Functional characteristics of rod pathways in the retina

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DESCRIPTION (provided by applicant): This proposal is aimed at understanding the properties of the rod circuitry in the mammalian retina. Our rod vision encompasses lights as dim as a single photon absorption in as many as 10,000 rod photoreceptors, up to 1000 or more photons per rod. This wide range of light sensitivity is accomplished by biophysical mechanisms that have been studied for more than a half century, but several outstanding issues of fundamental importance remain. The experiments described in this proposal are designed to address two issues: (1) Which aspects of the rod photoresponse are relevant for downstream processing?, and (2) What are the threshold and dynamic range of light intensities for each retinal pathway that relays the rod photoresponse to ganglion cells? To answer these questions we will record light-evoked responses from rod photoreceptors, bipolar cells and ganglion cells from several transgenic mouse lines lacking cone light responses (cone trasducin -/-) with: (1) knockouts in the rod phototransduction pathway that change the shape of the rod photoresponse, and (2) knockouts in the retinal circuitry that will allow the rod retinal pathways (Rod-Bipolar, Rod-Cone, and Rod-Off pathways) to be studied in isolation. The deletion of the phototransduction proteins (GCAP, Rhodopsin Kinase, Rhodopsin, and Arrestin), or the gap junction protein Connexin 36 in specific cells, will alter the transmission of light responses and allow us to infer how the properties of the photoresponse and circuitry influence rod vision. In parallel with these experiments, we will evaluate the behavioral threshold for rod vision in each mouse studied. Thus alterations in the physiology of rod signaling in the retina can be connected to a constrained and quantifiable visual behavior. Such correlations will provide insights into how the processing of the rod photoresponse influences perception, and will have consequences for understanding the mechanistic basis for deficits in rod vision (i.e. Stationary Night Blindness). Night vision in mammals is mediated by several pathways in the retina that relay information about few photon absorptions to the brain. This proposal is aimed at understanding how this remarkable sensitivity is achieved at the cellular level by establishing the properties of the rod photoreceptor response and the retinal circuitry that are important for visual processing. In order to devise therapies for conditions that influence our night vision, like Stationary Night Blindness, it is necessary to first understand the physiological mechanisms that relay information from our eyes to our brain at low light levels.