The AII Amacrine Network: Coupling can Increase Correlated Activity

Retinal ganglion cells in the cat respond to single rhodopsin isomerizations with one to three spikes. This quantal signal is transmitted in the retina by the rod bipolar pathway: rod→rod bipolar→AII→cone bipolar→ganglion cell. The two-dimensional circuit underlying this pathway includes extensive convergence from rods to an AII amacrine cell, divergence from a rod to several AII and ganglion cells, and coupling between the AII amacrine cells. In this study we explored the function of coupling by reconstructing several AII amacrine cells and the gap junctions between them from electron micrographs; and simulating the AII network with and without coupling. The simulation showed that coupling in the AII network can: (1) improve the signal/noise ratio in the AII network; (2) improve the signal/noise ratio for a single rhodopsin isomerization striking in the periphery of the ganglion cell receptive field center, and therefore in most ganglion cells responding to a single isomerization; (3) expand the AII and ganglion cells' receptive field center; and (4) expand the “correlation field”. All of these effects have one major outcome: an increase in correlation between ganglion cell activity. Well correlated activity between the ganglion cells could improve the brain's ability to discriminate few absorbed external photons from the high background of spontaneous thermal isomerizations. Based on the possible benefits of coupling in the AII network, we suggest that coupling occurs at low scotopic luminances. Copyright © 1996 Elsevier Science Ltd.     

Intrinsic properties and functional circuitry of the AII amacrine cell

Amacrine cells represent the most diverse class of retinal neuron, comprising dozens of distinct cell types. Each type exhibits a unique morphology and generates specific visual computations through its synapses with a subset of excitatory interneurons (bipolar cells), other amacrine cells, and output neurons (ganglion cells). Here, we review the intrinsic and network properties that underlie the function of the most common amacrine cell in the mammalian retina, the AII amacrine cell. The AII connects rod and cone photoreceptor pathways, forming an essential link in the circuit for rod-mediated (scotopic) vision. As such, the AII has become known as the rod-amacrine cell. We, however, now understand that AII function extends to cone-mediated (photopic) vision, and AII function in scotopic and photopic conditions utilizes the same underlying circuit: AIIs are electrically coupled to each other and to the terminals of some types of ON cone bipolar cells. The direction of signal flow, however, varies with illumination. Under photopic conditions, the AII network constitutes a crossover inhibition pathway that allows ON signals to inhibit OFF ganglion cells and contributes to motion sensitivity in certain ganglion cell types. We discuss how the AII's combination of intrinsic and network properties accounts for its unique role in visual processing.     

Function and plasticity of homologous coupling between AII amacrine cells

The AII amacrine cells are critical elements in the primary rod pathway of the mammalian retina, acting as an obligatory conduit of rod signals to both on- and off-center ganglion cells. In addition to the chemical synaptic circuitry they subserve, AII cells form two types of electrical synapses corresponding to gap junctions formed between neighboring AII cells as well as junctions formed between AII cells and on-center cone bipolar cells. Our recent results indicate that coupling between AII cells and cone bipolar cells forms an obligatory synapse for transmission of scotopic visual signals to on-center ganglion cells. In contrast, AII-AII cell coupling acts to maintain the sensitivity of the primary rod pathway by allowing for summation of synchronous activity and the attenuation of asynchronous background noise. Further, the conductance of AII-AII cell gap junctions is highly dynamic, regulated by ambient light conditions, thereby preserving the fidelity of rod signaling over the scotopic operating range from starlight to twilight.     

Gap junctions between AII amacrine cells and calbindin-positive bipolar cells in the rabbit retina

Electrical synapses or gap junctions occur between many retinal neurons. However, in most cases, the gap junctions have not been visualized directly. Instead, their presence has been inferred from tracer spread throughout the network of cells. Thus, tracer coupling is taken as a marker for the presence of gap junctions between coupled cells. AII amacrine cells are critical interneurons in the rod pathway of the mammalian retina. Rod bipolar cell output passes to AII amacrine cells, which in turn make conventional synapses with OFF cone bipolar cells and gap junctions with ON cone bipolar cells. Injections of biotinylated tracers into AII amacrine cells reveals coupling between the AII amacrine cell network and heterologous coupling with a variety of ON cone bipolar cells, including the calbindin-positive cone bipolar cell. To directly visualize gap junctions in this network, we prepared material for electron microscopy that was double labeled with antibodies to calretinin and calbindin to label AII amacrine cells and calbindin-positive cone bipolar cells, respectively. AII amacrine cells were postsynaptic to large vesicle-laden rod bipolar terminals, as previously reported. Gap junctions were identified between AII amacrine cells and calbindin-positive cone bipolar cell terminals identified by the presence of immunostaining and ribbon synapses. This represents direct confirmation of gap junctions between two different yet positively identified cells, which are tracer coupled, and provides additional evidence that tracer coupling with Neurobiotin indicates the presence of gap junctions. These results also definitively establish the presence of gap junctions between AII amacrine cells and calbindin bipolar cells which can therefore carry rod signals to the ON alpha ganglion cell.     

Mechanism and site of action of a dopamine D1 antagonist in the rabbit retina

Dopamine D1 antagonists have been shown to alter drastically the spontaneous and light-evoked activity of ganglion cells in the rabbit retina (Jensen & Daw, 1984, 1986). A major target of dopaminergic neurons in mammalian retinas appears to be rod AII amacrine cells (Pourcho, 1982; Voigt & W?ssle, 1987). In the present study, the following questions were addressed: (1) Do dopamine D1 antagonists alter the activity of ganglion cells through actions primarily on rod AII amacrine cells? (2) Are the effects of dopamine D1 antagonists on ganglion cells due to an inhibition of dopamine-stimulated adenylate cyclase activity? Using an isolated, superfused retinal preparation, the ability of several pharmacological agents to counteract the physiological effects of the dopamine D1 antagonist (+)-SCH 23390 on rabbit ganglion cells was examined. The glycine antagonist strychnine abolished the effects of (+)-SCH 23390 on the spontaneous and light-evoked activity of OFF-center ganglion cells, whereas the excitatory amino-acid antagonist kynurenic acid abolished the effects of (+)-SCH 23390 on the spontaneous and light-evoked activity of ON-center ganglion cells. The findings obtained with these antagonists can be explained in terms of the known synaptic connections of AII amacrine cells. Both 8-(4-chlorophenylthio) cyclic AMP, a membrane-permeable cAMP analog, and forskolin, an activator of adenylate cyclase, reversed the effects of (+)-SCH 23390 on the spontaneous and light-evoked activity of OFF-center ganglion cells but not ON-center ganglion cells. These findings suggest that the effects of dopamine D1 antagonists on OFF-center ganglion cells are due to an inhibition of dopamine-stimulated adenylate cyclase, with the ensuing lowering of cellular cAMP levels. The effects of dopamine D1 antagonists on ON-center ganglion cells appear, however, to be independent of intracellular cAMP levels.     

AII amacrine cells express the MT1 melatonin receptor in human and macaque retina

AII amacrine cells are critical interneurons in the rod pathway of mammalian retina, active primarily in dim lighting conditions. Melatonin, a neuromodulator produced at night in the retina, is believed to induce retinal adaptation to dim lighting conditions in most vertebrate species examined to date, including humans. We hypothesized that melatonin may influence retinal light adaptation by acting on AII cells directly and thus investigated whether melatonin receptors were expressed in AII neurons. Postmortem nonpathological eyes from four human donors as well as two eyes from two Macaque Fasicularis monkeys were analyzed. Double immunocytochemistry was performed using an anti-MT(1) antibody and an antibody to calretinin, an AII marker. Analysis utilized confocal microscopy. A polyclonal anti-calretinin antibody labelled amacrine cells exhibiting the distinct AII morphology, in both human and macaque retina. MT(1) immunoreactivity in macaque retina was similar to human staining, in that horizontal, amacrine and ganglion cell bodies were stained, as were inner segments of photoreceptors. In human retina 86% of calretinin positive cells expressed the MT(1) receptor peripherally, whereas centrally, 78% colocalization was observed. In the macaque retina, 100% of AII amacrine cells expressed MT(1) immunoreactivity both centrally and peripherally. That virtually all AII neurons express the MT(1) receptor in both human and macaque retina, may provide the first evidence demonstrating a role for melatonin in AII regulation, furthering the hypothesis of melatonin function in retinal light adaptation.     

AMPA-selective glutamate receptor subunits GluR2 and GluR4 in the cat retina: an immunocytochemical study

AMPA-selective glutamate receptors play a major role in glutamatergic neurotransmission in the retina and are expressed in a variety of neuronal subpopulations. In the present study, immunocytochemical techniques were used to visualize the distribution of GluR2 and GluR4 subunits in the cat retina. Results were compared with previous localizations of GluR1 and GluR2/3. Staining for GluR2 was limited to a small number of amacrine and ganglion cells whereas GluR4 staining was present in A-type horizontal cells, many amacrine cells including type AII amacrine cells, and the majority of the cells in the ganglion cell layer. Analysis of synaptic relationships in the outer plexiform layer showed the GluR4 subunit to be concentrated at the contacts of cone photoreceptors with A-horizontal cells. In the inner plexiform layer, both GluR2 and GluR4 were postsynaptic to cone bipolar cells at dyad contacts although GluR2 staining was limited to one of the postsynaptic elements whereas GluR4 immunoreactivity was often seen in both postsynaptic elements. Unlike GluR2, GluR4 was also postsynaptic to rod bipolar cells where it could be visualized in processes of AII amacrine cells. The data indicate that GluR3 and GluR4 subunits are colocalized in a number of cell types including A-type horizontal cells, AII amacrine cells, and alpha ganglion cells, but whether they are combined in the same multimeric receptors remains to be determined.     

Expression of brain-derived neurotrophic factor in cholinergic and dopaminergic amacrine cells in the rat retina and the effects of constant light rearing

Brain-derived neurotrophic factor (BDNF) regulates many aspects of neuronal development, including survival, axonal and dendritic growth and synapse formation. Despite recent advances in our understanding of the functional significance of BDNF in retinal development, the retinal cell types expressing BDNF remains poorly defined. The goal of the present study was to determine the localization of BDNF in the mammalian retina, with special focus on the subtypes of amacrine cells, and to characterize, at the cellular level, the effects of constant light exposure during early postnatal period on retinal expression of BDNF. Retinas from 3-week-old rats reared in a normal light cycle or constant light were subjected to double immunofluorescence staining using antibodies to BDNF and retinal cell markers. BDNF immunoreactivity was localized to ganglion cells, cholinergic amacrine cells and dopaminergic amacrine cells, but not to AII amacrine cells regardless of rearing conditions. Approximately 75% of BDNF-positive cells in the inner nuclear layer were cholinergic amacrine cells in animals reared in a normal lighting condition. While BDNF immunoreactivity in ganglion cells and cholinergic amacrine cells was significantly increased by constant light rearing, which in dopaminergic amacrine cells was apparently unaltered. The overall structure of the retina and the density of ganglion cells, cholinergic amacrine cells and AII amacrine cells were unaffected by rearing conditions, whereas the density of dopaminergic amacrine cells was significantly increased by constant light rearing. The present results indicate that cholinergic amacrine cells are the primary source of BDNF in the inner nuclear layer of the rat retina and provide the first evidence that cholinergic amacrine cells may be involved in the visual activity-dependent regulation of retinal development through the production of BDNF. The present data also suggest that the production or survival of dopaminergic amacrine cells is regulated by early visual experience.     

Rod pathways in the retina of the cat

Neurons involved in the transfer of rod signals to the ganglion cells in the retina of the cat have been recorded from and stained with horseradish peroxidase (HRP) and their synaptic connections determined by electron microscopy. The single morphological type of rod bipolar cell responds with a sustained hyperpolarization to light and in turn drives at least five morphologically different types of amacrine cells, each of which has a unique response pattern. Two amacrines respond with either a transient (AII) or a sustained (A17) depolarization to light, while three amacrines give transient (A8) or sustained (A6, A13) hyperpolarizations. Circuitry whereby rod signals reach both on-centre and off-centre ganglion cells is discussed.     

Localization of AMPA-selective glutamate receptor subunits in the cat retina: a light- and electron-microscopic study

The distribution of AMPA-selective glutamate receptor subunits was studied in the cat retina using antisera against GluR1 and GluR2/3. Both antisera were localized in postsynaptic sites in the outer plexiform layer (OPL) as well as the inner plexiform layer (IPL). Immunoreactivity for GluR1 was seen in a subpopulation of OFF cone bipolar cells and a number of amacrine and ganglion cells. Within the IPL, processes staining for GluR1 received input from OFF and ON cone bipolar cells but not from rod bipolars. Labeling for GluR2/3 was seen in horizontal cells, an occasional cone bipolar cell, and numerous amacrine and ganglion cells. In the IPL, GluR2/3 staining was postsynaptic to cone bipolar cells in both sublaminae. AII amacrine cells which receive rod bipolar input were also labeled for GluR2/3. With both antisera, staining was limited to a single member of the bipolar dyad complex, providing morphological evidence for functional diversity in glutamatergic pathways.     

On and off pathways through amacrine cells in mammalian retina: the synaptic connections of "starburst" amacrine cells

The neural architecture of on and off pathways in mammalian retina is described, including the development of ideas leading to an understanding of the bisublaminar organization of the inner plexiform layer of the retina which supports these two pathways. The complexities of bipolar cell contributions are contrasted with the relative simplicity of ganglion cell organization with regard to bisublaminar architecture, and a key role is described for internuncial amacrine cells as specific targets for bipolar cells. Two very different kinds of amacrine cell are considered and compared, both of which mediate bipolar input to ganglion cells. These are the rod (type II) amacrine cell, and the more recently discovered "starburst" amacrine cell, which is apparently cholinergic in function. As different as the wide-field starburst amacrine cells are from the narrow-field rod amacrine cells, they share important features. Both are interposed between bipolar and ganglion cells, and both have segregated regions of presynaptic boutons. They differ, however, in that rod amacrines may perform more specific functions related to receptive field center organization, while the functional role of starburst amacrines may be unrelated to receptive field properties of ganglion cells. The mirror-symmetry of type a and type b (off and on) starburst amacrine cells is described together with their synaptic circuitry. In contrast to the rod amacrine cell the output of starburst amacrines is exclusively to ganglion cells. Others have proposed a dual function for acetylcholine (ACh) in the retina. A unifying hypothesis is briefly sketched here which relates the pharmacology of ACh and the dendritic stratification of starburst amacrine cells to the form and function of ganglion cells. It is proposed that the amount of generalized synaptic excitation received from ACh/starburst amacrine cells by a particular type of ganglion cell is largely a function of co-stratification of the ganglion cell's dendrites with the distal boutons of starburst amacrine cells.     

Synaptic patterns and response properties of bipolar and ganglion cells in the cat retina

After intracellular recording, bipolar cells of the cat retina have been stained with HRP and their contacts in the outer and inner plexiform layers examined by electron microscopy. Rod bipolars and cone bipolar cb6 make invaginating, ribbon related contacts with photoreceptors, hyperpolarize in response to light, and have axons terminating in layer b of the IPL. The axon terminal of cb2 ends in layer a of the IPL and its basal contacts with cones mediate hyperpolarizing light-responses. Cone bipolar cb5 is a center-depolarizing type with an axon ending in layer b but its cone contacts are at semi-invaginating basal junctions. Except for the amacrine-contacting rod bipolar cell, all cone bipolar types synapse with both amacrine and ganglion cells in the inner plexiform layer. In addition cb5 contacts AII amacrine cells with large gap junctions, and is physiologically rod dominated.     

The rod circuit in the rabbit retina

Mammalian retinae have a well-defined neuronal pathway that serves rod vision. In rabbit retina, the different populations of interneurons in the rod pathway can be selectively labeled, either separately or in combination. The rod bipolar cells show protein kinase C immunoreactivity; the rod (AII) amacrine cells can be distinguished in nuclear-yellow labeled retina; the rod reciprocal (S1 & S2) amacrine cells accumulate serotonin; and the dopaminergic amacrine cells show tyrosine-hydroxylase immunoreactivity. Furthermore, intracellular dye injection of the microscopically identified interneurons enables whole-population and single-cell studies to be combined in the same tissue. Using this approach, we have been able to analyze systematically the neuronal architecture of the rod circuit across the rabbit retina and compare its organization with that of the rod circuit in central cat retina. In rabbit retina, the rod interneurons are not organized in a uniform neuronal module that is simply scaled up from central to peripheral retina. Moreover, peripheral fields in superior and inferior retina that have equivalent densities of each neuronal type show markedly different rod bipolar to AII amacrine convergence ratios, with the result that many more rod photoreceptors converge on an AII amacrine cell in superior retina. In rabbit retina, much of the convergence in the rod circuit occurs in the outer retina whereas, in central cat retina, it is more evenly distributed between the inner and outer retina.     

All amacrine cells in the rabbit retina possess AMPA-, NMDA-, GABA-, and glycine-activated currents

Physiological properties of ligand-activated currents were characterized for morphologically identified AII amacrine cells in the rabbit retina by using whole-cell recordings in a superfused retina slice preparation. The AII amacrine cells were identified based on their distinct narrow-field, bistratified morphology. In the present study, the whole-cell recordings from AII amacrine cells synaptically isolated from presynaptic influences demonstrated the presence of glutamate AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid) receptors, but no kainate receptors. The presence of only AMPA receptors on rabbit AII amacrine cells is in contrast to an earlier study on rabbit AII amacrine cells by Bloomfield and Xin (2000), but consistent with previous studies on rat AII amacrine cells. In addition, NMDA (N-methyl-D-aspartate) -activated currents blocked by the NMDA antagonist D-AP7 (D-2-amino-7-phosphonoheptanoic acid) were found on the AII amacrine cells. These most likely extrasynaptic NMDA-activated currents were attenuated by the presence of Co2+ interacting with Mg2+ and Ca2+ as they competed for divalent cation-binding sites within the NMDA channel. AII amacrine cells also possessed GABA (gamma-aminobutyric acid) -activated currents that were unaffected by the GABAc receptor antagonist TPMPA (1,2,5,6-tetrahydropyridine-4-yl methylphosphinic), but were completely blocked by the GABA(A) antagonist bicuculline. This indicates that the major inhibitory inputs were mediated by only GABA(A) receptors located directly on the AII amacrine cells. Furthermore, although the AII amacrine cells were glycinergic amacrine cells, they also possessed glycine-activated currents that may be mediated by autoreceptors.     

Morphological and physiological properties of the A17 amacrine cell of the rat retina

In addition to the well-studied AII amacrine cell, there is another amacrine cell type participating in the rod pathway of the mammalian retina. In cat, this cell is called the A17 amacrine cell, and in rabbits, it is called the indoleamine-accumulating amacrine cell (S1 and S2); however, the presence of the corresponding cell type has not yet been described in detail for the rat retina. To this end, we injected amacrine cells with Neurobiotin in vertical retinal slices. After histological processing, we were able to reconstruct the morphology of a wide-field amacrine cell which showed characteristics of A17 and S1/S2 amacrine cells. The rat wide-field amacrine cells exhibited the same stratification pattern, their dendrites bore varicosities and ramified in sublamina 5 of the inner plexiform layer (IPL), and they were dye-coupled to other amacrine cells. To determine whether those amacrine cells shared electrophysiological characteristics as well, we performed whole-cell patch-clamp recordings and examined their voltage-activated currents and neurotransmitter-induced currents. We never observed voltage-gated Na+ currents and spike-like potentials upon depolarization by current injection in these cells. We identified GABA- and glycine-sensitive Cl- currents that could be blocked by bicuculline and strychnine, respectively. We also observed kainate- and AMPA-activated currents, which could be inhibited by the application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Finally, a 400-ms full-field light stimulus was used to characterize the light responses of A17 amacrine cells. The light ON-induced inward current could be suppressed by the application of 2,3-Dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulphonamide (NBQX), while the majority of the light OFF-induced current was inhibited by bicuculline and reduced to a smaller extent by NBQX. CPP, an NMDA blocker, had no effect on the light response of rat A17 amacrine cells.     

Hedgehog信号通路在视网膜细胞发育及病理性血管生成中的作用

视网膜细胞发育障碍和眼部血管的病理性生长可见于多种眼部疾病,严重影响患者视力.Hedgehog信号转导通路已被证实参与视网膜神经节细胞、无长突细胞、视锥细胞、视杆细胞、Müller胶质细胞、视网膜色素上皮(RPE)细胞等细胞生长发育的多个过程.近年来研究表明,Hedgehog信号通路可以调控视网膜细胞的分化和发育,并在眼部新生血管生成中起到关键性作用.本文从Hedgehog信号通路的组成、Hedgehog信号通路与视网膜细胞发育、视网膜再生、Hedgehog信号通路与眼部病理性血管生成4个方面就Hedgehog信号通路在视网膜细胞发育及病理性血管生成中的作用进行综述,以期为视网膜及眼部血管性疾病的治疗提供新的靶点.     

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

Differential cellular and subcellular distribution of glutamate transporters in the cat retina

Retrieval of glutamate from extracellular sites in the retina involves at least five excitatory amino acid transporters. Immunocytochemical analysis of the cat retina indicates that each of these transporters exhibits a selective distribution which may reflect its specific function. The uptake of glutamate into Muller cells or astrocytes appears to depend upon GLAST and EAAT4, respectively. Staining for EAAT4 was also seen in the pigment epithelium. The remaining transporters are neuronal with GLT-1alpha localized to a number of cone bipolar, amacrine, and ganglion cells and GLT-1v in cone photoreceptors and several populations of bipolar cells. The EAAC1 transporter was found in horizontal, amacrine, and ganglion cells. Staining for EAAT5 was seen in the axon terminals of both rod and cone photoreceptors as well as in numerous amacrine and ganglion cells. Although some of the glutamate transporter molecules are positioned for presynaptic or postsynaptic uptake at glutamatergic synapses, others with localizations more distant from such contacts may serve in modulatory roles or provide protection against excitoxic or oxidative damage.     

Neural reprogramming in retinal degeneration

PURPOSE: Early visual defects in degenerative diseases such as retinitis pigmentosa (RP) may arise from phased remodeling of the neural retina. The authors sought to explore the functional expression of ionotropic (iGluR) and group 3, type 6 metabotropic (mGluR6) glutamate receptors in late-stage photoreceptor degeneration. METHODS: Excitation mapping with organic cations and computational molecular phenotyping were used to determine whether retinal neurons displayed functional glutamate receptor signaling in rodent models of retinal degeneration and a sample of human RP. RESULTS: After photoreceptor loss in rodent models of RP, bipolar cells lose mGluR6 and iGluR glutamate-activated currents, whereas amacrine and ganglion cells retain iGluR-mediated responsivity. Paradoxically, amacrine and ganglion cells show spontaneous iGluR signals in vivo even though bipolar cells lack glutamate-coupled depolarization mechanisms. Cone survival can rescue iGluR expression by OFF bipolar cells. In a case of human RP with cone sparing, iGluR signaling appeared intact, but the number of bipolar cells expressing functional iGluRs was double that of normal retina. CONCLUSIONS: RP triggers permanent loss of bipolar cell glutamate receptor expression, though spontaneous iGluR-mediated signaling by amacrine and ganglion cells implies that such truncated bipolar cells still release glutamate in response to some nonglutamatergic depolarization. Focal cone-sparing can preserve iGluR display by nearby bipolar cells, which may facilitate late RP photoreceptor transplantation attempts. An instance of human RP provides evidence that rod bipolar cell dendrite switching likely triggers new gene expression patterns and may impair cone pathway function.     

Distribution of protein kinase C isoforms in the cat retina

Immunocytochemical localization was carried out for five isoforms of protein kinase C (PKC) in the cat retina. In common with other mammalian species, PKCalpha 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). PKCbetaI was localized to rod bipolar cells, one class of cone bipolar cell, and numerous amacrine and displaced amacrine cells. Staining for PKCbetaI was seen in three types of cone bipolar cells as well as in amacrine and ganglion cells. Immunoreactivity for both PKCepsilon and PKCzeta was found in rod bipolar cells; PKCepsilon was also seen in a population of cone bipolar cells and a few amacrine and ganglion cells whereas PKCzeta was found in all ganglion cells. Double-label immunofluorescence studies showed that dendrites of the two PKCbetaII-positive OFF-cone bipolar cells exhibit immmunoreactivity for the kainate-selective glutamate receptor GluR5. The third PKCbetaII 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.