Modulation Of Inner Retinal Inhibition With Light Adaptation

Abstract

The retina is able to adjust its signaling over a wide range of light levels. A functional result of this is increased visual acuity at brighter luminance levels, such as during the day, due to changes in the organization of retinal receptive fields. This process is commonly referred to as light adaptation. These organizational changes have been shown to occur at the level of the ganglion cells, the output neurons of the retina, which have shifts in their excitatory center-inhibitory surround receptive fields that increase their sensitivity to small stimuli. Recent work supports the idea that light-adapted changes in ganglion cell spatial sensitivity are due in part to inner retinal signaling changes, possibly including changes to inhibition onto bipolar cells, the interneurons at the center of retinal signal processing. However, it is unknown how inhibition to the bipolar cells changes with light adaptation, how any changes affect the light signal or what mediates the changes to the bipolar cells that have been suggested by previous reports. To determine how light adaptation affects bipolar cell inhibition, the inhibitory inputs to OFF bipolar cells were measured. OFF bipolar cells, which respond to the offset of light, in particular may be involved in retinal adaptation as they bridge dim- and bright-light retinal pathways. Their inputs were compared between dark- and light-adapted conditions to determine how any inhibitory changes affects their output onto downstream ganglion cells. We found that there was a compensatory switch from primarily glycinergic-mediated inhibition to OFF bipolar cells in the dark to primarily GABAergic-mediated inhibition in the light. Since glycinergic and GABAergic inhibition perform very different roles and are mediated by morphologically different cells, it is likely this switch underlies a change in the spatial distribution of inhibition to these cells. We found that the spatial inhibitory input to OFF bipolar cells became significantly smaller and narrower with light adaptation, translating to smaller inhibitory surrounds of the OFF bipolar cell receptive fields. Through a model, our data suggested that the OFF bipolar cell output to downstream ganglion cells was stronger in the light, due to the narrowing and reduction in the spatial input, to small light stimuli. This would effectively be one way the retina could use to increase visual acuity. Additionally, we found that the inhibitory changes to OFF bipolar cells with light-adaptation are partially mediated by dopamine D1 receptor signaling. Dopamine is released in the light and has been shown to be an important modulator of retinal light-adaptation. However, there are likely other factors involved in mediating inhibitory changes to OFF bipolar cells. Through these studies, we show that light adaptation heavily influences inner retina inhibition and likely plays a prominent role in determining and shaping light signals under different ambient light conditions which may ultimately be one mechanism for increasing visual sensitivity and acuity.