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Effects of Dopamine D2-Like Receptor Antagonists on Light Responses of Ganglion Cells in Wild-Type and P23H Rat Retinas.

Jensen R - PLoS ONE (2015)

Bottom Line: In addition, L-745,870, but not sulpiride or eticlopride, reduced the maximum peak responses of Sprague-Dawley rat RGCs.Both sulpiride and eticlopride, but not L-745,870, reduced this ON response and brought out a short-latency OFF response, suggesting that these cells are in actuality OFF-center cells.Overall, the results show that the altered dopaminergic system in degenerate retinas contributes to the deteriorated light responses of RGCs.

View Article: PubMed Central - PubMed

Affiliation: VA Boston Healthcare System, Mail Stop 151E, 150 South Huntington Avenue, Boston, Massachusetts 02130, United States of America.

ABSTRACT
In animal models of retinitis pigmentosa the dopaminergic system in the retina appears to be dysfunctional, which may contribute to the debilitated sight experienced by retinitis pigmentosa patients. Since dopamine D2-like receptors are known to modulate the activity of dopaminergic neurons, I examined the effects of dopamine D2-like receptor antagonists on the light responses of retinal ganglion cells (RGCs) in the P23H rat model of retinitis pigmentosa. Extracellular electrical recordings were made from RGCs in isolated transgenic P23H rat retinas and wild-type Sprague-Dawley rat retinas. Intensity-response curves to flashes of light were evaluated prior to and during bath application of a dopamine D2-like receptor antagonist. The dopamine D2/D3 receptor antagonists sulpiride and eticlopride and the D4 receptor antagonist L-745,870 increased light sensitivity of P23H rat RGCs but decreased light sensitivity in Sprague-Dawley rat RGCs. In addition, L-745,870, but not sulpiride or eticlopride, reduced the maximum peak responses of Sprague-Dawley rat RGCs. I describe for the first time ON-center RGCs in P23H rats that exhibit an abnormally long-latency (>200 ms) response to the onset of a small spot of light. Both sulpiride and eticlopride, but not L-745,870, reduced this ON response and brought out a short-latency OFF response, suggesting that these cells are in actuality OFF-center cells. Overall, the results show that the altered dopaminergic system in degenerate retinas contributes to the deteriorated light responses of RGCs.

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Effects of dopamine D2-like receptor antagonists on light responses of long-latency ON-center P23H rat RGCs.Displayed are spike rasters and PSTHs of spike activity recorded from three RGCs to stimulation with a small spot of light centered over the receptive field. The D2/D3 receptor antagonists sulpiride (panel A) and eticlopride (panel B) eliminated the ON responses (indicated by arrows) and brought out OFF responses. The D4 receptor antagonist L-745,870 (panel C) had very little effect on the light response. Blue horizontal bars indicate the duration of the light stimulus.
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pone.0146154.g006: Effects of dopamine D2-like receptor antagonists on light responses of long-latency ON-center P23H rat RGCs.Displayed are spike rasters and PSTHs of spike activity recorded from three RGCs to stimulation with a small spot of light centered over the receptive field. The D2/D3 receptor antagonists sulpiride (panel A) and eticlopride (panel B) eliminated the ON responses (indicated by arrows) and brought out OFF responses. The D4 receptor antagonist L-745,870 (panel C) had very little effect on the light response. Blue horizontal bars indicate the duration of the light stimulus.

Mentions: Of the 9 long-latency ON-center RGCs, 3 cells were tested with sulpiride, 3 cells were tested with eticlopride, and 3 cells were tested with L-745,870. For the cells that were examined with the D2/D3 receptor antagonists sulpiride and eticlopride, the long-latency ON responses (calculated with a 200-ms window encompassing the peak activity and subtracting the pre-stimulus spontaneous activity) to a small spot of light were significantly reduced (from 30.5 ± 12.2 to 4.5 ± 7.5 spikes/s, P = 0.009, n = 6). Along with this reduction in the ON response, a short-latency (95.0 ± 12.3 ms) OFF response appeared in all 6 cells. This OFF response (calculated with a 200-ms window encompassing the peak activity and subtracting the pre-stimulus spontaneous activity) varied from 25 to 94 spikes/s (mean, 48.5 spikes/s). Fig 6A and 6B show the light responses of one long-latency ON-center RGC that was treated with sulpiride and another long-latency ON-center RGC that was treated with eticlopride. In both cases, the ON response disappeared while an OFF response appeared. Neither sulpiride nor eticlopride brought out an OFF response in short-latency ON-center P23H rat RGCs (data not shown). For the 3 cells that were tested with the D4 receptor antagonist L-745,870, the ON response persisted (29.3 ± 2.5 spikes/s in control versus 29.0 ± 9.5 spikes/s in the presence of L-745,870, P = 0.910). This is illustrated for one long-latency ON-center RGC in Fig 6C.


Effects of Dopamine D2-Like Receptor Antagonists on Light Responses of Ganglion Cells in Wild-Type and P23H Rat Retinas.

Jensen R - PLoS ONE (2015)

Effects of dopamine D2-like receptor antagonists on light responses of long-latency ON-center P23H rat RGCs.Displayed are spike rasters and PSTHs of spike activity recorded from three RGCs to stimulation with a small spot of light centered over the receptive field. The D2/D3 receptor antagonists sulpiride (panel A) and eticlopride (panel B) eliminated the ON responses (indicated by arrows) and brought out OFF responses. The D4 receptor antagonist L-745,870 (panel C) had very little effect on the light response. Blue horizontal bars indicate the duration of the light stimulus.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4696741&req=5

pone.0146154.g006: Effects of dopamine D2-like receptor antagonists on light responses of long-latency ON-center P23H rat RGCs.Displayed are spike rasters and PSTHs of spike activity recorded from three RGCs to stimulation with a small spot of light centered over the receptive field. The D2/D3 receptor antagonists sulpiride (panel A) and eticlopride (panel B) eliminated the ON responses (indicated by arrows) and brought out OFF responses. The D4 receptor antagonist L-745,870 (panel C) had very little effect on the light response. Blue horizontal bars indicate the duration of the light stimulus.
Mentions: Of the 9 long-latency ON-center RGCs, 3 cells were tested with sulpiride, 3 cells were tested with eticlopride, and 3 cells were tested with L-745,870. For the cells that were examined with the D2/D3 receptor antagonists sulpiride and eticlopride, the long-latency ON responses (calculated with a 200-ms window encompassing the peak activity and subtracting the pre-stimulus spontaneous activity) to a small spot of light were significantly reduced (from 30.5 ± 12.2 to 4.5 ± 7.5 spikes/s, P = 0.009, n = 6). Along with this reduction in the ON response, a short-latency (95.0 ± 12.3 ms) OFF response appeared in all 6 cells. This OFF response (calculated with a 200-ms window encompassing the peak activity and subtracting the pre-stimulus spontaneous activity) varied from 25 to 94 spikes/s (mean, 48.5 spikes/s). Fig 6A and 6B show the light responses of one long-latency ON-center RGC that was treated with sulpiride and another long-latency ON-center RGC that was treated with eticlopride. In both cases, the ON response disappeared while an OFF response appeared. Neither sulpiride nor eticlopride brought out an OFF response in short-latency ON-center P23H rat RGCs (data not shown). For the 3 cells that were tested with the D4 receptor antagonist L-745,870, the ON response persisted (29.3 ± 2.5 spikes/s in control versus 29.0 ± 9.5 spikes/s in the presence of L-745,870, P = 0.910). This is illustrated for one long-latency ON-center RGC in Fig 6C.

Bottom Line: In addition, L-745,870, but not sulpiride or eticlopride, reduced the maximum peak responses of Sprague-Dawley rat RGCs.Both sulpiride and eticlopride, but not L-745,870, reduced this ON response and brought out a short-latency OFF response, suggesting that these cells are in actuality OFF-center cells.Overall, the results show that the altered dopaminergic system in degenerate retinas contributes to the deteriorated light responses of RGCs.

View Article: PubMed Central - PubMed

Affiliation: VA Boston Healthcare System, Mail Stop 151E, 150 South Huntington Avenue, Boston, Massachusetts 02130, United States of America.

ABSTRACT
In animal models of retinitis pigmentosa the dopaminergic system in the retina appears to be dysfunctional, which may contribute to the debilitated sight experienced by retinitis pigmentosa patients. Since dopamine D2-like receptors are known to modulate the activity of dopaminergic neurons, I examined the effects of dopamine D2-like receptor antagonists on the light responses of retinal ganglion cells (RGCs) in the P23H rat model of retinitis pigmentosa. Extracellular electrical recordings were made from RGCs in isolated transgenic P23H rat retinas and wild-type Sprague-Dawley rat retinas. Intensity-response curves to flashes of light were evaluated prior to and during bath application of a dopamine D2-like receptor antagonist. The dopamine D2/D3 receptor antagonists sulpiride and eticlopride and the D4 receptor antagonist L-745,870 increased light sensitivity of P23H rat RGCs but decreased light sensitivity in Sprague-Dawley rat RGCs. In addition, L-745,870, but not sulpiride or eticlopride, reduced the maximum peak responses of Sprague-Dawley rat RGCs. I describe for the first time ON-center RGCs in P23H rats that exhibit an abnormally long-latency (>200 ms) response to the onset of a small spot of light. Both sulpiride and eticlopride, but not L-745,870, reduced this ON response and brought out a short-latency OFF response, suggesting that these cells are in actuality OFF-center cells. Overall, the results show that the altered dopaminergic system in degenerate retinas contributes to the deteriorated light responses of RGCs.

Show MeSH
Related in: MedlinePlus