Date on Master's Thesis/Doctoral Dissertation

5-2019

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Anatomical Sciences and Neurobiology

Degree Program

Anatomical Sciences and Neurobiology, PhD

Committee Chair

McCall, Maureen

Committee Co-Chair (if applicable)

Borghuis, Bart

Committee Member

Borghuis, Bart

Committee Member

Gregg, Ron

Committee Member

Guido, William

Committee Member

Petruska, Jeffrey

Author's Keywords

rAAV; shRNA; glycine receptor kinetics; inhibitory retinal circuits; GlyRα1, GlyRα2, GlyRα3, GlyRα4; starburst amacrine cell

Abstract

Retinal ganglion cells (RGCs) represent the culmination of all retinal signaling and their output forms the substrate for vision throughout the rest of the brain. About 40 different RGC types have been defined by differences in their visually evoked responses, morphology, and genetic makeup. These responses arise from interactions between inhibition and excitation throughout the retinal circuit (Franke et al., 2017; Masland, 2012; Sanes & Masland, 2015; Werblin, 2011). Unlike most other areas of the central nervous system (CNS), the retina utilizes both GABA and glycine inhibitory neurotransmitters to refine glutamatergic excitatory signals (Franke & Baden, 2017; Werblin, 2011; C. Zhang, Nobles, & McCall, 2015). Glycine receptors (GlyRs) are heteromers composed of a single β subunit and one of four α subunits, with a stoichiometry of 3β:2α (Grudzinska et al., 2005; Heinze, Harvey, Haverkamp, & Wassle, 2007; Lynch, 2004). All four GlyRα subunits (α1, α2, α3, or α4) are differentially expressed in the retina and subunit specific expression has been defined for bipolar, some amacrine cells and vi RGCs (Haverkamp, Muller, Zeilhofer, Harvey, & Wassle, 2004; Heinze et al., 2007). The roles for GlyRα subunit specific inhibition are unknown, although glycinergic input is generally linked to temporal response tuning (Murphy & Rieke, 2006; Nobles, Zhang, Muller, Betz, & McCall, 2012; van Wyk, Wassle, & Taylor, 2009; Wassle et al., 2009; Werblin, 2010). We have surveyed GlyRα subunit expression in a variety of identified RGC types, using GlyRα knockout mice and an rAAV-mediated RNAi to knockdown GlyRα subunit specific expression. We find that the four α RGCs only express GlyRα1. All of the other RGCs we studied express at least two GlyRα subunits. In some RGCs, the GlyR kinetics are similar, whereas in others the kinetics differs. We propose that this diversity will contribute to the richness of retinal inhibitory processing.

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