In this competing renewal application, we propose to continue and extend our investigations on rod and cone signaling pathways in the retina by focusing on synaptic circuits responsible for receptive field (RF) organization in retinal ganglion cells (GCs). The goal is to understand the space-time RF properties of different types of mouse GCs in scotopic and photopic conditions, and to identify specific synaptic pathways underlying the adaptation-dependent differences in GC RF profiles. There are two specific aims.
The first aim will study linear space-time RF profiles of various types of GCs in scotopic and photopic conditions, and to determine the degrees of adaptation-dependent differences in each type of GCs, thereby obtaining a comprehensive catalog of mouse GC types by correlating the spike responses to nonlinear whole-field light steps, cell morphology and linear spatiotemporal receptive field (RF) and mosaic profiles.
The second aim will determine contributions of various rod and cone pathways to the spatiotemporal RF profiles of the GCs, and to identify the roles of specific rod and cone pathways in the adaptation-dependent RF differences of individual types of GCs. We will employ the powerful, stable and high throughput multielectrode array (MEA) techniques and the conventional single cell recording methods, in conjunction with the linear white-noise binary checkerboard and the nonlinear whole-field light stimulus protocols to study the spatiotemporal RF profiles of various types of GCs. Our research will provide important mechanistic insights onto the spatiotemporal filtering capacity and RF organization of retinal GCs that can be used to guide future investigations on circuit development and maintenance in healthy retinas, as well as on retinal circuit dysfunctions under various diseased states such as retinitis pigmentosa, congenital stationary night blindness and glaucoma. Knowledge obtained will be useful for developing new gene/drug therapies for retinal disorders and for designing effective retinal prosthetic devices.
The goal of our research is to understand how mammalian retinal ganglion cells process visual information, and how individual retinal neurons and synapses dysfunction in eye diseases, such as retinitis pigmentosa, congenital stationary night blindness and glaucoma. Results obtained will provide a crucial knowledge base for developing new gene/drug therapies against retinal disorders and effective retinal prosthetic devices.
|Lotfi, Parisa; Tse, Dennis Y; Di Ronza, Alberto et al. (2018) Trehalose reduces retinal degeneration, neuroinflammation and storage burden caused by a lysosomal hydrolase deficiency. Autophagy 14:1419-1434|
|Shen, Guofu; Link, Schuyler; Kumar, Sandeep et al. (2018) Characterization of Retinal Ganglion Cell and Optic Nerve Phenotypes Caused by Sustained Intracranial Pressure Elevation in Mice. Sci Rep 8:2856|
|Pang, Ji-Jie; Yang, Zhuo; Jacoby, Roy A et al. (2018) Cone synapses in mammalian retinal rod bipolar cells. J Comp Neurol 526:1896-1909|
|Sabharwal, J; Seilheimer, R L; Tao, X et al. (2017) Elevated IOP alters the space-time profiles in the center and surround of both ON and OFF RGCs in mouse. Proc Natl Acad Sci U S A 114:8859-8864|
|Cowan, Cameron S; Sabharwal, Jasdeep; Seilheimer, Robert L et al. (2017) Distinct subcomponents of mouse retinal ganglion cell receptive fields are differentially altered by light adaptation. Vision Res 131:96-105|
|Palmieri, Michela; Pal, Rituraj; Nelvagal, Hemanth R et al. (2017) mTORC1-independent TFEB activation via Akt inhibition promotes cellular clearance in neurodegenerative storage diseases. Nat Commun 8:14338|
|Tse, Dennis Y; Kim, Seong Jae; Chung, Inyoung et al. (2017) The ocular toxicity and pharmacokinetics of simvastatin following intravitreal injection in mice. Int J Ophthalmol 10:1361-1369|
|Sabharwal, Jasdeep; Seilheimer, Robert L; Cowan, Cameron S et al. (2016) The ON Crossover Circuitry Shapes Spatiotemporal Profile in the Center and Surround of Mouse OFF Retinal Ganglion Cells. Front Neural Circuits 10:106|
|van der Heijden, Meike E; Shah, Priya; Cowan, Cameron S et al. (2016) Effects of Chronic and Acute Intraocular Pressure Elevation on Scotopic and Photopic Contrast Sensitivity in Mice. Invest Ophthalmol Vis Sci 57:3077-87|
|Cowan, Cameron S; Sabharwal, Jasdeep; Wu, Samuel M (2016) Space-time codependence of retinal ganglion cells can be explained by novel and separable components of their receptive fields. Physiol Rep 4:|
Showing the most recent 10 out of 34 publications