This item is under embargo and not available online per the author's request. For access information, please visit http://libanswers.wustl.edu/faq/5640.

Date of Award

Summer 8-15-2016

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Neurosciences)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

The retina is complex neural network that conveys visual information to the brain. It is composed of a wide variety of cell types that establish specific connections to form functional circuits. During development, circuits in the retina generate spontaneous waves of activity that instruct the wiring of the visual system. We study the circuits that produce stage III waves and desynchronize the firing of neighboring ganglion cells with opposite light responses (ON and OFF RGCs), a feature that is thought to help establish parallel ON and OFF pathways in downstream visual areas. We find that intersecting lateral excitatory and vertical inhibitory circuits give rise to precisely patterned stage III retinal waves. The retina can encode a wide range of visual features due to the variety of signals generated by its circuits. Amacrine cells (ACs) are the most diverse class of neurons in the retina yet of the 30 50 AC types in mammalian species, few have been studied in detail. Here, we identify and morphologically characterize three VIP expressing GABAergic AC types (VIP1 , VIP2 and VIP3 ACs) in mice. We find that the somata of VIP1 , VIP2 and VIP3 ACs are asymmetrically distributed along the dorso-ventral axis of the retina and that their neurite arbors differ in size and stratify in distinct sublaminae of the inner plexiform layer. Next, we target VIP ACs under 2 photon guidance for patch clamp recording to analyze light responses and underlying synaptic inputs. We find that VIP1 , VIP2 and VIP3 ACs differ in response polarity and spatial tuning, and contribute to the diversity of inhibitory and neuromodulatory signals in the retina. Finally, to examine the contribution of VIP ACs to visual possessing, we probe how conditional suppression of neurotransmitter release alters circuit function. First, we identify a RGC synaptic pattern using a combination of optogenetics and patch clamp recordings. Then, we chronically silence GABAergic synapses in VIP ACs by genetic deletion of vesicular GABA transporter (VGAT). Preliminary data indicate that this manipulation does not significantly alter downstream light responses. We are currently pursuing additional RGC partners as well as alternative tools to silence VIP ACs.

Language

English (en)

Chair and Committee

Daniel Kerschensteiner

Committee Members

Peter D. Lukasiewicz, Timothy E. Holy, Steven J. Mennerick, Erik D. Herzog

Comments

Permanent URL: http://dx.doi.org/doi:10.7936/K7ST7N79

Available for download on Saturday, August 15, 2116

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