Erika D Eggers

Erika D Eggers

Associate Department Head, Research - Physiology
Member of the Graduate Faculty
Professor, BIO5 Institute
Professor, Biomedical Engineering
Professor, Neuroscience - GIDP
Professor, Physiological Sciences - GIDP
Professor, Physiology
Primary Department
Department Affiliations
Contact
(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

Publications

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., O'Brien, J. A., & Berger, A. J. (2000). Developmental changes in the modulation of synaptic glycine receptors by ethanol. Journal of Neurophysiology.
Eggers, E. D., McCall, M. A., & Lukasiewicz, P. D. (2007). Presynaptic inhibition differentially shapes transmission in distinct circuits in the mouse retina. The Journal of physiology, 582(Pt 2), 569-82.

Diverse retinal outputs are mediated by ganglion cells that receive excitatory input from distinct classes of bipolar cells (BCs). These classes of BCs separate visual signals into rod, ON and OFF cone pathways. Although BC signalling is a major determinant of the ganglion cell-mediated retinal output, it is not fully understood how light-evoked, presynaptic inhibition from amacrine cell inputs shapes BC outputs. To determine whether differences in presynaptic inhibition uniquely modulate BC synaptic output to specific ganglion cells, we assessed the inhibitory contributions of GABA(A), GABA(C) and glycine receptors across the BC pathways. Here we show that different proportions of GABA(A) and GABA(C) receptor-mediated inhibition determined the kinetics of GABAergic presynaptic inhibition across different BC classes. Large, slow GABA(C) and small, fast GABA(A) receptor-mediated inputs to rod BCs prolonged light-evoked inhibitory postsynaptic currents (L-IPSCs), while smaller GABA(C) and larger GABA(A) receptor-mediated contributions produced briefer L-IPSCs in ON and OFF cone BCs. Glycinergic inhibition also varied across BC class. In the rod-dominant conditions studied here, slow glycinergic inputs dominated L-IPSCs in OFF cone BCs, attributable to inputs from the rod pathway via AII amacrine cells, while rod and ON cone BCs received little and no glycinergic input, respectively. As these large glycinergic inputs come from rod signalling pathways, in cone-dominant conditions L-IPSCs in OFF cone bipolar cells will probably be dominated by GABA(A) receptor-mediated input. Thus, unique presynaptic receptor combinations mediate distinct forms of inhibition to selectively modulate BC outputs, enhancing the distinctions among parallel retinal signals.

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.