1How the eye seesLast timeAnatomy of the eyeRods and conesVisual receptorsColor VisionThis timeVisual transductionEye to brain1Rods and cones have different visual receptorsThe visual receptors are G protein-coupled receptors• seven transmembraneregions• hydrophobic/ hydrophilic domains• conserved motifs• chromophore stably attached to receptor(Schiff’s base Lys296 in TM7)• thermostable2Nomenclature for visual receptorsReceptor == GPCR, opsinLigand == chromophore, retinal, pigmentReceptor bound to ligand == rhodopsinLight hyperpolarizes the cell32The visual cascade is a G protein-coupled cascadeRhodopsin Gtransducin phosophodiesterase cGMP to GMP close cGMP channels4Signal transduction in the dark5Signal transduction in the light63Negative regulation of phototransductionRhodopsin Gtransducin phosophodiesterase cGMP to GMP close cGMP channels7Closing cGMP channels causes a decrease in Ca2+Decrease in Ca2+ activates1. Rhodopsin kinase === deactivate receptor2. Guanylate cyclase === converts GTP to cGMP === opens cGMP channelsCa2+ independent deactivation also occurs1. GTPase activating proteinTurning off rhodopsin8Ca-dependentTurning ON Guanylate CyclaseGuanylate cyclase GTP--- cGMP opens cGMP channels GCAP (less Ca) Phosphodiesterase cGMP--- GMP closes cGMPchannels transducinENZYME REACTION ACTION on CHANNELS ACTIVATED BYCa-dependent,Decrease in Caactivates GC94Turning off the G protein10Mice without GAP cannot turn off light response quicklyno GAPwith GAP (wild-type)11Rods respond to a single photon of light125Single photon response is very reproducible13Dark noise is very low1 rhodopsin/minute108rhodopins/ photoreceptor1000 years for all rhodopsins to turn over14High amplification increases signal size and reliabilityRhodopsin Gtransducin phosophodiesterase cGMP to GMP close cGMP channels1 100 100 100,000 ~1000156Properties of phototransduction• responds to 1 photon of light• responses are extremely reliable• high amplification of signaling• low dark noise•1000s of discs maximize surface area of light detection• high concentration and thermostability of rhodopsin means high detection, low noisePhotoreceptors are highly specialized to detect light!16Phototransduction: Differences between rods and conesRods ConesVery sensitive to light 30x less sensitive to lighteach rhodopsin activates 30x less G proteins17Drosophila mutants with abnormal light responses187The signaling pathway for Drosophila phototransductionFastest GPCR cascade measuredNo amplification19Structure of the eyeThe Basic Retinal Circuit1. Receptor Cells(rods and cones)2. Bipolar Cells3. Ganglion CellsConnectivity in the retinaBack of eyeFront of eye4. Horozontal Cells5. Amacrine Cells6. Pigment cells20View of the retinaRamon y Cajal, Nobel 1906218Flow of visual information in the retinaVertical ConnectionsBack of eye Front of eye back of eyePhotoreceptor Cell---Bipolar Cell---Retinal Ganglion Cell---BrainHorozontal ConnectionsHorozontal Cells- connect photoreceptors and bipolar cellsAmacrine Cells- connect bipolar cells and retinal ganglion cellslight22What happens if all rods and cones are killed?23Unusual retinal gangion cells249Retinal ganglion cells express melanopsin, are sensitive to lightand project to the suprachiasmatic