Test of visual pathway function
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1 The visual system
2 Test of visual pathway function Suppose you have a patient who may have some damage to the visual pathways leading to visual cortex, for example from multiple sclerosis. How could you non-invasively investigate where such damage might be? You could use an EEG (electroencephalogram). What kind of visual stimulus should you use to activate as many cells as possible?
3 Test of visual pathway function
4 Test of visual pathway function
5 Test of visual pathway function Reversing checkerboard is a good stimulus for several reasons: The pattern has lots of edges. The pattern changes with time.
6 0.5 mm thick The photosensors (the rods and cones) lie outermost in the retina against the pigment epithelium and choroid. Interneurons Ganglion cells (the output neurons of the retina) lie innermost in the retina closest to the lens and front of the eye. The retina
7 Rods and cones
8 It s important to know how the photoreceptors work, because modern methods are becoming available to compensate for malfunctions in many parts of the phototransduction pathway. Phototransduction Dark Na + Ca ++ Na + Light
9 In the dark, lots of positive charge enters the photoreceptors and leads to transmitter release. Light reduces the charge influx and transmitter release. Phototransduction Dark Na + Ca ++ Na + Light
10 Phototransduction The discs in the outer segment of rods contain rhodopsin molecules in their membranes (up to 100 billion molecules per photoreceptor!). The rods also contain special cation channels (CNG channels) in their outer membranes. (Cyclic nucleotidegated ion channel) High levels of cgmp are present in the dark and keep these channels OPEN. rhodopsin CNG channel (open) cgmp
11 Phototransduction Positive charge enters the rod. This positive charge moves into the inner segment, where it leads to transmitter release. Dark rhodopsin CNG channel (open) cgmp Na + Ca ++ Na
12 How does light shut down transmitter release? Phototransduction rhodopsin CNG channel (open) cgmp +
13 How does light shut down transmitter release? Light activates rhodopsin. Phototransduction rhodopsin CNG channel (open) cgmp * +
14 Phototransduction How does light shut down transmitter release? Light activates rhodopsin. Activated rhodopsin activates a G-protein (transducin). rhodopsin CNG channel (open) cgmp transducin * * +
15 Phototransduction How does light shut down transmitter release? Light activates rhodopsin. Activated rhodopsin activates a G-protein (transducin). Transducin activates cgmp phosphodiesterase (PDE). rhodopsin CNG channel (open) cgmp transducin PDE * * * +
16 Phototransduction How does light shut down transmitter release? Light activates rhodopsin. Activated rhodopsin activates a G-protein (transducin). Transducin activates cgmp phosphodiesterase (PDE). rhodopsin CNG channel (open) cgmp transducin PDE PDE hydrolyzes cgmp. + * * *
17 Phototransduction How does light shut down transmitter release? Light activates rhodopsin. Activated rhodopsin activates a G-protein (transducin). Transducin activates cgmp phosphodiesterase (PDE). PDE hydrolyzes cgmp. The external channels close and less current enters. rhodopsin CNG channel (closed) cgmp transducin PDE * * *
18 More light means that fewer channels are open. The rod HYPERpolarizes! It releases less transmitter as light levels increase. Phototransduction Dark Na + Ca ++ Na + Light
19 Cones work essentially the same way, but they have cone opsins instead of rhodopsin. Phototransduction Dark Na + Ca ++ Na + Light + +
20 Rods vs. cones 110,000,000 to 125,000,000 rods/retina Rods function under dim conditions but not bright conditions 6,400,000 cones/retina Cones will not function in very dimly lit conditions Cones mediate color vision
21 Color vision There are three kinds of cones, with maximum sensitivities to different wavelengths of light. blue: (short wavelength) green: (medium wavelength) red: (long wavelength)
22 The fovea It lies in the center of the macula. The central region contains only cones. The overlying retinal layers are displaced.
23 light
24 Cones are concentrated in the fovea The fovea is especially sensitive to color and detail but functions poorly in badly lit conditions. When you want to look at something, you move your eye so that the image of the object falls on the fovea.
25 The rods are concentrated in the periphery The periphery has high sensitivity under dimly-lit conditions. The periphery has poor resolution of small objects.
26 A family of hereditary diseases of the retina. Caused by at least 25 different mutations in the rod phototransduction cascade. Retinitis Pigmentosa
27 Leads to loss of peripheral vision and can progress to total blindness. A successful gene therapy to replace a faulty rhodopsin gene in one variant was announced in October. Retinitis Pigmentosa
28 Retinal interneurons Photoreceptors synapse onto many postsynaptic interneurons. The interneurons synapse onto one another and onto ganglion cells.
29 Ganglion cells There are about a million ganglion cells. There are at least 18 different types of ganglion cell in the human retina.
30 Ganglion cells Some features of ganglion cells are the same at all regions of the retina but some are very different in the fovea vs. the periphery. Understanding these differences helps to explain the consequences of disorders that affect different parts of the retina. Most of them have properties that convey information about spatial and temporal contrasts Where are there changes in brightness and color? When is the pattern of light changing?
31 Visual field vs. receptive field The term visual field refers to the whole area seen by the eye. The term visual receptive field refers to the part of the visual field where a visual stimulus affects a particular visual system neuron.
32 Ganglion cells Most ganglion cells have center-surround receptive fields. About 50% of those are ON-center OFF-surround. No light Light in center Light in surround
33 ON-center OFF-surround ganglion cells + This ganglion cell responds best (fires fastest) if there is a small spot of light centered in the receptive field.
34 ON-center OFF-surround ganglion cells + This ganglion cell responds best (fires fastest) if there is a small spot of light centered in the receptive field. It responds less to a larger spot of light because a larger spot activates inhibitory inputs to the ganglion cell as well as excitatory. vs
35 Ganglion cells Most ganglion cells have center-surround receptive fields. About 50% of those are ON-center OFF-surround. About 50% of those are OFF-center ON-surround.
36 Ganglion cells The other 50% of the center-surround cells are OFF-center ON-surround. No light Light in center Light only in surround
37 OFF-center ON-surround ganglion cells + These cells respond best to a small dark spot on a bright background. Neither type responds well to an all-bright or alldark field.
38 Sustained vs. transient responses Some respond transiently; some give sustained responses. Some ON-center cells are transient-type; others are sustained. Some OFF-center cells are transient-type; others are sustained. transient cell sustained cell
39 Other types of ganglion cells Some ganglion cells don't have center-surround receptive fields. Some project to superior colliculus and are involved in eye movement control. Some project to the suprachiasmatic nucleus, a region that controls circadian rhythms. Intrinsically photosensitive Contain the photopigment melanopsin (mainly bluesensitive)
40 Receptive field size Ganglion cell centers in the fovea are as small as a fraction of a degree. (The moon is about 0.5.) Ganglion cell centers in the periphery can be up to 5 degrees in diameter.
41 Receptive field size What makes some receptive fields small and others large? Different amounts of convergence determine different receptive field sizes. photoreceptors (thousands) interneurons (bipolars) (hundreds) ganglion cells FOVEA PERIPHERY
42 Receptive field size What is the advantage of having lots of convergence in the rod pathway? Spatial resolution is degraded (objects look fuzzy) but sensitivity to low levels of light is improved. photoreceptors (thousands) interneurons (bipolars) (hundreds) ganglion cells FOVEA PERIPHERY
43 Color vision Red/green centersurround organization is very common. Green ON Red OFF red ON/green OFF red OFF/green ON green ON/red OFF green OFF/red ON
44 Color vision Red/green centersurround organization is very common. Other color-coding cells use blue-yellow contrast. red ON/green OFF red OFF/green ON green ON/red OFF green OFF/red ON
45 Color vision Why is red-green color-blindness so common in males? The opsins for the red and green cones are coded by adjacent regions on the X chromosome and are very similar. They are prone to recombination errors.
46 Foveal vs. peripheral ganglion cells typical cell in fovea sustained color-selective small receptive field some ON-center, some OFF-center typical cell in periphery transient broad-band large receptive field some ON-center, some OFF-center
47
48 Regenerating optic pathways from the eye to the brain Bireswar Laha, Ben K. Stafford and Andrew D. Huberman (June 8, 2017) Science 356 (6342),
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