Erika D Eggers
Associate Professor, BIO5 Institute
Associate Professor, Biomedical Engineering
Associate Professor, Neuroscience - GIDP
Associate Professor, Physiological Sciences - GIDP
Associate Professor, Physiology
Primary Department
Department Affiliations
(520) 626-7137
Work Summary
My laboratory studies how the retina takes visual information about the world and transmits it to the brain. We are trying to understand how this signaling responds to changing amounts of background light and becomes dysfunctional in diabetes.
Research Interest
The broad goal of research in our laboratory is to understand how inhibitory inputs influence neuronal signaling and sensory signal processing in the healthy and diabetic retina. Neurons in the brain receive inputs that are both excitatory, increasing neural activity, and inhibitory, decreasing neural activity. Inhibitory and excitatory inputs to neurons must be properly balanced and timed for correct neural signaling to occur. To study sensory inhibition we use the retina, a unique preparation which can be removed intact and can be activated physiologically, with light, in vitro. Thus using the retina as a model system, we can study how inhibitory synaptic physiology influences inhibition in visual processing. This intact system also allows us to determine the mechanisms of retinal damage in early diabetes. Keywords: neuroscience, diabetes, vision, electrophysiology, light


Moore-Dotson, J. M., Beckman, J. J., Mazade, R. E., Hoon, M., Bernstein, A. S., Romero-Aleshire, M. J., Brooks, H. L., & Eggers, E. D. (2016). Early Retinal Neuronal Dysfunction in Diabetic Mice: Reduced Light-Evoked Inhibition Increases Rod Pathway Signaling. Investigative ophthalmology & visual science, 57(3), 1418-30.
BIO5 Collaborators
Heddwen L Brooks, Erika D Eggers

Recent studies suggest that the neural retinal response to light is compromised in diabetes. Electroretinogram studies suggest that the dim light retinal rod pathway is especially susceptible to diabetic damage. The purpose of this study was to determine whether diabetes alters rod pathway signaling.

Eggers, E. D., & Lukasiewicz, P. D. (2006). GABA(A), GABA(C) and glycine receptor-mediated inhibition differentially affects light-evoked signalling from mouse retinal rod bipolar cells. The Journal of physiology, 572(Pt 1), 215-25.

Rod bipolar cells relay visual signals evoked by dim illumination from the outer to the inner retina. GABAergic and glycinergic amacrine cells contact rod bipolar cell terminals, where they modulate transmitter release and contribute to the receptive field properties of third order neurones. However, it is not known how these distinct inhibitory inputs affect rod bipolar cell output and subsequent retinal processing. To determine whether GABA(A), GABA(C) and glycine receptors made different contributions to light-evoked inhibition, we recorded light-evoked inhibitory postsynaptic currents (L-IPSCs) from rod bipolar cells mediated by each pharmacologically isolated receptor. All three receptors contributed to L-IPSCs, but their relative roles differed; GABA(C) receptors transferred significantly more charge than GABA(A) and glycine receptors. We determined how these distinct inhibitory inputs affected rod bipolar cell output by recording light-evoked excitatory postsynaptic currents (L-EPSCs) from postsynaptic AII and A17 amacrine cells. Consistent with their relative contributions to L-IPSCs, GABA(C) receptor activation most effectively reduced the L-EPSCs, while glycine and GABA(A) receptor activation reduced the L-EPSCs to a lesser extent. We also found that GABAergic L-IPSCs in rod bipolar cells were limited by GABA(A) receptor-mediated inhibition between amacrine cells. We show that GABA(A), GABA(C) and glycine receptors mediate functionally distinct inhibition to rod bipolar cells, which differentially modulated light-evoked rod bipolar cell output. Our findings suggest that modulating the relative proportions of these inhibitory inputs could change the characteristics of rod bipolar cell output.

Eggers, E. D., & Moore-Dotson, J. M. (2017). Modulation of retinal calcium signaling in early diabetes. TBD.
Moore-Dotson, J. M., Klein, J. S., Mazade, R. E., & Eggers, E. D. (2015). Different types of retinal inhibition have distinct neurotransmitter release properties. Journal of neurophysiology, jn.00447.2014.

Neurotransmitter release varies between neurons due to differences in presynaptic mechanisms such as Ca(2+)-sensitivity and timing. Retinal rod bipolar cells respond to brief dim illumination with prolonged glutamate release that is tuned by the differential release of GABA and glycine from amacrine cells in the inner retina. To test if differences among types of GABA and glycine release are due to inherent amacrine cell release properties, we directly activated amacrine cell neurotransmitter release by electrical stimulation. We found that the timing of electrically evoked inhibitory currents was inherently slow and that the timecourse of inhibition from slowest to fastest was GABAC receptors ˃ glycine receptors ˃ GABAA receptors. Deconvolution analysis showed that the distinct timing was due to differences in prolonged GABA and glycine release from amacrine cells. The timecourses of slow glycine release and GABA release onto GABAC receptors were reduced by Ca(2+)-buffering with EGTA-AM and BAPTA-AM, but faster GABA release onto GABAA receptors was not, suggesting that release onto GABAA receptors is tightly coupled to Ca(2+). The differential timing of GABA release was detected from spiking amacrine cells and not non-spiking A17 amacrine cells that form a reciprocal synapse with rod bipolar cells. Our results indicate that release from amacrine cells is inherently asynchronous and that the source of non-reciprocal rod bipolar cell inhibition differs between GABA receptors. The slow, differential timecourse of inhibition may be a mechanism to match the prolonged rod bipolar cell glutamate release and provide a way to temporally tune information across retinal pathways.

Eggers, E. D., Mazade, R. E., & Klein, J. S. (2013). Inhibition to retinal rod bipolar cells is regulated by light levels. Journal of neurophysiology, 110(1), 153-61.

The retina responds to a wide range of light stimuli by adaptation of retinal signaling to background light intensity and the use of two different photoreceptors: rods that sense dim light and cones that sense bright light. Rods signal to rod bipolar cells that receive significant inhibition from amacrine cells in the dark, especially from a rod bipolar cell-activated GABAergic amacrine cell. This inhibition modulates the output of rod bipolar cells onto downstream neurons. However, it was not clear how the inhibition of rod bipolar cells changes when rod signaling is limited by an adapting background light and cone signaling becomes dominant. We found that both light-evoked and spontaneous rod bipolar cell inhibition significantly decrease with light adaptation. This suggests a global decrease in the activity of amacrine cells that provide input to rod bipolar cells with light adaptation. However, inhibition to rod bipolar cells is also limited by GABAergic connections between amacrine cells, which decrease GABAergic input to rod bipolar cells. When we removed this serial inhibition, the light-evoked inhibition to rod bipolar cells remained after light adaptation. These results suggest that decreased inhibition to rod bipolar cells after light adaptation is due to decreased rod pathway activity as well as an active increase in inhibition between amacrine cells. Together these serve to limit rod bipolar cell inhibition after light adaptation, when the rod pathway is inactive and modulation of the signal is not required. This suggests an efficiency mechanism in the retina to limit unnecessary signaling.