June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Partial cone loss triggers differential recruitment of inhibitory circuits to two retinal OFF ganglion cell channels.
Author Affiliations & Notes
  • Joo Yeun Lee
    University of California San Francisco, San Francisco, California, United States
  • Felice Dunn
    University of California San Francisco, San Francisco, California, United States
  • Footnotes
    Commercial Relationships   Joo Yeun Lee None; Felice Dunn None
  • Footnotes
    Support  K99 Grant EY033858
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 5245. doi:
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      Joo Yeun Lee, Felice Dunn; Partial cone loss triggers differential recruitment of inhibitory circuits to two retinal OFF ganglion cell channels.. Invest. Ophthalmol. Vis. Sci. 2023;64(8):5245.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Previously, we found that partial cone loss triggers inhibition in ON pathways to increase spatiotemporal integration in the mature retina. However, it is unclear how functionally distinct microcircuits, e.g., ON vs. OFF pathways or specific ganglion cell (RGC) types, are affected by partial cone loss. We ask (1) whether two OFF RGCs, alpha OFF-sustained (AOFF-S) and OFF-transient (AOFF-T) cells, exhibit common or unique reactions to partial cone loss, and (2) which inhibitory circuits, i.e., glycinergic or GABAergic inhibition, compensate for fewer cones.

Methods : We achieved acute partial cone ablation in the mature mouse retina by expressing the simian diphtheria toxin receptor under a promoter for the M-opsin gene and injecting diphtheria toxin after postnatal day 30. We compared the changes in spatiotemporal processing in OFF pathways by making whole-cell patch-clamp recordings from AOFF-S and AOFF-T RGCs in response to the following bar noise stimuli: (1) light intensity of each bar fluctuated randomly across time vs. (2) alternating bars that were held constant at the background intensity to mimic unresponsive cones while the other half fluctuated in intensity. Finally, we recorded from alpha-OFF RGCs in the presence of strychnine or picrotoxin to probe how inhibitory pathways contribute to spatiotemporal modifications following partial cone loss.

Results : Our data indicate the expansion of spatial surround filters for cone-mediated receptive fields of both AOFF-S and AOFF-T RGCs, but the degree of spatial changes were greater in AOFF-T RGCs. In addition, AOFF-T RGCs exhibited greater changes in kinetics following cone loss, i,e., slower speeds, greater integration, and weaker differentiation compared to AOFF-S RGCs. Such different responses between two cell types suggest that spatiotemporal modifications occur after divergence between the OFF pathways. Lastly, pharmacology experiments revealed a mechanism by which spatiotemporal changes are mediated by serial connections among amacrine cells onto OFF pathways.

Conclusions : Our results demonstrate differential adjustments of functional responses between OFF channels indicating that partial cone loss triggers recruitment of inhibitory circuits after divergence of these two OFF channels. Further, we reveal the addition of serial GABA-to-glycine inhibition onto OFF pathways that underlies the spatiotemporal adjustments.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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