Selective Modulation of Retinal Ganglion Cell Responses by Nitric Oxide

Core Concepts

Nitric oxide selectively modulates the temporal response properties of a distinct subset of contrast-suppressed retinal ganglion cell types, reducing their response suppression and increasing their activity, without affecting their spatial receptive field properties.

Abstract

The study investigated the neuromodulatory effects of nitric oxide (NO) on the responses of retinal ganglion cells (RGCs) in the mouse retina. Using two-photon calcium imaging and multi-electrode array recordings, the authors found that: Certain RGC types displayed highly reproducible, cell type-specific adaptational response changes over the course of the experiment, even in the absence of pharmacological manipulation. This highlights the importance of using a paired recording paradigm to disentangle adaptational from drug-induced effects. Elevating NO levels selectively modulated the temporal response properties of a distinct subset of contrast-suppressed RGC types (G32 and its subtypes). NO reduced the response suppression and increased the activity of these RGCs, without affecting their spatial receptive field properties. The authors identified three functionally distinct subtypes within the G32 RGC group, all of which were differentially modulated by NO. The NO-induced effects were reversible and included faster response kinetics, as confirmed by the higher temporal resolution multi-electrode array recordings. The majority of other RGC types showed either stable responses or adaptational changes unrelated to NO. This highlights the highly selective nature of NO's neuromodulatory effects on the retinal output. Overall, the results suggest that NO signals information about fast-changing contrasts in the visual environment by selectively modulating the temporal response properties of a specific subset of RGCs, which may relay this information to higher visual processing regions.

Stats

"Surprisingly, while the majority of RGC types featured stable responses (e.g., G1, G21; Fig. 3a), a substantial number of RGC types (∼34%) changed their responses to chirp and/or moving bar stimuli in the absence of any pharmacological perturbation in a highly reproducible manner (Fig. 3b)." "We found that the distributions of the predicted RGC types in our datasets matched that of the earlier dataset quite well (Fig. 2b-d)." "Strychnine application revealed additional On-responses in Off (e.g., G1, G2) and On-Off RGCs (e.g., G12), as can be seen, for instance, in their leading-edge response to the moving bar (Fig. S2; left panel, middle column)." "We found that the percentage of changing types per functional group was similar to that in the control dataset: 'Off' (0% (0/5)), 'On-Off' (50% (2/4)), 'Fast On' (34% (1/3)), 'Slow On' (66% (4/6)), and 'Uncertain RGCs' (66% (2/3))." "We found that the adaptational and NO-induced effects occurred on a feature-specific as well as cell type-specific level."

Quotes

"Surprisingly, while the majority of RGC types featured stable responses (e.g., G1, G21; Fig. 3a), a substantial number of RGC types (∼34%) changed their responses to chirp and/or moving bar stimuli in the absence of any pharmacological perturbation in a highly reproducible manner (Fig. 3b)." "Remarkably, we found that about one-third of the RGC types, recorded using two-photon Ca2+ imaging, exhibited consistent, cell type-specific adaptational response changes throughout an experiment, independent of NO." "Taken together, our research highlights the selective neuromodulatory effects of NO on RGCs and emphasizes the need of considering non-pharmacological activity changes, like adaptation, in such study designs."

Key Insights Distilled From

Nitric oxide modulates contrast suppression in a subset of mouse retinal ganglion cells

by Gonschorek,D... at www.biorxiv.org 12-23-2023

https://www.biorxiv.org/content/10.1101/2023.12.23.572742v2

Deeper Inquiries

How do the adaptational and NO-induced response changes in RGCs relate to their functional roles in visual processing and information transmission to higher brain regions

The adaptational and NO-induced response changes in retinal ganglion cells (RGCs) play a crucial role in their functional roles in visual processing and information transmission to higher brain regions. Adaptational changes, observed in about one-third of RGC types, likely reflect the dynamic nature of the retina's response to changing environmental conditions. These changes may help optimize visual processing by adjusting the sensitivity and responsiveness of different RGC types to varying stimuli. On the other hand, NO-induced response changes, particularly in contrast-suppressed RGC types, suggest a specific modulation of these cells' activity by nitric oxide. This modulation could enhance the transmission of fast contrast changes to higher visual regions, contributing to the refinement of visual information processing and signaling in the retina.

What are the potential mechanisms underlying the cell type-specific adaptational changes observed in the absence of pharmacological manipulation

The cell type-specific adaptational changes observed in the absence of pharmacological manipulation may be driven by various mechanisms related to the ex vivo condition of the retina and the experimental setup. These changes could be influenced by factors such as the depletion of extracellular signaling molecules, washout of neuromodulators, or adjustments in the retinal circuitry to the experimental environment. Additionally, factors like light adaptation, temperature, and perfusion medium composition may contribute to the differential adaptation of various RGC types. The adaptational changes likely reflect the retina's ability to dynamically adjust its responses to maintain optimal visual processing under changing conditions.

Could the selective modulation of contrast-suppressed RGC types by NO be related to its proposed role in signaling fast changes in light levels and visual contrast under photopic conditions

The selective modulation of contrast-suppressed RGC types by nitric oxide (NO) could be closely related to its proposed role in signaling fast changes in light levels and visual contrast under photopic conditions. NO has been implicated in regulating the transition between scotopic and photopic signaling pathways, suggesting its involvement in adapting the retina to different light levels. By selectively modulating the activity of contrast-suppressed RGC types, NO may enhance the transmission of rapid changes in visual contrast to higher brain regions, allowing for more precise and efficient processing of visual information. This selective modulation by NO highlights its role in fine-tuning specific aspects of visual processing in the retina, particularly in response to dynamic changes in the visual environment.