Limits...
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.

Show MeSH

Related in: MedlinePlus

Effects of dopamine D2-like receptor antagonists on light responses of OFF-center P23H rat RGCs that showed a long-latency ON response.Displayed are spike rasters and PSTHs of spike activity recorded from three RGCs to stimulation with a small (250-μm diameter) spot of light centered over the receptive field. Sulpiride and eticlopride, but not L 745,870, diminished the delayed ON responses (indicated by arrows). Blue horizontal bars indicate the duration of the light stimulus.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4696741&req=5

pone.0146154.g007: Effects of dopamine D2-like receptor antagonists on light responses of OFF-center P23H rat RGCs that showed a long-latency ON response.Displayed are spike rasters and PSTHs of spike activity recorded from three RGCs to stimulation with a small (250-μm diameter) spot of light centered over the receptive field. Sulpiride and eticlopride, but not L 745,870, diminished the delayed ON responses (indicated by arrows). Blue horizontal bars indicate the duration of the light stimulus.

Mentions: An intriguing possibility is that long-latency ON-center RGCs were at one time OFF-center cells early in the disease process. In support of this idea I observed that some OFF-center P23H rat RGCs showed a long-latency ON response when stimulated with a small spot of light. Furthermore, when the cells were exposed to either sulpiride (n = 2 cells) or eticlopride (n = 2 cell), but not L-745,870 (n = 3 cells), the ON responses were selectively reduced (Fig 7). The D2/D3 receptor antagonists sulpiride and eticlopride reduced the long-latency ON responses from 16.5 ± 4.8 to 2.3 ± 1.5 spikes/s (P = 0.004, n = 4). In the presence of the D4 receptor antagonist L-745,870, the long-latency ON responses remained intact (20.3 ± 3.1 spikes/s in control versus 21.7 ± 4.2 spikes/s in the presence of L-745,870, P = 0.742, n = 3). Whether long-latency ON-center RGCs were at one time OFF-center cells early in the disease process will need to be confirmed in future studies.


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 OFF-center P23H rat RGCs that showed a long-latency ON response.Displayed are spike rasters and PSTHs of spike activity recorded from three RGCs to stimulation with a small (250-μm diameter) spot of light centered over the receptive field. Sulpiride and eticlopride, but not L 745,870, diminished the delayed ON responses (indicated by arrows). 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.g007: Effects of dopamine D2-like receptor antagonists on light responses of OFF-center P23H rat RGCs that showed a long-latency ON response.Displayed are spike rasters and PSTHs of spike activity recorded from three RGCs to stimulation with a small (250-μm diameter) spot of light centered over the receptive field. Sulpiride and eticlopride, but not L 745,870, diminished the delayed ON responses (indicated by arrows). Blue horizontal bars indicate the duration of the light stimulus.
Mentions: An intriguing possibility is that long-latency ON-center RGCs were at one time OFF-center cells early in the disease process. In support of this idea I observed that some OFF-center P23H rat RGCs showed a long-latency ON response when stimulated with a small spot of light. Furthermore, when the cells were exposed to either sulpiride (n = 2 cells) or eticlopride (n = 2 cell), but not L-745,870 (n = 3 cells), the ON responses were selectively reduced (Fig 7). The D2/D3 receptor antagonists sulpiride and eticlopride reduced the long-latency ON responses from 16.5 ± 4.8 to 2.3 ± 1.5 spikes/s (P = 0.004, n = 4). In the presence of the D4 receptor antagonist L-745,870, the long-latency ON responses remained intact (20.3 ± 3.1 spikes/s in control versus 21.7 ± 4.2 spikes/s in the presence of L-745,870, P = 0.742, n = 3). Whether long-latency ON-center RGCs were at one time OFF-center cells early in the disease process will need to be confirmed in future studies.

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