ON cone bipolar cells in rat express the metabotropic receptor mGluR6

1997 ◽  
Vol 14 (4) ◽  
pp. 789-794 ◽  
Author(s):  
Noga Vardi ◽  
Katsuko Morigiwa

AbstractThe rod bipolar cell and about five types of ON cone bipolar cells depolarize to light by employing a sign-reversing metabotropic glutamate receptor. Glutamate responses are similar in both rod bipolar and cone bipolar cells, but the receptor mediating this response (mGluRo) was so far demonstrated only in rod bipolar cells. To test if ON cone bipolar cells also express mGluR6, we immunoreacted rat retina with an antibody specific for mGluRo, and studied the staining from serial ultrathin sections. We demonstrate that mGluR6 is indeed expressed in the dendritic tips of cone bipolar cells, the majority of which receive a ribbon synapse, and thus probably are ON cone bipolar cells. We further show that half of the dendritic tips contacting the cones stain for mGluR6, thus implying that all ON cone bipolar cell types express mGluR6.

1998 ◽  
Vol 79 (3) ◽  
pp. 1384-1395 ◽  
Author(s):  
Thomas Euler ◽  
Heinz Wässle

Euler, Thomas and Heinz Wässle. Different contributions ofGABAA and GABAC receptors to rod and cone bipolar cells in a rat retinal slice preparation. J. Neurophysiol. 79: 1384–1395, 1998. Whole cell currents were recorded from rod and cone bipolar cells in a slice preparation of the rat retina. Use of the gramicidin D perforated-patch technique prevented loss of intracellular compounds. The recorded cells were identified morphologically by injection with Lucifer yellow. During the recordings, the cells were isolated synaptically by extracellular cobalt. To distinguish the γ-aminobutyric acid (GABA) receptors pharmacologically, theGABAA receptor antagonist, bicuculline, and the GABAC receptor antagonist, 3-aminopropyl(methyl)phosphinic acid, were used. In all bipolar cells tested, application of GABA induced postsynaptic chloride currents that hyperpolarized the cells from their resting potential of about −40 mV. GABA was applied at different concentrations to allow for the different affinity of GABA at GABAA and GABAC receptors. At a GABA concentration of 25 μM, in the case of rod bipolar cells, ∼70% of the current was found to be mediated by GABAC receptors. In the case of cone bipolar cells, only ∼20% of the current was mediated by GABAC receptors. Furthermore, this GABAC-mediated fraction varied among the different morphological types of cone bipolar cells, supporting the hypothesis of distinct functional roles for the different types of cone bipolar cells. There is evidence that the efficacy of GABAC receptors is modulated by glutamate through metabotropic glutamate receptors. We tested this hypothesis by applying agonists of metabotropic glutamate receptors (mGluR)1/5 to rod bipolar cells. The specific agonist (±)-trans-azetidine-2,4-dicarboxylic acid and the potent mGluR agonist quisqualic acid reduced the amplitude of the GABAC responses by 10–30%. This suggests a functional role for the modulation of GABAC receptors by the metabotropic glutamate receptors mGluR1/5.


2007 ◽  
Vol 98 (6) ◽  
pp. 3423-3435 ◽  
Author(s):  
Alyosha Molnar ◽  
Frank Werblin

Retinal bipolar cells can be divided into on and off types based on the polarity of their response to light. Bipolar activity is further shaped by inhibitory inputs, characterized here by the events that occur immediately after the onset of a light step: 1) in most off bipolar cells, excitatory current decreased, whereas inhibitory current increased. These currents reinforced each other, enhancing the light response. 2) In about half of the on cone bipolar cells, the excitatory current increased, whereas inhibitory current decreased, also reinforcing the light response. Both of these reinforcing interactions were mediated by glycinergic inhibition. 3) In the remaining on cone bipolar cells, excitation and inhibition both increased, but inhibition was delayed so that these cells responded transiently. 4) Finally, in rod bipolar cells, excitation and inhibition both increased so that inhibition suppressed excitation, reducing the light response at all time scales. The suppressive inhibition seen in on cone and rod bipolar cells was mediated by GABA. Thus morphologically diverse bipolar cells receive only four main types of inhibitory input, and the majority of “inhibitory” inputs actually serve to enhance excitation.


2020 ◽  
Author(s):  
Amanda J. McLaughlin ◽  
Kumiko A. Percival ◽  
Jacqueline Gayet-Primo ◽  
Teresa Puthussery

AbstractAdapting between scotopic and photopic illumination involves switching the routing of retinal signals between rod and cone-dominated circuits. In the daytime, cone signals pass through parallel On and Off cone bipolar cells, that are sensitive to increments and decrements in luminance, respectively. At night, rod signals are routed into these cone-pathways via a key glycinergic interneuron, the AII amacrine cell (AII-AC). In primates, it is not known whether AII-ACs contact all Off-bipolar cell types indiscriminately, or whether their outputs are biased towards specific Off-bipolar cell types. Here, we show that the rod-driven glycinergic output of AII-ACs is strongly biased towards a subset of macaque Off-cone bipolar cells. The Off-bipolar types that receive this glycinergic input have sustained physiological properties and include the Off-midget bipolar cells, which provide excitatory input to the Off-midget ganglion cells (parvocellular pathway). The kinetics of the glycinergic events are consistent with the involvement of the α1 glycine receptor subunit. Taken together with results in mouse retina, our findings point towards a conserved motif whereby rod signals are preferentially routed into sustained Off signaling pathways.Significance StatementVisual signals pass through different retinal neurons depending on the prevailing level of illumination. Under night-time light levels, signals from rods pass through the AII amacrine cell, an inhibitory interneuron that routes rod signals into On and Off bipolar cells to detect increments and decrements in light intensity, respectively. Here, we show in primate retina that the output of AII amacrine cells is strongly biased towards specific Off bipolar cell types, which suggests that rod signals reach the brain via specific neural channels. Our results further our understanding of how visual signals are routed through visual circuits during night-time vision.


2001 ◽  
Vol 18 (5) ◽  
pp. 675-685 ◽  
Author(s):  
GREGORY S. McGILLEM ◽  
RAMON F. DACHEUX

The superfused retinal slice preparation was used to examine the morphology and glutamate-activated whole-cell currents of rabbit bipolar cells. There were six morphologically distinct types of cone bipolar cells and a rod bipolar cell that had axon terminals stratifying in stratum 3 to 5 of sublamina-b. All of these bipolar cell types exhibited an outward current in response to the application of the metabotropic glutamate receptor, mGluR6, agonist AP-4 (APB), and had I/V curves indicative of membrane channel closure. Conversely, there were no currents activated during the application of kainate, the AMPA/kainate receptor agonist. These data demonstrate they were on-bipolar cells. In addition, there were six morphologically distinct cone bipolar cells that stratified in sublamina-a. Every cell with axonal arborizations in stratum 1 and 2 exhibited an inward current when the ionotropic glutamate receptor agonist kainate was applied. This current was blocked by application of the AMPA/kainate receptor antagonist CNQX. These cells also decreased their membrane resistance in response to kainate, a characteristic of the opening of channels within the plasma membrane. Without exception, no cells stratifying in sublamina-a responded to the mGluR6 agonist AP-4, further identifying them as off-bipolar cells.


1993 ◽  
Vol 10 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Ann H. Milam ◽  
Dennis M. Dacey ◽  
Alexander M. Dizhoor

AbstractHuman, macaque monkey, and rat retinas were immunostained with a polyclonal antibody preparation against purified recoverin, a 23-kD calcium-binding protein isolated from bovine retina that localizes to rods and cones (Dizhoor et al., 1991). In addition to immunoreactive photoreceptors, we have identified subpopulations of recoverin-positive bipolar cells in all three species. Results from immunostaining with progressive dilutions of anti-recoverin and preadsorption of the antibody with a dilution series of purified recoverin showed that photoreceptors and bipolar cells had similar affinities for the antibody and suggested that the molecule recognized by the antibody in both cell types is recoverin. Immunoreactivity for recoverin and protein kinase C, a selective marker for all rod bipolar cells, was found in separate bipolar cell populations. Recoverin immunoreactivity is therefore a characteristic of certain cone bipolar cell types.In rat retina, anti-recoverin labeled two morphologically distinct subpopulations of cone bipolar cells whose axonal arbors stratified at different depths in the inner plexiform layer (IPL). The bipolar cells labeled with anti-recoverin did not correspond to those that were reactive for calbindin, another cone bipolar cell marker.Human and monkey retinas also had two populations of cone bipolar cells that were recoverin-positive. One population showed a distinct pattern of narrow bistratification at the outer border of the IPL and a regular mosaic arrangement of its axonal arbors, suggesting that the entire population of a single cone bipolar type was labeled. Cell density, dendritic morphology, and axonal-field size and stratification indicate that anti-recoverin selectively stains the flat midget (presumed OFF-center) cone bipolar cell type observed previously in Golgi preparations. By contrast the second bipolar cell population had axonal stratification in the inner half of the IPL and showed an unusual but consistent morphology and spatial distribution. Individual cells were intensely stained but were present at an extremely low density (~2−5 cells/mm2). These cells had multibranched dendritic trees characteristic of the diffuse bipolar cell class, but very small axonal fields in the size range of the midget bipolar class. Neither of the two recoverin-positive bipolar cell types in monkey was labeled with anti-calbindin or anti-cholecystokinin. An antibody preparation against bovine pineal hydroxyindole-O-methyltransferase (HIOMT) labeled photoreceptors and bipolar cells that closely resembled the recoverin-positive bipolar cells in human and rat retinas. Preadsorption of this antibody preparation with purified recoverin abolished immunostaining of the bipolar cells, suggesting that the anti-HIOMT preparation contains antibodies against recoverin, which is known to be present in the bovine pineal gland.


2005 ◽  
Vol 93 (1) ◽  
pp. 84-93 ◽  
Author(s):  
Kwoon Y. Wong ◽  
Alan R. Adolph ◽  
John E. Dowling

Electroretinograms (ERGs) were recorded from the giant danio ( Danio aequipinnatus) to study glutamatergic input mechanisms onto bipolar cells. Glutamate analogs were applied to determine which receptor types mediate synaptic transmission from rods and cones to on and off bipolar cells. Picrotoxin, strychnine, and tetrodotoxin were used to isolate the effects of the glutamate analogs to the photoreceptor–bipolar cell synapse. Under photopic conditions, the group III metabotropic glutamate receptor (mGluR) antagonist (RS)-α-cyclopropyl-4-phosphonophenylglycine (CPPG) only slightly reduced the b-wave, whereas the excitatory amino acid transporter (EAAT) blocker dl- threo-β-benzyl-oxyaspartate (TBOA) removed most of it. Complete elimination of the b-wave required both antagonists. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX) blocked the d-wave. Under scotopic conditions, rod and cone inputs onto on bipolar cells were studied by comparing the sensitivities of the b-wave to photopically matched green and red stimuli. The b-wave was >1 log unit more sensitive to the green than to the red stimulus under control conditions. In CPPG or l-AP4 (l-(+)-2-amino-4-phosphonobutyric acid, a group III mGluR agonist), the sensitivity of the b-wave to the green stimulus was dramatically reduced and the b-waves elicited by the 2 stimuli became nearly matched. The d-wave elicited by dim green stimuli, which presumably could be detected only by the rods, was eliminated by NBQX. In conclusion: 1) cone signals onto on bipolar cells involve mainly EAATs but also mGluRs (presumably mGluR6) to a lesser extent; 2) rods signal onto on bipolars by mainly mGluR6; 3) off bipolar cells receive signals from both photoreceptor types by AMPA/kainate receptors.


1997 ◽  
Vol 14 (1) ◽  
pp. 103-109 ◽  
Author(s):  
Thomas E. Hughes

AbstractThere is some evidence that the mammalian rod bipolar cell expresses ionotropic glutamate receptors. This is surprising in light of the strong evidence that the glutamate released by the rod photoreceptor acts upon a metabotropic glutamate receptor-mGluRo-present in the dendrites of the rod bipolar cell. To reexamine the issue of which glutamate receptor subunits may be present on the rod bipolar cell, an immunohistochemical study of acutely dissociated retinal cells was undertaken. Two monoclonal antibodies provided some evidence that GluR2 and/or GluR4, as well as NMDAR1 subunit, are present on the rod bipolar cell. A monoclonal antibody directed against the N-terminus of GluR2 labeled the rod bipolar cells, but two antisera directed against the C-terminus of the same subunit did not. One possible explanation for this discrepancy could be that the rare splice variant GluR2-long, which is endowed with a different C-terminus, could be expressed by the rod bipolar cell. To explore this possibility, RT-PCR was used to amplify the transcripts encoding GluR2 in the neural retina. This revealed that GluR2-long transcripts, with the flop exon, are present.


2017 ◽  
Vol 34 ◽  
Author(s):  
PATRICK W. KEELEY ◽  
JASON J. KIM ◽  
SAMMY C.S. LEE ◽  
SILKE HAVERKAMP ◽  
BENJAMIN E. REESE

AbstractRetinal bipolar cells spread their dendritic arbors to tile the retinal surface, extending them to the tips of the dendritic fields of their homotypic neighbors, minimizing dendritic overlap. Such uniform nonredundant dendritic coverage of these populations would suggest a degree of spatial order in the properties of their somal distributions, yet few studies have examined the patterning in retinal bipolar cell mosaics. The present study examined the organization of two types of cone bipolar cells in the mouse retina, the Type 2 cells and the Type 4 cells, and compared their spatial statistical properties with those of the horizontal cells and the cholinergic amacrine cells, as well as to random simulations of cells matched in density and constrained by soma size. The Delauney tessellation of each field was computed, from which nearest neighbor distances and Voronoi domain areas were extracted, permitting a calculation of their respective regularity indexes (RIs). The spatial autocorrelation of the field was also computed, from which the effective radius and packing factor (PF) were determined. Both cone bipolar cell types were found to be less regular and less efficiently packed than either the horizontal cells or cholinergic amacrine cells. Furthermore, while the latter two cell types had RIs and PFs in excess of those for their matched random simulations, the two types of cone bipolar cells had spatial statistical properties comparable to random distributions. An analysis of single labeled cone bipolar cells revealed dendritic arbors frequently skewed to one side of the soma, as would be expected from a randomly distributed population of cells with dendrites that tile. Taken together, these results suggest that, unlike the horizontal cells or cholinergic amacrine cells which minimize proximity to one another, cone bipolar cell types are constrained only by their physical size.


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