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Advisory Committee Chair

Kent T Keyser

Advisory Committee Members

Franklin R Amthor

Paul D Gamlin

Lori L McMahon

Eugenie Hartmann

Document Type

Dissertation

Date of Award

2012

Degree Name by School

Doctor of Philosophy (PhD) School of Optometry

Abstract

Acetylcholine (ACh) is the first identified neurotransmitter and acts in areas including the peripheral nervous system (PNS) and the central nervous system (CNS). The effects of ACh are mediated by nicotinic and muscarinic acetylcholine receptors (AChRs), both of which are extensively distributed in CNS, including the retina. The expression and distribution of nicotinic AChRs (nAChRs) and muscarinic AChRs (mAChRs) have been studied with RT-PCR, western blot, and immunohistochemical techniques in the retinas of different species (Kaneda et al., 1995; Keyser et al., 2000; Yamada et al., 2003; Strang et al., 2005; Dmitrieva et al., 2007; Liu et al., 2009; Strang et al., 2010). However, the roles of nicotinic and muscarinic AChRs in retinal information processing are still not fully understood. The studies which comprise this dissertation describe the expression pattern of nicotinic and muscarinic AChRs in relation to each other and demonstrate that nicotinic and muscarinic activation differentially affect ganglion cell light evoked responses, and thus visual processing in the retina. Immunohistochemisty results show that m1 and m4 mAChRs were expressed together with non-α7 and α7 nAChRs and that there was no apparent overlap in the expression patterns of m2 or m3 and nAChRs. Electrophysiological recordings revealed that blockade of nAChR and mAChRs resulted in either increases or decreases in ganglion cell light responses and the cholinergic effects were ganglion cell-type specific. The data suggest that retinal ganglion cells have unique response properties shaped by the pattern of AChR expression. The effects of mAChR activation on center-surround receptive field organization in concentric ganglion cells were studied by electrophysiological recordings. Specific ganglion cell types were identified by physiological and morphological criteria. Agonist and antagonists of mAChRs were applied to evaluate the alteration of receptive field organization by activation and blockade of specific mAChR subtypes. The activation of excitatory and inhibitory mAChR subtypes expressed in vertical and lateral pathways appear to be essential for the center-surround organization characteristics of concentric ganglion cells. These data help to explain the mechanisms of endogenous cholinergic signaling and the contributions of mAChR activation to spatial frequency properties in visual processing.

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Optometry Commons

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