Transient receptor potential cation channel, subfamilies V, member 1 (TRPV1) and M, member 1 (TRPM1) contribute to neural signaling in mouse retina.

Abstract

Transient receptor potential cation channel, subfamilies V, member 1 (TRPV1) and M, member 1 (TRPM1) contribute to neural signaling in mouse retina. Jennifer Noel University of LouisvilleFollow this and additional works at: https://ir.library.louisville.edu/etd Part of the Biology Commons, and the Molecular and Cellular Neuroscience CommonsThis Doctoral Dissertation is brought to you for free and open access by ThinkIR: The University of Louisville's Institutional Repository. It has been accepted for inclusion in Electronic Theses and Dissertations by an authorized administrator of ThinkIR: The University of Louisville's Institutional Repository. This title appears here courtesy of the author, who has retained all other copyrights. For more information, please contact thinkir@louisville.edu. Recommended CitationNoel, Jennifer, "Transient receptor potential cation channel, subfamilies V, member 1 (TRPV1) and M, member 1 (TRPM1) contribute to neural signaling in mouse retina." (2016) Trp channels modulate the responses of retinal neurons within specific pathways..The study of the expression and function of the majority of Trp channels in the retina is largely in its infancy. My dissertation first investigated the expression and function of the transient receptor potential vanilloid-1 (TRPV1) receptor/channel in the retina. TRPV1, the first cloned and most highly studiedTrp channel in the peripheral nervous system, is a non-selective cation channel with an affinity for Ca 2+ . The channel can be activated by capsaicin, acid, endovanilloids, noxious heat or pressure (Moreira et al., 2012). Located on the peripheral and central terminals of nociceptive fibers in the PNS and in limited areas of the CNS (Cavanaugh et al, 2011b). TRPV1 plays a role in inflammation, chronic pain, nociceptor sensitization and desensitization, long-term depression vi and potentiation, and apoptosis. The role of TRPV1 in the retina is not known.Using the electroretinogram (ERG), a mass potential that assesses the function of photoreceptors and bipolar cells, the TRPV1 knockout mouse appears normal.However, TRPV1 is thought to play a role in calcium regulation and glaucoma (Sappington et al., 2009& Leonelli et al., 2010 so we investigated its role in normal visual transduction in the inner retina. To investigate TRPV1 modulation, Irecorded GC spiking responses to light stimuli from mice which either express or lack TRPV1 protein. I found that TRPV1 is critical for:1. GC responses to dim light. Sustained responses to light3. Surround suppression of GCs to large spots. (LRIT3), a novel protein component in the mGluR6-TRPM1 signalplex that was found mutated within cCSNB patients and a knockout mouse (Zeitz et al., 2013; Neuillé et al., 2014). The function of LRIT3 within the cascade remains unknown.To better understand the role of LRIT3, we examined retinal structure and function. We compared the structure of the pre and postsynaptic elements in the OPL of WT and Lrit3 -/-mice using a variety of antibodies and with confocal microscopy. We as...