Rod and cone signaling pathways in mammalian retina

项目总结

PROJECT SUMMARY 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.