Reece Mazade Abstract
Reece Mazade
Ph.D. Candidate (Graduated 08/13/2015)
Physiological Sciences, GIDP
Association for Research in Vision and Ophthalmology
Workshop
Denver, Colorado
May 3-7, 2015
Light adaptation narrows spatial inhibitory input and increases signal output of the mouse inner retina
Authors: Reece E. Mazade1 and Erika D. Eggers2. 1Physiological Sciences GIDP, 2Departments of Physiology and Biomedical Engineering, University of Arizona, Tucson, AZ.
ABSTRACT
Abstract:
Purpose: OFF cone bipolar cells (OFF BCs) in the inner retina bridge the rod and cone pathways by receiving excitatory input from cones and inhibitory input via amacrine cells (ACs) from both rods and cones. We have previously shown that light adaptation of OFF BC inhibition results in a switch from glycinergic to GABAergic inhibition, which changes the source of inhibitory input from morphologically narrow-field glycinergic to wide-field GABAergic ACs. However, it is unknown if this switch changes the spatial inhibitory input to OFF BCs, and as a result the input signal strength to ganglion cells (GC).
Methods: We used whole-cell voltage clamp to record light-evoked inhibitory and excitatory postsynaptic currents from dark-adapted mouse OFF BCs. A white OLED screen was used to set the background light and to generate 25 μm bars of light flashed for 1 sec to map spatial inhibition. The magnitude of light-evoked responses was measured as charge transfer and peak amplitude. The spatial distributions were averaged and compared between light conditions where significance was p<0.05.To evaluate GC input strength, we constructed a model of BC inputs to a GC using simulated BC excitation and inhibition Gaussian distributions to calculate the differences in the spatial strength to GCs under dark and light-adapted conditions.
Results: We predicted that OFF BC spatial inhibition would widen with light adaptation as a result of the wide spatial extent of GABAergic ACs. Surprisingly, we found that the total, isolated GABAergic, and isolated glycinergic spatial inhibition to OFF BCs became narrower with light adaptation (p<0.05). There was no significant change in the spatial input of excitatory responses to the OFF BCs with light adaptation. Our model suggested that when switching from dark to light-adapted conditions, the narrower inner retinal spatial inhibition increases the excitatory strength of distinct spatial inputs to the GCs.
Conclusions: Here we show that light adaptation narrows OFF BC spatial inhibitory input while excitatory spatial input remains unchanged. Adjusting the inhibitory surround of BCs may be part of the mechanism for ganglion cell center-surround changes seen with light adaptation, as a simple model suggests that changes in the inner retina increase ganglion cell excitation to small spots of light. This may be one factor playing a role in increasing visual acuity during the day.
Support: This work was supported by NIH grant EY018131 (EDE), University of Arizona NIH Systems and Integrative Training Grant (REM), the ARCS Foundation (REM), and the Science Foundation Arizona (REM).
Abstract (for Lay Audience)
The retina is the neural layer in the back of the eye that senses light. It can signal a wide range of light intensities, from near darkness under starlight, to bright sunlight during the day. This is accomplished partly through the use of rod photoreceptors that sense dim light, primarily used during night vision, and cone photoreceptors that sense brighter light, used during daytime vision. Photoreceptors send light signals to bipolar cells which send signals to ganglion cells that make up the optic nerve and lead to the brain. This excitatory pathway is modulated by inhibitory amacrine cells. Amacrine cells provide this inhibition and modulate excitatory signals to allow the retina to detect edges and contrast in the surrounding visual scene. Inhibition is vital and necessary for normal vision and sets up our ability to see fine details during the day (high acuity vision/high resolution). The modulation of the photoreceptor signal by light is known but it is not yet well understood how this inhibitory signal is modulated by light.
We have previously found that inhibition may be an important factor for retinal light adaptation, or the ability of the retina to change its signaling when going from a dark to a light environment (night to day). In OFF bipolar cells, which respond to the offset of light sensed by cone photoreceptors, light adaptation changes the type and source of inhibition to these cells. This switch in inhibition underlies a change in type of amacrine cells providing the inhibition, principally a change from small to large amacrine cells. We predicted that a change to large and extensive amacrine cells would cause OFF bipolar cells to be inhibited from light stimuli that were far away from the OFF bipolar cell. Since the amacrine cells utilized in the light-adapted condition are large, they could be activated at long distances away from the OFF bipolar cell that they inhibit. In this way, very small light flashes far away from excitatory pathways would influence them to change the output of the retina.
To investigate this, we recorded inhibitory light responses from mouse OFF bipolar cells in both the dark and the light in response to narrow bars of light which were moved across the retina. This enabled us to map the response to nearby and far away stimuli to see if the transition to larger amacrine cells in the light changed the type of inhibition the OFF bipolar cells received. We then used this data to construct a model of how a change in the inhibition under different light conditions would affect retinal signaling to the ganglion cells, and thus how well the retina can signal fine details in the environment.
Surprisingly, we found that the OFF bipolar cells were not inhibited by far away stimuli in the light, whereas in the dark they were robustly inhibited by both nearby and far away stimuli. Though cell morphology implies that OFF bipolar cells would respond better to far away stimuli in the light, our initial results suggest opposite effects. We also found that the relative levels of inhibition and excitation to these OFF bipolar cells in response to small light stimuli changes between the dark and light. This suggests that factors in addition to the size of amacrine cells may play a role in determining the inhibition that OFF bipolar cells receive. Additionally, our model suggests that these changes in inhibition to small stimuli gives the retina stronger signals in the light. This most likely includes effects of the neuromodulator dopamine, which is released in the light and has been shown to modulate different aspects of retinal light signaling. Adjusting the inhibition to OFF bipolar cells may be part of the mechanism for increasing our ability to see fine details during the day and in bright-light conditions.