SEARCH · PubMed Health

Results for “Retinal Bipolar Cells”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources

PubMed2006

H244R VSX1 is associated with selective cone ON bipolar cell dysfunction and macular degeneration in a PPCD family.

PURPOSE: To elucidate the retinal dysfunction and the molecular basis of posterior polymorphous corneal dystrophy (PPCD) associated with macular dystrophy, both inherited in a dominant manner through a three-generation family. METHODS: Ophthalmologic examinations including slit lamp examination, visual acuity tests, fundus visualization by scanning laser ophthalmoscopy, fluorescein angiography, color vision tests, electro-oculography, photopic and scotopic electroretinography (ERG) according to the International Society for Clinical Electrophysiology of Vision (ISCEV) protocols, and oscillatory potential (OP) recordings were conducted on affected family members. Corneal button from one affected patient was examined by transmission electron microscopy. All exons and intron-exon boundaries of the VSX1 and the COL8A2 genes were amplified by polymerase chain reaction and sequenced. RESULTS: The presence of endothelial cells that have epithelial-like features with multiple layers, desmosomal junctions, and microvillous projections supports the diagnosis of PPCD. Sequence analysis indicated that the H244R variant in the VSX1 segregated with corneal and macular disease phenotypes in this family. Electrophysiologic studies indicated normal scotopic ERG findings, decreased amplitude of the photopic b-wave, photopic OP2 and OP3 barely recordable with a preserved OP4 amplitude, and variably decreased 30-Hz flicker amplitude. CONCLUSIONS: The human VSX1 is required for cone ON bipolar cell function but not for rod and cone OFF bipolar cells, giving a unique example of such a selective heritable retinal defect in humans. Furthermore, the authors provide the first clinical support for a new alternative role of VSX1 in cone biology, probably similar to that proposed for its goldfish ortholog during retinal differentiation.

Adult↗

PubMed2007

Rod bipolar cells and horizontal cells form displaced synaptic contacts with rods in the outer nuclear layer of the nob2 retina.

The nob2 mouse carries a null mutation in the Cacna1f gene, which encodes the pore-forming subunit of the L-type calcium channel, Ca(v)1.4. The loss of the electroretinogram b-wave in these mice suggests a severe reduction in transmission between photoreceptors and second-order neurons in the retina and supports a central role for the Ca(v)1.4 calcium channel at photoreceptor ribbon synapses, to which it has been localized. Here we show that the loss of Ca(v)1.4 leads to the aberrant outgrowth of rod bipolar cell dendrites and horizontal cell processes into the outer nuclear layer (ONL) of the nob2 retina and to the formation of ectopic synaptic contacts with rod photoreceptors in the ONL. Ectopic contacts are predominantly between rods and rod bipolar cells, with horizontal cell processes also present at some sites. Ectopic contacts contain apposed pre- and postsynaptic specializations, albeit with malformed synaptic ribbons. Cone photoreceptor terminals do not participate in ectopic contacts in the ONL. During retinal development, ectopic contacts appear in the days after eye opening, appearing progressively farther into the ONL at later postnatal stages. Ectopic contacts develop at the tips of rod bipolar cell dendrites and are less frequently associated with the tips of horizontal cell processes, consistent with the adult phenotype. The relative occurrence of pre- and postsynaptic markers in the ONL during development suggests a mechanism for the formation of ectopic synaptic contacts that is driven by the retraction of rod photoreceptor terminals and neurite outgrowth by rod bipolar cell dendrites.

Animals↗

PubMed1991

Purkinje cell protein-2 regulatory regions and transgene expression in cerebellar compartments.

The Purkinje cell protein 2 (Pcp-2) is expressed in cerebellar Purkinje cells and retinal bipolar neurons. To illuminate how Pcp-2 expression is restricted to only two neuronal types and to derive tools to express heterologous genes in these neuronal subpopulations, genomic sequences of the mouse Pcp-2 gene have been cloned and flanking sequences have been evaluated as a source of neuron-specific regulatory elements. An upstream region with homology to other genes expressed in neurons was identified and a hybrid gene containing this sequence was constructed by ligating 0.4 kb of upstream and 0.3 kb of downstream Pcp-2-flanking DNA to lacZ. Transgenic mice bearing this construct exhibited beta-galactosidase in a wide array of neuron types, suggesting that this sequence may play an important role in specifying neuronal expression. Addition of a further 3.1 kb of Pcp-2 upstream sequences restricted expression of beta-galactosidase to a small number of neuron types and most notably to Purkinje cells within parasagitally oriented cerebellar compartments. The presence of elements lying within the 3.1-kb upstream region and acting to specifically restrict Pcp-2 expression is therefore suggested. Moreover, as beta-galactosidase was not expressed in the bipolar cells of these transgenic mice, retinal expression of the endogenous Pcp-2 gene must involve elements in addition to those conferring expression within Purkinje cells.

Amino Acid Sequence↗

PubMed2005

Glycine modulates the center response of ON type rod-dominant bipolar cells in carp retina.

Effects of glycine on ON type rod-dominant bipolar cells (RBCs) were studied in isolated, superfused carp retina by intracellular recording technique and in carp retinal slice preparation by whole cell recording. Glycine of 4mM hyperpolarized RBCs and potentiated their light responses to large light spots, which was reversed by co-application of 10 microM strychnine. It was further found that illumination of the receptive field surround did not affect the depolarizing center response of RBCs. The above result therefore suggests that glycine modulates the center response of RBCs. Focal application of glycine to either dendrites or axon terminals of RBCs failed to induce any currents in both isolated cell and retinal slice preparations. On the other hand, glycine of 4mM increased the amplitude of the scotopic electroretinographic PIII component, which reflects the activity of rod photoreceptors. It seems likely that modulation by glycine of the RBC center response may be in part ascribed to a consequence of the potentiation of rod responses by glycine.

Animals↗

PubMed1996

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

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.

Animals↗

PubMed2006

Presynaptic mechanism for slow contrast adaptation in mammalian retinal ganglion cells.

Visual neurons, from retina to cortex, adapt slowly to stimulus contrast. Following a switch from high to low contrast, a neuron rapidly decreases its responsiveness and recovers over 5-20 s. Cortical adaptation arises from an intrinsic cellular mechanism: a sodium-dependent potassium conductance that causes prolonged hyperpolarization. Spiking can drive this mechanism, raising the possibility that the same mechanism exists in retinal ganglion cells. We found that adaptation in ganglion cells corresponds to a slowly recovering afterhyperpolarization (AHP), but, unlike in cortical cells, this AHP is not primarily driven by an intrinsic cellular property: spiking was not sufficient to generate adaptation. Adaptation was strongest following spatial stimuli tuned to presynaptic bipolar cells rather than the ganglion cell; it was driven by a reduced excitatory conductance, and it persisted while blocking GABA and glycine receptors, K((Ca)) channels, or mGluRs. Thus, slow adaptation arises from reduced glutamate release from presynaptic (nonspiking) bipolar cells.

Action Potentials↗

PubMed1992

Properties of depolarizing bipolar cell responses to central illumination in salamander retinal slices.

The voltage and current responses of depolarizing bipolar cells to central illumination were studied by means of whole-cell recording in retinal slices of the larval tiger salamander, Ambystoma tigrinum. To stabilize the responses, it was necessary to limit exchanges between the cytosol and the solution in the patch pipette by reducing the diameter of the pipette tip opening. The current-voltage relationship of the cell membrane in darkness displayed a strong outward rectification, and the inward current evoked by light could be consistently reversed by depolarization only when tetraethylammonium was added to the pipette solution. As a result of the membrane non-linearity, increases in the intensity of bright lights caused relatively smaller amplitude increases in the voltage than in the current responses and the latter had a proportionally smaller after-effect. With larger pipette tip openings, the cytosol equilibrated with the pipette filling solution. Under these conditions the light-evoked responses gradually became slower and acquired an on-off pattern, their final amplitude and polarity being determined by the ratio of the chloride concentrations on each side of the cell membrane. This finding is interpreted as revealing the existence of two response components: a chloride-dependent on-off increase in conductance and a faster depolarizing input that was lost through diffusional exchange. Addition of GTP and ATP to the electrode filling solution had a stabilizing effect on the labile component, whether or not cyclic GMP was also included. Observations on the magnitude of the conductance changes and on diphasic reversals indicate that the labile response component, presumably representing direct input from photoreceptors, is caused by an increase in conductance. The resulting inward current was still present at a low intracellular chloride concentration and may be assumed, therefore, to be carried by a cation influx.

Ambystoma↗

PubMed2006

Mouse opsin promoter-directed Cre recombinase expression in transgenic mice.

PURPOSE: Gene inactivation with homologous recombination in mice is a widely used tool to study gene function. However, many proteins play essential roles in a number of tissues and germline gene inactivation often results in embryonic lethality. To overcome this limitation and to dissect the functions of essential genes beyond embryonic development, we generated mouse rod opsin promoter-controlled cre transgenic mice with a goal of obtaining transgenic lines with a range of Cre activity in rod photoreceptors. METHODS: Transgenic mice expressing Cre recombinase directed by a long or short mouse opsin promoter were generated. Candidate Cre-expressing lines were identified with RT-PCR and Western blot analysis. Potentially useful Cre-expressing lines were characterized further with immunohistochemistry, PCR, and functional analysis using a Cre-activatable lacZ reporter mouse strain (R26R) to determine temporal and spatial patterns of Cre expression. Retinal function and morphology in these mouse lines were analyzed with electroretinography (ERG) and light microscopy of hematoxylin and eosin stained retinal sections. RESULTS: Transgenic mice expressing Cre in rod photoreceptors were generated. Characterization of candidate photoreceptor-specific Cre mice using immunohistochemistry and functional assays demonstrated that an efficient Cre-mediated recombination occurred in rod photoreceptor cells in one mouse line and a mosaic Cre-mediated recombination occurred in rod photoreceptors and rod bipolar cells in another mouse line. Further analysis of these mice with ERG and morphological examination suggested that the retinas of eight-month-old adults were normal. CONCLUSIONS: We have generated transgenic mice expressing Cre recombinase in rod photoreceptors. One transgenic mouse line was capable of carrying out efficient Cre-mediated recombination in rod photoreceptors. Another transgenic mouse line was capable of carrying out mosaic Cre-mediated recombination in rod photoreceptors and bipolar cells across the whole retina. These mice will be useful tools for Cre/lox-based gene activation and inactivation, as well as genetic mosaics, in rod photoreceptors and rod bipolar cells.

Animals↗

PubMed1998

Neurite outgrowth from bipolar and horizontal cells after experimental retinal detachment.

PURPOSE: To study the responses of horizontal cells and rod bipolar cells, the second-order neurons in the retina, to the degeneration induced by experimental retinal detachment. METHODS: Retinas from the eyes of domestic cats were examined 1, 3, 7, and 28 days after detachment using immunocytochemical and electron microscopic analyses. Retinal sections were labeled with antibodies to synaptophysin, calbindin D, and protein kinase C (PKC), proteins that serve as markers for synaptic terminals, horizontal cells, and rod bipolar cells, respectively. RESULTS: Beginning 1 day after detachment, the outer plexiform layer becomes disorganized and synaptophysin-labeled photoreceptor terminals are detected among the cell bodies of photoreceptors in the outer nuclear layer (ONL). At the same time, horizontal and rod bipolar cell processes grow into the ONL. In some cases, these processes contact photoreceptor terminals that have withdrawn deep into the ONL. Double-labeling experiments with antibodies to glial fibrillary acidic protein (Müller cell labeling) and phosphodiesterase gamma (cone labeling) demonstrate that the calbindin D- and PKC-positive neurite outgrowths are not derived from either Müller cells or cone photoreceptors. CONCLUSIONS: Horizontal and rod bipolar cell processes lengthen after retinal detachment, perhaps in response to a withdrawal of their presynaptic targets, the photoreceptor synaptic terminals. This apparent attempt to maintain synaptic contact after injury demonstrates a plasticity in the adult retina that may be of importance for the recovery of vision in human patients.

Animals↗

PubMed2006

Activation of a presynaptic glutamate transporter regulates synaptic transmission through electrical signaling.

Whereas glutamate transporters in glial cells and postsynaptic neurons contribute significantly to re-uptake of synaptically released transmitter, the functional role of presynaptic glutamate transporters is poorly understood. Here, we used electrophysiological recording to examine the functional properties of a presynaptic glutamate transporter in rat retinal rod bipolar cells and its role in regulating glutamatergic synaptic transmission between rod bipolar cells and amacrine cells. Release of glutamate activated the presynaptic transporter with a time course that suggested a perisynaptic localization. The transporter was also activated by spillover of glutamate from neighboring rod bipolar cells. By recording from pairs of rod bipolar cells and AII amacrine cells, we demonstrate that activation of the transporter-associated anion current hyperpolarizes the presynaptic terminal and thereby inhibits synaptic transmission by suppressing transmitter release. Given the evidence for presynaptic glutamate transporters, similar mechanisms could be of general importance for transmission in the nervous system.

Amacrine Cells↗

PubMedDate not supplied

The unitary event amplitude of mouse retinal on-cone bipolar cells.

Light-evoked synaptic currents were recorded from on-cone bipolar cells in the mouse retina. Fluctuations in the synaptic current observed during maintained light steps were analyzed in order to estimate the amplitude of the underlying unitary event. The maximal synaptic current variance was 5-fold larger than the maximum expected from fluctuations in the number of active postsynaptic channels. Due to uncertainty in the contribution from channel variance, we calculated a range of values for the unitary event amplitude. The observed variance could be accounted for if 30-39 synaptic sites randomly generated unitary events with a waveform identical to the flash-response, and an amplitude of -3.1 to -2.4 pA. The amplitude is consistent with gating about five mGluR6 channels. The shape of the variance-mean relation suggests that in bright light transmitter release approaches zero, while in darkness transmitter release saturates the postsynaptic response. Thus the on-cone bipolar cell synapse is operating over its entire possible range. If it is assumed that the postsynaptic response saturates when one unitary event occurs per integration time, then a lower bound for the unitary event rate is 18 events/s/synaptic site. If the unitary event is generated by a single synaptic vesicle, the results suggest the total vesicle cycling rate available for encoding the on-cone bipolar cell signal is about 540-700 s(-1).

Animals↗

PubMed2006

Parallel processing in two transmitter microenvironments at the cone photoreceptor synapse.

A cone photoreceptor releases glutamate at ribbons located atop narrow membrane invaginations that empty onto a terminal base. The unique shape of the cone terminal suggests that there are two transmitter microenvironments: within invaginations, where concentrations are high and exposures are brief; and at the base, where concentrations are low and exposure is smoothed by diffusion. Using multicell voltage-clamp recording, we show that different subtypes of Off bipolar cells sample transmitter in two microenvironments. The dendrites of an AMPA receptor-containing cell insert into invaginations and sense rapid fluctuations in glutamate concentration that can lead to transient responses. The dendrites of kainate receptor-containing cells make basal contacts and respond to a smoothed flow of glutamate that produces sustained responses. Signaling at the cone to Off bipolar cell synapse illustrates how transmitter spillover and synapse architecture can combine to produce distinct signals in postsynaptic neurons.

Animals↗

PubMed2006

Long-term neuroretinal full-thickness transplants in a large animal model of severe retinitis pigmentosa.

BACKGROUND: The purpose of this study was to explore neuroretinal transplantation in a large animal model of severe retinitis pigmentosa and to establish graft development, long-term survival, graft-host integration, and effects on the host retina. METHODS: Rhodopsin transgenic pigs, aged 6 months, received in one eye a fetal full-thickness neuroretinal sheet in the subretinal space by means of vitrectomy and retinotomy. Six months postoperatively, eyes were studied in the light microscope and with immunohistochemical markers. Full-field electroretinography (ERG) was performed at 4 and 6 months. RESULTS: Laminated grafts with well-organized photoreceptors, rod bipolar cells, and Müller cells were found in five of six eyes. Neuronal connections between graft and host retina were not seen. In the five eyes containing a graft, the number of surviving rods in the host retina was significantly higher compared with unoperated eyes. The ERG did not reveal any significant difference in b-wave amplitude between operated and control eyes, but the cone-derived response in operated eyes increased significantly from 4 to 6 months while the rod response in control eyes decreased significantly. CONCLUSIONS: Fetal full-thickness neuroretina can be transplanted safely to an eye with severe retinal degeneration. In their major part, the transplants develop a normal laminated morphology and survive for at least 6 months. Graft and host retinal neurons do not form connections. Retinal function in the host is reduced initially by the surgical trauma, but the presence of a well-laminated graft counteracts this effect and rescues rods from degeneration.

Animals↗

PubMed2006

The great escape of glutamate from the depth of presynaptic invaginations.

The basal pole of a cone photoreceptor is in close contact with hundreds of bipolar cell dendrites. The function and properties of these unconventional junctions are a long-standing mystery. In this issue of Neuron, DeVries and colleagues provide compelling evidence that glutamate release from a single quanta can diffuse to distant AMPA/KA receptors on these basal junctions to generate slow mEPSCs.

Animals↗

PubMed2006

Diurnal changes in exocytosis and the number of synaptic ribbons at active zones of an ON-type bipolar cell terminal.

The number and morphology of synaptic ribbons at photoreceptor and bipolar cell terminals has been reported to change on a circadian cycle. Here we sought to determine whether this phenomenon exists at goldfish Mb-type bipolar cell terminals with the aim of exploring the role of ribbons in transmitter release. We examined the physiology and ultrastructure of this terminal around two time points: midday and midnight. Nystatin perforated-patch recordings of membrane capacitance (C(m)) revealed that synaptic vesicle exocytosis evoked by short depolarizations was reduced at night, even though Ca(2+) currents were larger. The efficiency of exocytosis (measured as the DeltaC(m) jump per total Ca(2+) charge influx) was thus significantly lower at night. The paired-pulse ratio remained unchanged, however, suggesting that release probability was not altered. Hence the decreased exocytosis likely reflects a smaller readily releasable vesicle pool at night. Electron microscopy of single sections from intact retinas averaged 65% fewer ribbons at night. Interestingly, the number of active zones did not change from day to night, only the probability of finding a ribbon at an active zone. Additionally, synaptic vesicle halos surrounding the ribbons were more completely filled at night when these on-type bipolar cells are more hyperpolarized. There was no change, however, in the physical dimensions of synaptic ribbons from day to night. These results suggest that the size of the readily releasable vesicle pool and the efficiency of exocytosis are reduced at night when fewer ribbons are present at bipolar cell terminal active zones.

Animals↗

PubMed1993

Melatonin synthesis and circadian tryptophan hydroxylase activity in chicken retina following destruction of serotonin immunoreactive amacrine and bipolar cells by kainic acid.

The neurotoxic excitatory amino acid analog, kainic acid, was used to destroy serotonin-immunoreactive inner retinal neurons, bipolar cells and amacrine cells, in retinas of chickens. Tryptophan hydroxylase activity and melatonin content were examined in the kainic acid-lesioned retinas. Tryptophan hydroxylase activity was present in kainic acid-lesioned retinas and displayed a circadian rhythm. Nocturnal levels of activity in lesioned and control retinas were similar. Melatonin synthesis occurred in kainic acid-lesioned retinas in a diurnal cycle as in normal retinas. Dark-phase melatonin content of kainic acid-lesioned retinas exceeded that of controls. We conclude that most, if not all, circadian tryptophan hydroxylase activity and melatonin synthesis occurs in cells other than the cells that contain most of the serotonin in retina, serotonin-immunoreactive bipolar and amacrine cells.

5-Hydroxytryptophan↗

PubMed2006

The optimal synapse for sparse, binary signals in the rod pathway.

The sparsity of photons at very low light levels necessitates a nonlinear synaptic transfer function between the rod photoreceptors and the rod-bipolar cells. We examine different ways to characterize the performance of the pathway: the error rate, two variants of the mutual information, and the signal-to-noise ratio. Simulation of the pathway shows that these approaches yield substantially different performance at very low light levels and that maximizing the signal-to-noise ratio yields the best performance when judged from simulated images. The results are compared to recent data.

Animals↗

PubMed2006

Requirement for Bhlhb5 in the specification of amacrine and cone bipolar subtypes in mouse retina.

The mammalian retina comprises six major neuronal cell types and one glial type that are further classified into multiple subtypes based on their anatomical and functional differences. Nevertheless, how these subtypes arise remains largely unknown at the molecular level. Here, we demonstrate that the expression of Bhlhb5, a bHLH transcription factor of the Olig family, is tightly associated with the generation of selective GABAergic amacrine and Type 2 OFF-cone bipolar subtypes throughout retinogenesis. Targeted deletion of Bhlhb5 results in a significant reduction in the generation of these selective bipolar and amacrine subtypes. Furthermore, although a Bhlhb5-null mutation has no effect on the expression of bHLH-class retinogenic genes, Bhlhb5 expression overlaps with that of the pan-amacrine factor NeuroD and the expression of Bhlhb5 and NeuroD is negatively regulated by ganglion cell-competence factor Math5. Our results reveal that a bHLH transcription factor cascade is involved in regulating retinal cell differentiation and imply that Bhlhb5 functions downstream of retinogenic factors to specify bipolar and amacrine subtypes.

Amacrine Cells↗