Abstract
Purpose: Dark adapted mouse retinal ganglion cells (RGCs) can be distinguished based on their extensive range of thresholds covering 3 log units. We previously showed that blockade of GABA circuits shifted the thresholds of RGCs suggesting that inhibition controls their sensitivity. Here we compared the effects of GABAergic, glycinergic, and dopaminergic drugs on the threshold sensitivity and excitability of RGCs.
Methods: We recorded the spike activity of mouse RGCs with a MEA. The intensity-response (I-R) functions were computed under control and drug conditions. The threshold sensitivity of single cells was computed as 5% of the maximum response spike frequency. Overall excitability was calculated from the average spike frequency to threshold, half-maximal, and maximal responses to light.
Results: Application of the GABA receptor blocker PTX (100 μM) produced an increased threshold sensitivity of most RGCs of between 1-3 log units (n=33). Measurements of excitability showed an average 2.7 ± 0.1 fold increase in spiking. However, while high sensitivity (HS) cells also showed a 2.7 ± 0.2 fold increase in spike frequency following PTX application, they did not show an increase in threshold sensitivity (0.03 ± 0.03 log unit change, n=10). Application of the glycine blocker strychnine produced a very small increase in RGC threshold sensitivity (0.07 ± 0.07 log units, n=42). However, these cells showed a large increase in excitability evidenced by a 3.6 ± 1.0 fold increase in light-evoked spiking with strychnine. Application of the D1 receptor blocker SCH-23390 (10 μM) produced a 0.66 ± 0.37 log unit (n=51) reduction in the threshold sensitivity, whereas application of the D2 receptor blocker eticlopride (25 μM) decreased the threshold sensitivity of RGCs by 0.30 ± 0.33 (n=97) log units. However, neither DI nor D2 receptor blockade produced a change in cell excitability (1.0 ± 0.1 fold change).
Conclusions: Our results indicate that GABAergic inhibition has the most profound effects on threshold sensitivities of mouse RGCs. Dopaminergic pathways also control RGC threshold sensitivity, but to a smaller degree. Glycinergic circuits clearly affected overall RGC excitability, but had little effect on threshold sensitivity. The disassociation of the changes in threshold sensitivity and excitability of single RGCs suggests that these properties arise from and are controlled by different mechanisms.
Methods: We recorded the spike activity of mouse RGCs with a MEA. The intensity-response (I-R) functions were computed under control and drug conditions. The threshold sensitivity of single cells was computed as 5% of the maximum response spike frequency. Overall excitability was calculated from the average spike frequency to threshold, half-maximal, and maximal responses to light.
Results: Application of the GABA receptor blocker PTX (100 μM) produced an increased threshold sensitivity of most RGCs of between 1-3 log units (n=33). Measurements of excitability showed an average 2.7 ± 0.1 fold increase in spiking. However, while high sensitivity (HS) cells also showed a 2.7 ± 0.2 fold increase in spike frequency following PTX application, they did not show an increase in threshold sensitivity (0.03 ± 0.03 log unit change, n=10). Application of the glycine blocker strychnine produced a very small increase in RGC threshold sensitivity (0.07 ± 0.07 log units, n=42). However, these cells showed a large increase in excitability evidenced by a 3.6 ± 1.0 fold increase in light-evoked spiking with strychnine. Application of the D1 receptor blocker SCH-23390 (10 μM) produced a 0.66 ± 0.37 log unit (n=51) reduction in the threshold sensitivity, whereas application of the D2 receptor blocker eticlopride (25 μM) decreased the threshold sensitivity of RGCs by 0.30 ± 0.33 (n=97) log units. However, neither DI nor D2 receptor blockade produced a change in cell excitability (1.0 ± 0.1 fold change).
Conclusions: Our results indicate that GABAergic inhibition has the most profound effects on threshold sensitivities of mouse RGCs. Dopaminergic pathways also control RGC threshold sensitivity, but to a smaller degree. Glycinergic circuits clearly affected overall RGC excitability, but had little effect on threshold sensitivity. The disassociation of the changes in threshold sensitivity and excitability of single RGCs suggests that these properties arise from and are controlled by different mechanisms.
| Original language | English |
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| Title of host publication | Investigative Ophthalmology & Visual Science |
| ISBN (Electronic) | 1552-5783 |
| Publication status | Published - 2015 |
| Externally published | Yes |
| Event | The Association for Research in Vision and Ophthalmology Annual Meeting - , United States Duration: 3 May 2015 → 7 May 2015 |
Conference
| Conference | The Association for Research in Vision and Ophthalmology Annual Meeting |
|---|---|
| Country/Territory | United States |
| Period | 3/05/15 → 7/05/15 |