1. How the eye sees Last time Anatomy of the eye Cells in the retina Rods and cones Visual receptors This time Visual receptors Visual transduction 1

2. Structure of the eye The Basic Retinal Circuit 1. Receptor Cells (rods and cones) 2. Bipolar Cells 3. Ganglion Cells Different cells in the retina Back of eye Front of eye 4. Horozontal Cells 5. Amacrine Cells 6. Pigment cells 2

3. Photoreceptor cells are the light sensors Back of eye Front of eye 3

4. The visual receptors are G Protein Coupled Receptors seven transmembrane regions hydrophobic/ hydrophilic domains conserved motifs chromophore stably attached to receptor (Schiff’s base Lys296 in TM7) thermostable 4

5. Different opsins recognize different wavelengths We have 4 different opsins Rods: Rhodopsin: blue/green sensitive pigment Cones: S opsin: blue sensitive M opsin: green sensitive L opsin: red sensitive 5

6. The light catcher is 11-cis-retinal covalently attached to opsin GPCR Vitamin A derivative Binds light, changes conformation from 11-cis to all-trans 6

7. Rhodopsins are packed in a crystalline array in the disc Atomic force microscopy 10 rhodopsins/cell 8 7

8. They even make other cells do their work: Pigment cells recycle retinal Interphotoreceptor binding protein Carries retinal to pigment cell Retinal modified to 11-cis Combines with opsin to form rhodopsin Pigment cell Photoreceptor + 8

9. What happens if all rods and cones are killed? 9

10. Unusual retinal gangion cells 10

11. Retinal Ganglion cells express melanopsin, are sensitive to light and project to the superchiasmatic nucleus 11

12. Signal Transduction in Photoreceptor Cells 12

13. Rods respond to single photons of light 13

14. Light hyperpolarizes the cell 14

15. cGMP channels are open in the dark 15

16. The visual cascade is a G protein-coupled cascade Rhodopsin Gtransducin phosophodiesterase cGMP to GMP close cGMP channels 16

17. Signal transduction in the dark 17

18. Signal transduction in the light 18

19. High amplification in the visual cascade Rhodopsin Gtransducin phosophodiesterase cGMP to GMP close cGMP channels 1 100 100 100,000 1000? 19

20. Phototransduction is a highly regulated cascade Adapt to respond over 6 log orders of light 1. Long-term adaptation -pupil size -receptor photobleaching 2. Short-term adaptation -recovery of membrane potential -deactivation of receptors 20

21. Negative regulation of phototransduction Rhodopsin Gtransducin phosophodiesterase cGMP to GMP close cGMP channels Rhod kinase GAP Guanylate cyclase GTP to cGMP open channels Arrrestin Drop in Ca influx activates Ca dissociates from Calmodulin, Opens channels 21

22. Turning off Rhodopsin 22

23. Turning off GPCRs 23

24. Turning off the G protein 24

25. Mice without GAP cannot turn off light response quickly no GAP with GAP (wild-type) 25

26. Phototransduction: Differences between rods and cones Rods Cones Very sensitive to light 30x less sensitive to light each rhodopsin activates 30x less G proteins 26

27. Properties of phototransduction responds to 1 photon of light responds over a range of 6 log orders of light responses are extremely reliable 1000s of discs maximize surface area of light detection high concentration and thermostability of rhodopsin means high detection, low noise adaptation increases the operating range Photoreceptors are highly specialized to detect light! 27