This project addresses a basic research priority of the NEI, how do adaptational changes in retinal networks affect visual processing. The retina responds to light intensities that vary over a billion-fold, but individual retinal neurons can onl vary their output 100-fold. To overcome this disparity between input and output, retinal neurons adapt to background illumination by shifting their response ranges to span ambient illumination intensities. Adaptation occurs within photoreceptors and also at post-receptor locations in the retina. In this proposal we will study two forms of post-receptor adaptation. Using electrophysiological, pharmacological and anatomical approaches, we will investigate the retinal circuits that 1) control the transition from rod to cone signaling and 2) control the variation of center-surround spatial processing at different ambient light levels. A critical feature of the transition from rod- to cone-mediated vision is to suppress rod signaling and enhance cone signaling. Despite extensive study, the circuits responsible for this transition are poorly understood. We discovered a novel form of inhibition that suppresses the function of a critical signaling element, the rod bipolar cell, when it is activated by bright light.
In aim 1, we determie whether this novel form of inhibition in rod bipolar cells contributes to the transition from rod t cone vision. Changes in the level of ambient illumination produce post-receptor adaptation that alters center-surround spatial processing. This form of spatial processing is critical for the detection of edges and spatial contrast. The circuits that mediate this form of post-receptor adaptation are unknown.
In aim 2, we determine the circuits and synaptic mechanisms that produce the adaptational changes in center-surround spatial processing caused by different ambient light levels.

Public Health Relevance

Retinal diseases that cause the loss of photoreceptors and ganglion cells produce changes in information processing that may affect visual perception. These changes in visual processing may be attributable to alterations in the function and wiring of retinal circuitry. By defining retinal circuit function in healthy retinas, our work will lead t a better understanding of visual defects produced by diabetic retinopathy, glaucoma and degenerative photoreceptor diseases.

National Institute of Health (NIH)
Research Project (R01)
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Neurotransporters, Receptors, and Calcium Signaling Study Section (NTRC)
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Greenwell, Thomas
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Washington University
Schools of Medicine
Saint Louis
United States
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Schubert, Timm; Hoon, Mrinalini; Euler, Thomas et al. (2013) Developmental regulation and activity-dependent maintenance of GABAergic presynaptic inhibition onto rod bipolar cell axonal terminals. Neuron 78:124-37
Ichinose, Tomomi; Lukasiewicz, Peter D (2012) The mode of retinal presynaptic inhibition switches with light intensity. J Neurosci 32:4360-71
Eggers, Erika D; Lukasiewicz, Peter D (2011) Multiple pathways of inhibition shape bipolar cell responses in the retina. Vis Neurosci 28:95-108
Sagdullaev, Botir T; Eggers, Erika D; Purgert, Robert et al. (2011) Nonlinear interactions between excitatory and inhibitory retinal synapses control visual output. J Neurosci 31:15102-12
Qiu, Xudong; Goz, Didem (2010) New clues suggest distinct functional roles for M1 and M2 intrinsically photosensitive retinal ganglion cells. J Neurosci 30:1580-1
Eggers, Erika D; Lukasiewicz, Peter D (2010) Interneuron circuits tune inhibition in retinal bipolar cells. J Neurophysiol 103:25-37
Ogilvie, Judith Mosinger; Ohlemiller, Kevin K; Shah, Gul N et al. (2007) Carbonic anhydrase XIV deficiency produces a functional defect in the retinal light response. Proc Natl Acad Sci U S A 104:8514-9
Eggers, Erika D; McCall, Maureen A; Lukasiewicz, Peter D (2007) Presynaptic inhibition differentially shapes transmission in distinct circuits in the mouse retina. J Physiol 582:569-82
Ichinose, Tomomi; Lukasiewicz, Peter D (2007) Ambient light regulates sodium channel activity to dynamically control retinal signaling. J Neurosci 27:4756-64
Sagdullaev, Botir T; McCall, Maureen A; Lukasiewicz, Peter D (2006) Presynaptic inhibition modulates spillover, creating distinct dynamic response ranges of sensory output. Neuron 50:923-35

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