Dopaminergic Modulation of Gap Junction Permeability Between Amacrine Cells in Mammalian Retina

In mammalian retina, the rod bipolar cells synapse on the AII amacrine cells, which are therefore the third-order neurons in the rod-signal pathway. The AII amacrine cells are connected by gap junctions, both to each other and to fourth-order, On-center cone bipolar cells. They also receive synaptic input from the dopaminergic amacrine cells, and in this study, we investigated whether dopamine modulates the permeability of the gap junctions between AII amacrine cells in the isolated rabbit retina. The small biotinylated tracer Neurobiotin was injected into nuclear yellow-labeled AII cells under direct microscopic control. The extent of tracer coupling to neighboring AII cells, 40-60 min after Neurobiotin injection (0.5 nA for 60 sec), provided a standard measure of the permeability of the homologous gap junctions. Under control conditions, individual All amacrine cells were coupled to 73 +/- 15 neighboring cells, and this was unaffected by changes in pH from 6.6 to 7.8. Exogenous dopamine significantly reduced the tracer coupling at concentrations as low as 10 nM (26 +/- 16 cells), with the eff ect increasing with dopamine concentration up to 10 muM (6 +/- 4 cells). The uncoupling effect of dopamine was both blocked by the selective D1 antagonist SCH-23390 (10 muM) and mimicked by the specific D1 agonist SKF-38393 (500 muM). Moreover, the All amacrine cells were also uncoupled when the retina was incubated in forskolin (60 muM) and isobutylmethylxanthine (200 muM). Taken together, these results indicated that the uncoupling was mediated by a D1-like receptor that stimulates cAMP production. Although the selective D1 antagonist on its own did not increase tracer coupling, suggesting that there was little release of endogenous dopamine in the superfused photo-bleached retina, veratridine-evoked release of endogenous transmitters did uncouple the AII amacrine cells, and this effect was blocked by the specific D1 antagonist

Adaptation-Dependent Synchronous Activity Contributes to Receptive Field Size Change of Bullfrog Retinal Ganglion Cell

Nearby retinal ganglion cells of similar functional subtype have a tendency to discharge spikes in synchrony. The synchronized activity is involved in encoding some aspects of visual input. On the other hand, neurons always continuously adjust their activities in adaptation to some features of visual stimulation, including mean ambient light, contrast level, etc. Previous studies on adaptation were primarily focused on single neuronal activity, however, it is also intriguing to investigate the adaptation process in population neuronal activities. In the present study, by using multi-electrode recording system, we simultaneously recorded spike discharges from a group of dimming detectors (OFF-sustained type ganglion cells) in bullfrog retina. The changes in receptive field properties and synchronization strength during contrast adaptation were analyzed. It was found that, when perfused using normal Ringer's solution, single neuronal receptive field size was reduced during contrast adaptation, which was accompanied by weakening in synchronization strength between adjacent neurons' activities. When dopamine (1 µM) was applied, the adaptation-related receptive field area shrinkage and synchronization weakening were both eliminated. The activation of D1 receptor was involved in the adaptation-related modulation of synchronization and receptive field. Our results thus suggest that the size of single neuron's receptive field is positively related to the strength of its synchronized activity with its neighboring neurons, and the dopaminergic pathway is responsible for the modulation of receptive field property and synchronous activity of the ganglion cells during the adaptation process

Heterogeneous Morphology and Tracer Coupling Patterns of Retinal Oligodendrocytes

The present study characterizes the morphology and tracer coupling patterns of oligodendrocytes in the myelinated band of the rabbit retina, as revealed by intracellular injection of biocytin or Lucifer yellow in an isolated superfused preparation. Based on the observed heterogeneity in morphology, we have grouped the presumptive oligodendrocytes into three categories termed 'parallel', 'stratified' and 'radial'. Most parallel oligodendrocytes were tracer coupled to nearby oligodendrocytes and astrocytes, whereas the stratified and radial oligodendrocytes rarely showed coupling. We conclude that the different categories of oligodendrocytes may be stages in a developmental series, with radial oligodendrocytes being premyelinating cells, parallel oligodendrocytes being mature myelinating cells and the stratified cells representing a transition between these categories

Ph-Gated Dopaminergic Modulation of Horizontal Cell Gap-Junctions in Mammalian Retina

Horizontal cells mediate lateral inhibition in the outer retina, and this process is dependent on electrical coupling through gap junctions, giving rise to receptive fields that are much wider than the dendritic fields. This study on rabbit retina shows that the permeability of the gap junctions between A-type horizontal cells, as assessed by Lucifer yellow dye coupling, is modulated by dopamine through a D-1 receptor linked to adenylate cyclase. Both exogenously applied dopamine and endogenously released dopamine uncoupled the horizontal cells, but the effect was pH-gated whereby it occurred only at an extracellular pH 7.2 +/- 0.05. The horizontal cells also uncoupled in acidic media (pH 7.0 or below) in the absence of dopamine. Our results show that horizontal cell coupling in the mammalian retina is regulated by both dopamine and pH. Given that the pH in the outer retina varies with the metabolic activity of the photoreceptors, these results suggest that ambient light conditions could gate the activity of neurotransmitters through pH-sensitive mechanisms

Efficacy of Single or Repeated Hemoperfusion in a Canine Model of Paraquat Poisoning

Although hemoperfusion has been used to treat paraquat poisoning, its efficacy has been widely debated. This study examines the kinetic and pathologic correlates of paraquat toxicity and hemoperfusion and the efficacy of hemoperfusion in four groups of four dogs. This species was chosen because the kinetics and toxicity of paraquat are similar to those in the human. All dogs given a lethal dose of paraquat dichloride producing 100% mortality as a 2-hr infusion (7.48 mg of paraquat ion per kg) developed the typical clinical, laboratory and pathologic features of paraquat toxicity and died within 5 to 7 days. All dogs given paraquat and hemoperfused for 8 hr daily, beginning at 12 hr, died within 3 to 6 days. Two of four dogs which were hemoperfused once, beginning at 2 hr, survived. One dog in the repeated hemoperfusion only group died from blood loss. Negligible amounts of paraquat (0.4-2.0% of the total dose) were adsorbed during repeated hemoperfusion because of extensive excretion of paraquat in urine and sequestration in peripheral tissues from which redistribution was slow. The efficacy in the single early hemoperfusion group can be attributed to removal of 25% of the dose by the procedure in the two survivors. We conclude that single hemoperfusion may have some clinical application in patients who present within a few hours of the ingestion and have not ingested a dose of paraquat that is multiples of the lethal dose producing 100% mortality. It is doubtful if there is any role for repeated hemoperfusion

Effects of Paraquat On Canine Bronchoalveolar Lavage Fluid

Bronchoalveolar lavage (BAL) recovers the epithelial lung fluid of the lower respiratory tract. In this study, we have used BAL to detect early pulmonary injury in beagle dogs following an intravenous infusion of 10 mg paraquat dichloride/kg bodyweight. Bronchoalveolar lavage was performed twice in 11 dogs, 60 hr before and 34 hr after an intravenous infusion of paraquat dichloride (n = 8) or saline (n = 3). The dogs were studied in three groups: (1) paraquat only (n = 4); (2) paraquat plus hemoperfusion (n = 4); and (3) hemoperfusion only (n = 3). Because hemoperfusion, a treatment used for paraquat poisoning, could have effects on BAL independent of paraquat, we evaluated the effects on BAL fluid of this procedure performed separately from and together with administration of paraquat. We examined cytology, proteins, enzymes, and glutathione in the BAL fluid and expressed all results per milliliter of aspirated lavage fluid. Hemoperfusion did not alter the BAL fluid. In contrast, in dogs studied 34 hr after administration of paraquat, total cell counts, alveolar macrophage and neutrophil counts, and concentrations of total protein, albumin, ACE, LDH, and ALP were increased. Bronchoalveolar lavage in the dog provides an excellent tool with which to detect early paraquat-induced pulmonary injury. The same technique could be useful for sequential monitoring of other types of pulmonary disease and injury

Primary glaucoma in Burmese cats

Objective To document the clinical signs and management of primary glaucoma in Burmese cats