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Vision
- A glance at an object lets us know where it is, its size, shape, color, texture, direction and speed of movement.
- We can do this at many different intensities of light from faint light to bright sunlight.
- Two main components of the CNS are responsible for this: the retina in the eye and the visual centers of the brain.
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Today’s learning goals
- Be able to identify the different parts of the eye and their functions.
- Understand the main proteins involved in the signal transduction pathway that leads to changes in neurotransmitter release by photoreceptors in response to light.
- Learn the neural pathway that takes information from photoreceptors to the brain.
- Understand the concept of the receptive field.
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The human eye
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Anatomy of the Human Eye
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Title Text
http://courses.pbsci.ucsc.edu/mcdb/bio125/Animation11-01AnatomyoftheHumanEye.mov
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Parts of the eye
- Outside:
- Sclera– outer layer composed of white fibrous tissue.
- Cornea– front part of eye, transparent, provides 80% focusing power of the eye
- Middle:
- Iris– colored portion of the eye, contains muscles that adjust the pupil size under neural control. Open during dim light, closed during bright light.
- Ciliary body– ring of tissue that encircles the lens and includes both a muscle component and a vascular component.
- Choroid– composed of a rich capillary bed that serves as the main blood supply for the photoreceptors and contains melanin containing cells.
- Inside:
- Retina– neural part of the eye, detects light, processes information, and sends it to the brain.
- Lens– transparent structure that and change shape to allow fine focus.
- Aqueous humor– in anterior chamber, supplies nutrients to anterior eye.
- Vitreous humor– gelatinous substance in posterior chamber, provides shape, contains macrophages that removes debris.
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Anterior of the human eye in the unaccommodated and accommodated state
Accommodation to focusing on near objects involves the contraction
of the ciliary muscle, which reduces tension of the Zonule fibers
and the lens is allowed to increase its curvature
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Increased curvature in an optical lens increases the refraction of light, allowing closer focal distance.
Contraction of ciliary muscle
Myopia & Hyperopia
- Myopia: eyeball too long or cornea too curved while lens is as flat as can be. Image focuses in front. Near sightedness
- Hyperopia: eyeball too short or refracting system too weak. Image focuses behind eye. Far sightedness
Getting old sucks…need reading glasses
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Getting old lens loses elasticity with age.
diopter (us), is a unit of measurement of the optical power of a lens or curved mirror, which is equal to the reciprocal of the focal length measured in metres (that is, 1/metres)
Diseases of the anterior eye
- Cataracts– clouding of the lens
- Floaters– happens when the vitreous slowly shrinks, it becomes stringy and the strands cast a shadow on the retina.
- Refractive errors, near and far sightedness.
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Lens proteins denature and degrade over time, and this process is accelerated by diseases.
genetic disorder, diabetes, surgery, long term steroid use, UV light
from: https://en.wikipedia.org/wiki/Lens_(anatomy)
Crystallins are water-soluble proteins that compose over 90% of the protein within the lens
The three main crystallin types found in the human eye are α-, β-, and γ-crystallins.
The refractive index of human lens varies from approximately 1.406 in the central layers down to 1.386 in less dense layers of the lens.[10] This index gradient enhances the optical power of the lens
Crystallins tend to form soluble, high-molecular weight aggregates that pack tightly in lens fibers
lens capsule is a smooth, transparent basement membrane that completely surrounds the lens. The capsule is elastic and is composed of collagen. It is synthesized by the lens epithelium and its main components are Type IV collagen and sulfated glycosaminoglycans (GAGs)
cells of the lens epithelium also serve as the progenitors for new lens fibers. It constantly lays down fibers in the embryo, fetus, infant, and adult, and continues to lay down fibers for lifelong growth
lens fibers form the bulk of the lens. They are long, thin, transparent cells, firmly packed, with diameters typically 4–7 micrometres and lengths of up to 12 mm long
In many aquatic vertebrates, the lens is considerably thicker, almost spherical, to increase the refraction
among terrestrial animals, however, the lens of primates such as humans is unusually flat
The retina
- The retina, despite its peripheral location, is part of the CNS.
- Contains neural circuitry that converts light energy into action potentials that travel out of the eye within the optic nerve into the brain.
- Is a layered structure, relatively simple for a CNS structure.
- Surrounded on one side by pigmented epithelium which contains melanin that helps reduce backscattering of light. Also plays a role in maintenance of photoreceptors.
- 5 types of neurons in the retina: photoreceptors, bipolar cells, retinal ganglion cells, horizontal cells, and amacrine cells.
- A direct 3 neuron chain is the basic unit of transmission. Photoreceptor to bipolar cell to ganglion cell.
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neural crest—> PNS
neural tube—> CNS (and retina)
Anatomy of the retina
- Light travels through the retina to hit the photoreceptors in the photoreceptor layer
Neuroscience 5e Fig. 11.5
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from: http://www.huffingtonpost.com/2015/03/18/human-retina-backwards_n_6885858.html
researchers at Technion–Israel Institute of Technology in Haifa built a computer model of a human retina and then compared how light behaves in the model with the way it behaves in the retinas of guinea pigs.
The comparison showed that when light travels through cell layers before reaching the rods and cones (photoreceptors), it's actually being sorted into red, green, and blue light
What's doing the sorting? Tiny structures known as Muller glia cells, according to the researchers.
However >"We should also remember that several animal classes do not have a 'backward-pointing' eye, and also have Muller cells,"
study was presented at a meeting of the American Physical Society on March 5, 2015 in San Antonio, Texas.
from: http://hubel.med.harvard.edu/book/b8.htm
Because the rods and cones are at the back of the retina, the incoming light has to go through the other two layers in order to stimulate them. We do not fully understand why the retina develops in this curious backward fashion.
One possible reason is the location behind the receptors of a row of cells containing a black pigment, melanin (also found in skin)
number of rods and cones vary across the retina. In the center where vision is best (fovea) there are only cones. This area is about 0.5mm in diameter.
125 million rods and cones in each eye. But only 1 million ganglion cells. How is visual information then preserved. Think of two paths: the direct path and an indirect path involving lateral interactions mediated by horizontal cells between receptors and bipolars and amacrine cells between bipolars and ganglion cells.
The total area occupied by the receptors in the back layer that feed one ganglion cell in the front layer, directly and indirectly, is only about one millimeter
high degree of convergence, together with more direct path in and near fovea (one cone—>one bipolar—>one ganglion cell) can explain the 125:1 ratio of receptors to optic nerve fibers without having really bad vision.
Layers of the retina
- Three main cell body layers (photoreceptor cell bodies, inner nuclear layer, and ganglion cell layer)
- Two main synaptic transmission layers (outer plexiform and inner plexiform)
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Phototransduction
- Unlike most sensory system neurons, photoreceptors do not exhibit action potentials– light causes a graded change in membrane potential that changes the rate at which neurotransmitter is released.
- Within the retina projections are rather short– do not need action potentials.
- Light absorption leads to hyperpolarization of the photoreceptor. This leads to less release of neurotransmitter to the post-synaptic cell.
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Cones and rods hyperpolarize in response to light
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What does light do?
- In the dark, the resting potential of the photoreceptor is -40 mV.
- Light shining onto outer segment leads to the hyperpolarization of the photoreceptor and reduction of neurotransmitter released.
- In the dark the number of Na⁺ channels open at the synaptic terminal is relatively high, and therefore the rate of neurotransmitter release is high. In the light the number of open Na⁺ channels is reduced and rate of neurotransmitter release is reduced.
- Of course, this seems kind of backwards compared to what you’ve have learned thus far.
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cGMP gated Na⁺ channels are key
in dark channel open due
to cGMP binding.
Na⁺ rushes in
cell depolarized
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In the dark
- cGMP gated Na⁺ channels in outer segment are open allowing ions to flow inside the cell. This leads to a resting potential of -40 or so.
- The probability of these channels being open is regulated by the levels of cGMP.
- In the dark, high levels of cGMP keep the channels open.
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In the light
- A photon of light is absorbed by photopigment (retinal or retinaldehyde, an aldehyde of Vitamin A) that is coupled to a protein in the outer segment called opsin. Absorption causes a change in conformation of retinal that in turn changes the conformation of opsin.
- This leads to the disassociation of trimeric G-proteins (special α subunit called transducin) from the receptor.
- Transducin activates a cGMP phosphodiesterase which degrades cGMP to GMP. Channel opening probability decreases, cell gets hyperpolarized.
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Phototransduction
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Vertebrates typically have four cone opsins (LWS, SWS1, SWS2, and Rh2)
from: https://en.wikipedia.org/wiki/Opsin
long-wave sensitiveLWScone500–570 nmgreen, yellow, redOPN1LW "red" / OPN1MW “green"
short-wave sensitive 1SWS1cone355–445 nmultraviolet, violetOPN1SW "blue"
short-wave sensitive 2SWS2cone400–470 nmviolet, blue(extinct in therian mammals)
rhodopsin-like 2Rh2cone480–530 nmgreen(extinct in mammals)
rhodopsin-like 1 (vertebrate rhodopsin) Rh1rod~500 nmblue-greenOPN2 = Rho = human rhodopsin
Like type II opsins, type I opsins have a seven transmembrane domain structure similar to that found in eukaryotic G-protein coupled receptors.
- but these can be proton pumps (bacteriorhodopsin), chloride pumps (halorhodopsin), channelrhodopsin (ChR), archaerhodopsin (Arch)
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are used by various bacterial groups to harvest energy from light to carry out metabolic processes using a non-chlorophyll-based pathway
- serve them as light-gated ion channels, amongst others also for phototactic purposes
Type II opsins (or animal opsins) are seven-transmembrane proteins (35–55 kDa) belonging to the G protein-coupled receptor (GPCR) superfamily
Phototransduction in rod photoreceptors
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cGMP, cyclic nucleotide gated channel
Title Text
http://courses.pbsci.ucsc.edu/mcdb/bio125/Animation11-02Phototransduction.mov
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Signal amplification
- One photon of light can activate 800 transducin molecules. This leads to about 800 phosphodiesterases activated. Each phosphodiesterase cleaves 300 or so cGMPs/second. This can result in the closing of about 200 ion channels (2% of total). 106–107 Na⁺ ions per second are prevented from entering the cell for a period of ~1 second.
- Changes membrane potential about 1 mV.
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~30 mV working (dynamic) range for photoreceptors. But adaptation scales this to work for different background light levels.
Need to inactivate opsin signaling after a light flash
- Rhodopsin kinase/arrestin– activated rhodopsin can be phosphorylated by a specific kinase and intracellular Ser/Thr residues. This creates binding sites for arrestin which binds and prevents the activation of transducin.
- All-trans retinol gets shed, transported to pigment epithelium cells, changed to cis-retinol and reincorporated into opsin.
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Light adaptation– or how do we adjust to different light intensities?
- There is a million times more photons in a bright sunny day than at starlight and yet we can detect difference in light intensity under both conditions.
- Because at low levels of light more channels close per photon than at higher levels of light. Therefore, as light levels increase it takes more photons to close the same number of channels.
- This is due to the changes in the intracellular Ca²⁺ levels. Ca²⁺ can come in through Na⁺ channels. When they close (in the light), Ca²⁺ levels decrease. This does a number of things to make it harder to close more channels with each new photon. 1. Ca²⁺ normally inhibits guanylyl cyclase, lower Ca²⁺ in light leads to more cGMP. Therefore more PDE activation is needed to reduce cGMP levels and close more channels. 2. Ca²⁺ also inhibits rhodopsin kinase. Lower Ca²⁺ levels activates more kinase. With more kinase the activated opsin becomes inactivated. Leads to less PDE activation per photon, less channels closed per photon.
- This prevents us from saturating our photoreceptors and thus allows us to see changes in illumination over a wider range of light intensities.
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The retinoid cycle and photoadaptation
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Cell types of the retina: photoreceptors
- Rods and cones– have an outer segment comprised of membranous disks that contain photopigment and an inner segment that contains the cell nucleus and synaptic terminals.
- The absorption of light by photopigment in outer segment initiates a signal transduction cascade that changes the membrane potential of the cell, and therefore the amount of neurotransmitter released plus or minus light energy.
- Photoreceptors synapse with bipolar cells and horizontal cells in the outer plexiform layer.
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Rods and cones
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Structural Differences Between Rods and Cones
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Why the cone shape? Shape of cone preferentially accepts light directed straight into the eye through the pupil instead of off axis. Known as the Stiles–Crawford effect.
EM section through a kangaroo rat rod cell
stalk
Outer segment
Inner segment
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Rods and cones are distinguished by:
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shape
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type of photopigment they contain
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distribution across the retina
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pattern of synaptic connections
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specialized for different aspects of vision
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Rod system– low spatial resolution but extremely sensitive to light
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Cone system– high spatial resolution but is relatively insensitive to light.
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Range of luminance values over which the visual system operates
- Rods– used mostly for dim light to almost indoor lighting
- When only rods are used called scotopic vision. Not very good.
- Cones dominant in visible light. Called photopic.
- Twilight uses both called mesopic vision.
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More factoids
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Rods produce a reliable response to a single photon of light, it takes over a 100 photons to produce a comparable response in a cone.
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Cones adapt better than do rods– about 200 ms for a cone, 800 ms for a rod.
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Rods synapse onto specific bipolar cells (rod bipolars) that synapse onto amacrine cells which contact both cone bipolars and ganglion cells. Cones go bipolar to RGC directly.
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Rods exhibit convergence– many rods synapse onto a single bipolar cell, many bipolars onto a single amacrine cell.
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Cones can be 1 cone - 1 bipolar - 1 ganglion cell
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Differential responses of human rods and cones
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cone response over in about 200 ms, whereas the rod response can continue for more than 600 ms.
from https://en.wikipedia.org/wiki/Adaptation_(eye):
The human eye can function from very dark to very bright levels of light; its sensing capabilities reach across nine orders of magnitude. This means that the brightest and the darkest light signal that the eye can sense are a factor of roughly 1,000,000,000 apart.
in any given moment of time, the eye can only sense a contrast ratio of one thousand.
the eye adapts its definition of what is black.
takes approximately 20–30 minutes to fully adapt from bright sunlight to complete darkness and become ten thousand to one million times more sensitive than at full daylight
takes approximately five minutes for the eye to adapt to bright sunlight from darkness
Dark adaptation is far quicker and deeper in young people than the elderly
Rods and cones are not distributed equally in the retina
- Human retina– 91 million rods, 4.5 million cones.
- In most places the density of rods exceeds that of cones.
- Changes dramatically in the fovea, central retina (1.2 mm in diameter).
- Cones increase in density 200 fold, become highly packed. Center of the fovea, called foveola is totally rod free.
- Gives high visual acuity, which decreases rapidly away from the fovea.
- Reason why we are constantly moving our heads to center our eyes toward what we want to look at.
- Reason why it it best to see a dim object by looking away from it.
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Distribution of rods and cones in the human retina
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Retinal disease
Loss of peripheral retina, Rods
Loss of photoreceptors in the macula, cones
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Distribution of rods and cones in the human retina
- Other cell layers are displaced in the fovea. Allows light to hit cones with less interference.
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Cones and color vision
- 3 types of cones, each having different absorption spectra- called blue (S-cones), green (M-cones), and red (L-cones) opsin.
- Most people can match any color by changing the intensities of these three colors (RGB).
- 5-6% of males are color blind- due to mutations in the red or green opsins. They are X-linked and near each other.
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Cone absorption spectra and distribution in the retina
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Many deficiencies of color vision are the result of genetic alterations in the red or green cone pigments
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Many deficiencies of color vision are the result of genetic alterations in the red or green cone pigments
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Color blindness
http://www.prokerala.com/health/eye-care/eye-test/color-blindness-test.php
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Rods and cones
Rods
- 90 – 120 million
- Peripheral vision
- Located everywhere except fovea
- Very sensitive to light
- Used in low light situations
- One type
- Highly convergent
- Black and White
Cones
- 4-6 million
- Central vision
- High density in the macula and fovea
- Less sensitive to light
- Most normal lighting conditions
- Three types
- Nonconvergent
- Color vision
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Other cell types of the retina
- Bipolar cells– cell bodies in the inner nuclear layer. Gets info from photoreceptors in outer plexiform layer and transmits it to ganglion cells and amacrine cells in inner plexiform layer. Rods and cones use specific types of bipolars.
- Ganglion cells– cell bodies in ganglion cell layer. Output neurons of the retina. Receives info from bipolar and amacrine cells and sends it out through the optic nerve.
- Horizontal cells– cell bodies in inner nuclear layer. Makes multiple contacts with photoreceptors and bipolar cells. Largely responsible for luminance contrast.
- Amacrine cells– cell bodies in inner nuclear layer. Makes contact in the inner plexiform layer with bipolar cells and ganglion cells. Several distinct subclasses. Coordinate ganglion cell activity. e.g. motion
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- luminance contrast = luminance difference/average luminance
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same as antagonistic center-surround RFs
Retinal ganglion cells (RGC)
- RGCs are the cell that sends action potentials to the brain.
- Much of the information in vision has to do with changes in light intensity. Example black and white movies.
- In order to understand how the brain makes sense of the differences in light intensity that the eye sees, it is important to know what makes RGCs fire.
- Record from an RGC and shine light onto different photoreceptors. Find:
- Even in the dark RGCs are spontaneously active.
- Receptive fields of RGCs are circular. Smaller in the center of the retina and bigger in the periphery.
- Find two classes of RGCs. Those that have receptive field profiles that are ON center and those that are OFF center.
- The receptive fields of RGCs overlap so that multiple RGCs see each point of space.
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Stephen Kuffler 1950s
- Measured the action potentials from specific RGCs after shining light on the retina.
- Determined that RGCs have receptive fields. Found that a receptive field can be divided into center and a surround.
- Ganglion cells come in two types- ON-center/OFF surround and OFF-center/ON surround, in roughly equal proportions.
- ON center RGCs fire more when light that hits the center is brighter than that of the surround and fire less when it is darker in the center than in the surround. OFF center fire less when it is brighter in center and more when it is darker in the center.
- Acts like having separate luminance channels. Changes in intensity whether increases or decreases, are always conveyed by action potentials. RGCs are not photodetectors but are detecting the contrast between areas.
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On and Off center RGCs
When light goes on-depolarizes
When light goes on- hyperpolarizes
Off response
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On- and off-center retinal ganglion cell responses to stimulation of different regions of their receptive fields
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On- and off-center retinal ganglion cell responses to stimulation
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Responses of On-center ganglion cells whose receptive fields are distributed across a small spot
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Responses of On-center ganglion cells whose receptive fields are distributed across a light-dark edge
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Run that by me again
- For an ON- center/OFF-surround RGC, a point of light that fills the entire center but not in the surround will give maximal stimulation (increased action potentials). i.e. brighter in center than in surround.
- A point of light in surround but not in the center will hyperpolarize the RGC (reduce baseline spike rate).
- Light that crosses into both will be in the middle depending on the relative amounts.
- Both center and surround illuminated is basically the same as being in the dark (background levels).
- RGCs fire depending on contrast, not by absolute light intensity.
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Responses of On-center ganglion cells based on changes in center intensity
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Title Text
http://courses.pbsci.ucsc.edu/mcdb/bio125/Animation11-03InformationProcessingintheRetina.mov
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ON and OFF RGCs
- Have dendrites that arborize in separate strata of the inner plexiform layer, forming selective synapses with different types of bipolar cells. ON in sublamina A and OFF in sublamina B.
- Synapse with bipolar cells. Bipolar cells do not use action potentials, but use graded potentials to release transmitter.
- There are two types of bipolar cells– ON center and OFF center. OFF center uses AMPA receptors (ionotropic) that cause the cell to depolarize in response to glutamate released by photoreceptors. ON center use metabotropic glutamate receptors that lead to the closing of Na⁺ channels and hyperpolarize the cell.
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On and Off center RGCs
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Circuitry responsible for generating receptive field center responses
- Light hits cone causes hyperpolarization of cone, leads to less release of glutamate.
- Two bipolar cells synapse with cone, an on-center and off center bipolar cell.
- On center bipolars are normally inhibited by glutamate, less glutamate, less inhibition, more release of neurotransmitter onto RGCs which increases of on-center RGC firing.
- Off center bipolars are normally activated by glutamate, become hyperpolarized, decrease transmitter release, which leads to a decrease in firing rate of Off-center RGCs
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Light in center causes ON ganglion cells to increase firing rate and OFF ganglion cells to decrease their firing rate
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Explain the graphs better. Make the distinction of graded potential vs. action potentials
Horizontal cells create circuitry that is responsible for generating the antagonistic surrounds of RGCs
- Light hitting surround cones hyperpolarizes causing less glutamate to be released onto horizontal cell dendrites.
- Horizontal cells hyperpolarize because of less glutamate (have AMPA receptors) and decrease their rate of transmitter release (GABA) onto the synaptic terminals of the nearby photoreceptors.
- Horizontal cells normally inhibit cones (use GABA), thus now cones are less inhibited (depolarized), and release more glutamate than without surround.
- This leads to a depolarization of off-center RGCs, causing them to increase their firing rate.
- And hyperpolarizes on-center RGCs, causing them to decrease their firing rate.
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Circuitry that generates the antagonistic surrounds of retinal ganglion cell receptive fields
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A bunch of photoreceptors, but all the 1-1-1 circuits are overlapping giving series of slight shifted center-surround receptive fields.
Circuitry that generates the antagonistic surrounds of retinal ganglion cell receptive fields
- Light hits cone in surround
- Less glutamate released on horizontal cell
- Horizontal cell is hyperpolarized, releases less GABA onto cone in center. This depolarizes center cone relative to before light.
- More glutamate released by center cone to ON and OFF bipolars.
- Off-center depolarized, on-center hyperpolarized.
- Off-center ganglion cell fires more
- On-center fires less.
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Circuitry that generates the antagonistic surrounds of retinal ganglion cell receptive fields
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The Hermann grid illusion
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Explanation of the Hermann grid
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Summary
- Light falls on photopigment, that is transformed to action potentials that ganglion cells convey to the brain.
- Phototransduction occurs in rods and cones that have different properties that meet the conflicting demands of sensitivity and acuity.
- RGCs have a center-surround arrangement of receptive fields that makes them good at contrast detection and relatively insensitive to background illumination.
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