frequency of spontaneous inhibition with no change in event amplitudes, suggesting a presynaptic change in amacrine cell activity in agreement with previous reports that rod bipolar cells lack D1 receptors. Additionally, we found that D1 receptor activation reduced the amplitude of electrically evoked responses, showing that D1 receptors can modulate amacrine cells directly. Our results suggest that D1 receptor activation can replicate a large portion but not all of the effects of light adaptation, likely by modulating release from amacrine cells onto rod bipolar cells. NEW & NOTEWORTHY We demonstrated a new aspect of dopaminergic signaling that is involved in mediating light adaptation of retinal inhibition. This D1 receptor-dependent mechanism likely acts through receptors located directly on amacrine cells, in addition to its potential role in modulating the strength of serial inhibition between amacrine cells. Our results also suggest that another D2/D4 receptor-dependent or dopamine-independent mechanism must also be involved in light adaptation of inhibition to rod bipolar cells.

Voltage- and transmitter-gated currents in isolated rod bipolar cells of rat retina

1990 ◽  
Vol 63 (4) ◽  
pp. 860-876 ◽  
Author(s):  
A. Karschin ◽  
H. Wassle
Keyword(s):  
Ion Channels ◽  
Outward Current ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Similar Distribution ◽  
Isolated Cells ◽  
Membrane Hyperpolarization ◽  
Rat Retina ◽  
Inward Current ◽  
Rod Bipolar Cells

1. Bipolar cells were isolated from adult rat retinas after enzymatic and mechanical treatment. The cells could be unequivocally identified from their morphology because of high retention of their axon and dendritic processes after isolation. 2. Protein kinase C (PKC) immunoreactivity performed on sections of the rat retina labeled rod bipolar cells and a few amacrine cells. Virtually all bipolar cells in the dissociates expressed PKC immunoreactivity and were, therefore, rod bipolar cells. 3. Rod bipolar cells were examined with the tight-seal whole-cell and excised-patch recording techniques. Resting potentials of the isolated cells recorded under current-clamp conditions showed a broad unimodal distribution around -37 mV. 4. Membrane depolarization from a holding potential of -90 mV resulted in an outward current. A fast sodium inward current was not observed. Membrane hyperpolarization from a holding potential of -40 mV activated an inwardly rectifying current. 5. gamma-Aminobutyric acid (GABA) and glycine, the putative retinal neurotransmitters that mediate the bipolar cells' receptive field surround in vivo, activated chloride conductances in almost all isolated bipolar cells. GABA- and glycine-evoked currents were both desensitizing and could be antagonized by the classical blockers bicuculline, picrotoxin, and strychnine, respectively. 6. Pressure application of the drugs from fine microcapillaries to various parts of the isolated cells suggests a high GABA sensitivity at the axonal endings compared with either the somatic or dendritic region. A similar distribution was not found for glycine. On the contrary, glycine-induced single-channel events with main conductances of 52 and 34 pS were recorded from membrane patches excised from the cells' somata. 7. Conductances induced by glutamate and several excitatory amino acid agonists were observed in a number of the cells. Application of the glutamate agonist 2-amino-4-phosphonobutyric acid (APB) induced an inward current at negative holding potentials associated with the opening of ion channels. In only 5 of 93 cells, APB closed ion channels, leading to a decrease in membrane conductance.

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