Sensory Physiology - Exam 2

Human eye acts as a single thin lens

- A converging lens refracts light, and parallel rays converge at a distance known as the focal length - The power of the lens is 1/f; more power --> small f - The image distance is the distance behind the lens where light scattering from a particular point on an object and hitting the lens at various angles, then converges - Retinal image is upside down and right-left reverse - For clear vision, projected image must fall onto the retina; image distance fixed ~20 mm

Some vertebrates have a tapetum lucidum

- A reflextive layer of tissue made or mirrored crystals under the retina - Any photons not absorbed by photoreceptors are reflected and get a second chance to be absorbed by the photoreceptors - It gives some animals' eyes an eyeshine in the dark - It is found in nocturnal vertebrates

R-opsins signal differently than classic vertebrate C-opsins - ciliary

- A single photon closes 3-5% of the rod CNG channels; to save energy in the dark, these channels have low Po and conductance so that the dark current is small; the amplitude of the peak response is very precise; single photons are poorly detected by cones - Latency is slower - Have a relatively limited dynamic range

Transducin mechanism

- Activated PDE6 which cleaves cGMP - Loss of cGMP leads to the closing of CNG channels This reduces the dark current

Resolving power

- Acuity - the ability to distinguish two closely space objects - As you move further from two objects, angular separation decreases - Acuity is the smallest angular separation that the eye can resolve - Depends on distance between photoreceptors; higher density=better resolution - Need either larger f or smaller s; why animals with good vision need larger eyes

Adaptation

- Adaptation to light restores some of the dark current seen in the dark condition - This allows them to be sensitive to further increases in light intensity; increases the dynamic range - This occurs primarily in cones; rods are mostly saturated in bright light - In prolonged light, the lowered internal Ca levels leads to adaptation which activated guanylyl cyclase to make more cGMP

The V1 cortex is organized into vertical orientation columns

- All cells within vertical column will share the same orientation column and ocular input - No really quite so ice-cube like; they form pinwheels

Large and ancient family of opsin proteins

- All opsin absorb light with retinal, and have similar three dimensional structures - Not all opsins are GPCRs, however; some may signal with ion channels

R-opsins are bistable, unlike C-opsins

- Bleached - can't absorb another photon until retinal is released and new cis-retinal is bound - The idea is that you don't have to spend energy to replace it; there is a time delay because of the long pathway

Type 4: V1 blobs

- Blob neurons have concentric center-surround receptive fields sensitive to color - They are particularly frequent in layers 2/3 - More complex with double-opponent

Animals opsins fall into three major classes

- C, GO, and R opsins - Each opsin class interacts with the same chromophore (retinal), but each undergoes a different cycle with light

Two major types of photoreceptors in animals

- Ciliary - membrane invaginations found above the basal body of a cilium; usually use C-opsin or G0- opsin; generally light hyperpolarizes - Rhabdomeric - microvilli found off the cell body; usually use R-opsin; generally light depolarizes; don't usually need RPE layer to regenerate retinal

Many ganglion cells show color-opponency

- Color adds a layer of complexity to the wiring of the same ON/OFF bipolar cells - In the fovea, horizontal cell connections to form surround are not at random for a given midget bipolar cell - Have some color that best activates the center of their field because of the one cone feeding into the center of field - Color opponent cells may not want color in periphery

Vertebrate Cones vs Rods

- Cones have an invaginated membrane; their outer segment is triangular - Rods have free floating membranous discs within a limiting membrane; their outer segment is shaped like a cylinder; rods are unique to vertebrate eyes - Opsin is found in discs at very high concentrations - Photoreceptor cells have a large amount of membrane in their outer segment -Rods have >1000 discs with 10^8 rhodopsin molecules per cell; increases the chance a light particle will be absorbed by a photopigment

Mutations in opsin photopigments cause color-blindness

- Deuteranope - loss of green - Protanope - loss of red - Tritanerope - loss of blue - You need two inactive copies to cause these color blindness - Color blindness is sex-linked - It is much more frequent in males than females because red and green opsins are found on the X chromosome

Periphery

- Diffuse bipolar cells can receive input from multiple cones and or rods - Ganglion cell integrates activity of multiple cone bipolar cells to form the center of the receptive field - Larger ganglion cell receptive fields

The V1 cortex is organized into ocular dominance columns

- Extend vertically from V1 to V6 - Some cells respond to both eyes, but have preference - Development depends on input during critical period

Vision problems often caused by problems with accommodation

- Far-sighted - lens too flat; can't focus on near objects well - Near-sighted - lens too globular; can't focus on distant objects well

Fovea 2

- Ganglion cells have a smaller receptive field - Each cone connects to 2 midget bipolar cells; these connect to 1 ganglion cell - Ganglion cells also receive indirect information from surrounding cones - Almost 1:1 relationship between midget bipolar cell and cone

Theoretical evolution of camera eyes

- Generally, we classify eyes on a scale of complexity - The absolute simplest eye would be a single cell that is photosensitive and has a shading pigment - The next step is two-celled eyes: one photoreceptor and one pigment cell - A pigment cup eye or optic cup can detect the direction of light in a rudimentary fashion - If enclosed sufficiently, this can lead to a pinhole eye or pit eye, which allows for rudimentary image formation

Features of camera eyes

- Have a single lens that focuses light onto the back of the vitreous chamber - Light is detected by an array of photoreceptor cells - Shifting the shape of the lens shifts where the light is focused

Types of color opponent - midget GC

- High acuity - Necessary for the perception of color and form - Mostly receive info from red/green cones - Found mainly in fovea - Weaker responses to contrast/low light - Relatively slow responses; but can stay stead

How is the center-surround receptive field generated?

- Horizontal cells are critical for generating center-surround receptive fields - They receive synapses form photoreceptors over a wide area - This large receptive field allows them to respond to the average level of illumination over a relatively large area - Average out responses over large area of retina - Electrically coupled to increase the size of their receptive field; mediated by gap junctions

Grandmother cell

- Hypothetical neuron that activates when a complex but specific concept or object is presented in any sensory modality - The number of objects that could be recognized would be limited by the number of neurons - Alternative - distributed representation theory

Some animals can detect IR

- IR radiation is one way heat is transferred from one object to another - Everything with temperature above 5K emit electromagnetic radiation

Variations among vertebrate cones - Oil droplets

- In birds, reptiles, and non-placental mammals - In bird, cones can contain either red, yellow, or transparent oil droplets - Sharper, more focused colors; not advantageous in low light because some light is lost, thus most often seen in diurnal animals - Can act as a microlens to focus light onto the outer segments - Some filter particular wavelengths of incoming light

Recovery from adaptation

- In light, most rods have fully activated rhodopsin and most CnG channels are closed; cones are adapted to an intermediate state - When initially moved to low light levels, cones respond slightly; rods can't respond because retinal is mostly bleached - As retinal is recovered and rhodopsin re-formed, rods start to respond; this takes 20-30 mins; the cones slightly increase their sensitivity over 5-10 minutes, but they are not particularly sensitive to light and have a high threshold

Dark current: rods are depolarized in the dark

- In the dark, there is enough cGMP to open CNG channels - They are non selective cation channels and allow Na and Ca to enter the cell; most of the current is mediated by Na; called the dark current - This has the effect of depolarizing the rod, such that it releases vesicles continuously in the dark - Na ions are pumped out by the Na/K pump in the inner segment to maintain ion concentrations - Activation of transducin, caused by light, has the net effect of hyperpolarizing the cell

Directional selectivity

- Inputs to the V1 neurons are such that their best stimulus is a bar at a particular orientation moving in a particular direction across their receptive field - These V1 neurons respond to a moving bar/edge - Object must be within receptive field

What is the function of the LGN?

- LGN is a relay station in the thalamus - Each LGN neuron receives input from a few retinal ganglion cells, and each ganglion cell contacts a few LGN neurons - LGN neurons have center-surround receptive fields similar to the ganglion cells that innervate them - Helps to align retinotopic maps

The LGN is highly stratified and strictly organized

- LGN neurons have monocular input; layers 2, 3, 5 ipsilateral; layers 1, 4, 6 contralateral; input from each eye strictly segregated into different layers - Input from different types of RGCs are segregated; Parasol GCs synapse on large-bodied magnocellular cells; Midget GCs synapse on small/medium bodied parvocellular cells; Bistratified cells synapse on very small-bodied koniocellular cells - There is a retinotopic map within the LGN; neighboring positions in space are detected by neurons neighboring each other in LGN

Hypercolumns

- Larger organizational units - Chunk of cortex that contains neurons with approximately the same receptive field location in space - This collection of neurons will have: all possible orientation selectivities, both eyes represented, all possible direction selectivities

Inverted retina

- Light passing through all layers before reaching photoreceptors - Not ideal because it increases light scattering - Creates a blind spot where the ganglion cell axons leave the retina

Image-forming eyes

- Likely to have evolved from more primitive eyes, whose primary role was in non-image forming functions

Animals have circadian rhythms set by light

- Mammals have an intrinsic activity bodily rhythm, but it is not on a 24 hour cycle - The 24 hour rhythm is set by light - If rods and cones were genetically ablated in mice, the circadian rhythm persists - Light that regulates circadian rhythm sensed by melanopsins in intrinsically photosensitive retinal ganglion cells

Types of color opponent - bistratified

- Medium receptive field - Moderate speed - Respond to blue/yellow and moderate contrast Their vertical pathway is less clear - Only in primates

Gap junctions between many cell types in the retina

- Most gap junctions spread information horizontally - Gap junctions increase the size of receptive fields and allow light levels to be integrated over the retinal surface - Integration increases light sensitivity, which is important in low light conditions - Integration decreases visual acuity, so the opening of gap junctions is regulated by light levels - Many retinal gap junctions contain the protein Cx36

More than 22 morphological types of amacrine cells

- Most have large receptive fields - Different types of NTs released - All-type amacrine cell receives input from rod bipolar cells - Receive input from bipolar cells - Transmit information to bipolar cells, ganglion cells and other amacrine cells, depending on the amacrine cell type

Different vertebrates have different types and numbers of opsins

- Most mammals only have two cone opsins; humans have three - Duplication of long way opsin became green opsin; this is why the red and green opsins are so similar - Ancestral vertebrate had four cone opsins and rod opsin - There is an advantage for detecting ripe food, sexual selection, and predation - Except for primates, most mammals only have two photopigments - Visual acuity is lost when an opsin is lost; you need the contrast between red and green

Four major classes of V1 cortical neurons

- Neuron classes are distinguished by their preferred visual stimuli and localization within a vertical column - Layers 2/3 have hypercomplex cells and center-surround blob cells - Layer 4 has simple cells - Layer 5/6 have complex cells

Orientation selectivity

- No stimulus in receptive field, no response - Preferred stimulus, large response - Non-preferred stimulus, no response - Neighboring LGN cells project to same V1 cells - Activate multiple LGN cells at once

Cells and layers of the retina

- Nuclear layers contain cell bodies - Plexiform layers contain processes/synapses - Vertical flow of information: cone --> bipolar --> ganglion cell - Horizontal and amacrine cells are inhibitory neurons making horizontal connections

Bipolar cells and RGCs have center surround receptive fields

- ON bipolar cells/ganglion cells respond best to a light image on a dark background in a small region of the visual field - They respond best to particular types of contrast - All bipolar cells have center-surround field - OFF bipolar cells/ganglion cells respond best to a dark image on a light background

Bipolar cells have center surround receptive fields

- ON/OFF describes effect of light falling in center of cones' receptive field - Light falling on surrounding areas has the opposite effect - Retinal ganglion cells also have center surround receptive fields - They receive excitatory input from the corresponding type of bipolar cell

Signaling cascade allows for enormous amplification

- One rhodopsin molecule absorbs one photon - 10^3 G-protein molecules are activated - 10^3 cGMP phosphodiesterase molecules are activated - 10^5 cGMP molecules are hydrolyzed - 300 cation channels close - 10^6-7 Na ions per second are prevented from entering the cell - Membrane potential is altered by 1 mV

Information from V1 goes to the dorsal and ventral stream

- Parallel processing - color perception, motion perception, depth perception, and face recognition - Dorsal pathway - input from V3; used for analysis of spatial location relative to viewer, motion, and in action planning - Ventral pathway - input from V4; used for object discrimination and categorization

Parasol ganglion cells do not show strong color opponency

- Parasol GCs receive input from many rods and cones - They are necessary for perception of movement, depth, and contrast - They function well in low light levels - Exact colors do not matter - Processed more upstream

Midget vs Parasol

- Parasol ganglion cells have a larger receptive field - Parasol much larger than midget - Parasol found in periphery and midget found in fovea

Information from the retina flows through the optic nerve to the brain 2

- Partial decussation (crossing) of the retinal ganglion axons occurs in primates at the optic chiasm - With forward facing eyes, each eye receives input from both halves of the visual field - Thus, LGN only processes information about half of the visual field; information from right visual field of both eyes sent to left LGN and vice versa - Mammals with eyes on the side of their heads exhibit complete decussation because there are two separate visual fields

Photopigment

- Photoreceptor proteins consisting of an opsin protein molecule and retinal - Opsin is a 7TM protein

R-opsin signaling

- R-opsin phototransduction pathway is very similar to that in many mammalian taste receptor cells - Positive feedback loop with calcium entering through TRP channel inducing further opening of TRP channels, either directly or through Ca induced Ca release from the ER - Upside - this leads to fast and explosively large response - Downside - exact latency and peak response tend to be variable - Example: vertebrate melanopsins

Type 2: V1 complex cell

- Respond best to elongated bars or edges in a particular orientation - Are usually binocular - Spatially homogenous receptive fields - Exhibit length summation - Some are direction selective - Majority of cells

Type 1: V1 simple cell

- Respond best to elongated bars or edges in a particular orientation - Can be monocular or binocular - Receptive field has separate ON and OFF subregions - They exhibit length summation = larger responses with increasing bar length Some are direction selective - Minority of V1 cells

Fovea

- Retinal region of the highest acuity in the daytime - Other retinal layers are moved out of the way in the fovea so that light can directly hit the photoreceptors - Has few rods - Cones expressing red (64%), green (32%) and blue (2%) distributed randomly

Vertebrate Cones vs Rods 2

- Rod outer segments are longer than cones - Rods express rhodopsin photopigment=rod opsin + retinal - Different cones express different photopsin photopigments = red + retinal; blue + retinal; green + retinal

Rods signal indirectly to retinal ganglion cells

- Rods act to increase sensitivity of their neighboring cells - Fovea - acuity over sensitivity; midget bipolar cells and ganglion cells have small receptive field and receive little rod input - Periphery - sensitivity over acuity; diffuse bipolar cells and ganglion cells have larger receptive fields and integrate information from many cones and rods - All ganglion cells receive some input from cones

Vertebrate Cones vs Rods: sensitivity

- Rods are very sensitive and can respond to very dim light; however, they are bleached in intense light because they cannot adapt well - Cones are less sensitive, but different cones detect different wavelengths of light - After long periods in the dark, rods have much lower threshold than cones

Differences in signaling between rods and cones

- Rods only directly connect to ON bipolar cells - Rod bipolar cells signal indirectly to ganglion cells through amacrine cells - Rods signal indirectly to ganglion cells through electrical synapses with cone photoreceptors

What is meant by ON and OFF cells?

- Sign conserving OFF bipolars - glutamate opens ionotropic glutamate receptors and causes depolarization - Sign inverting ON bipolars - glutamate activates a metabotropic glutamate receptor that initiates cascade that causes hyperpolarization - In the dark, cones release glutamate - Glutamate activates a metabotropic glutamate receptor --> closes TRPM1 - TRPM1 is a non-selective cation channel, so this hyperpolarizes the bipolar

Type 3: V1 end stopped cell

- Similar to complex cells, but have end stopping, not length summation - End stopping means that their best bar stimulus has an optimal length

How is the center-surround receptive field generated? 2

- Surround cones are depolarized if their receptive field is dark - The cones continue to release glutamate, which depolarizes horizontal cells - Horizontal cells make wide connections and inhibit center cone pedicles - Center cones release less glutamate as if they are hyperpolarized - Greatest suppression of glutamate release when center cone is in light and surround is in the dark

Retinitis Pigmentosa

- Symptoms include difficulty seeing at night and a loss of peripheral vision; typically starts in childhood; eventually most people become blind - Involves breakdown and loss of cells in the retina, particularly rods; degenerating rods are phagocytosed by the RPE and this leads to a heavy pigmentation of the retina

Different human opsin absorb different wavelengths

- The opsin protein itself is what respond to different wavelengths - The red and green opsins are very similar to each other - Because of these small differences in retinal, they respond different

Chromophore

- The part of a pigment molecule that absorbs selective wavelengths of light and thereby changes the color of the light - Retinal is a chromophore that absorbs light; chlorophyll another example - There are different functional groups that absorb different wavelengths

Deactivation

- The retinal regeneration is slower than the activation by light - In the dark, many CNG channels are open - When initially moved to light, many CNG channels close - Closure of CNG channels lowers internal Ca levels - Lowered Ca leads to deactivation over a short time period

Retinal Pigment Epithelium

- The tips of the photoreceptor outer segments are embedded into the retinal pigment epithelium - The RPE lies between the photoreceptors and the choroid layer - Recycles retinal from rods - groups of 30-40 discs are taken at a time - Has melanosomes that absorb light not absorbed by the photoreceptors - increases visual acuity - Involved in photoreceptor disc shedding - new discs made at the base; takes about 10 days from synthesis to removal - Controls flow of fluid/nutrients/molecules into the retina

Cells and layers of the retina 2

- There is not a simple relay of information from photoreceptors to retinal ganglion cells - The exact connections vary between different species - The information is processed, such that the photoreceptors report different information than bipolar cells and RGCs; they have different receptive fields - The receptive field of a retinal cell is the portion of the visual field to which it respond - Cone photoreceptor cells make synapses onto two types of bipolar cells: ON and OFF - Cone bipolar cells make excitatory synapses onto retinal ganglion cells: ON and OFF - Both types of RGCs project to the brain; this is an example of parallel processing - Although all three types of cells are neurons, only RGCs fire action potentials; others have graded release

Most V1 cells show orientation selective receptive fields

- They respond strongly to lines, bars, or edges of a particular orientation but not to the orthogonal orientation - The object must be within their receptive field

Variations among vertebrate cones - twin and double cones

- Twin cones found in some fish - Double cones seen in many vertebrates, but not placental mammals - Sometimes find triple and quadruple cones - Twin and double cones are closely apposed along a large part of their inner segment; out segments are separated - Have extensive connections through gap junctions; electrically coupled - Proposed to have achromatic functions

V1 Striate Cortex

- V1 cells integrate and transform LGN information unlike LGN cells - They can be orientation selective and direction selective

Line of Gennari in primate striate cortex

- V1 is a six layered cortex, like other cortical regions - The line of Gennari is in layer 4 where the myelinated axons from the LGN enter - There is a white line due to the large number of myelinated axons - Isomorphic representation means equal representation of the visual field; fovea over represented - V1 also has a non-isomorphic retinotopic map

R-opsins signal differently than classic vertebrate C-opsins

- Vertebrate rods and cones - retinal activation --> signal amplification --> current decrease --> hyperpolarize - Many invertebrate photoreceptors - retinal activation --> phototransduction --> current increase --> depolarization - Both use retinal chromophore attached to an opsin protein to form the photopigment - Tends to be explosive in response

Bipolar/ganglion cells respond best to edges/contrast due to their center surround receptive fields

- Vertebrate vision depends on seeing the contrast between images and background - ON bipolar receptive field --> excitation from dark in periphery, but inhibited by dark in center --> little to no response - ON bipolar receptive field --> inhibition from light in periphery, but excited by light in center --> little to no response - ON bipolar receptive field --> excited by light in center, and mixed effect of light and dark on periphery --> bipolar cell responds

Vertebrate C-opsin phototransduction

- Vertebrate visual opsins are GPCRs - Light absorption by retinal causes a conformation change in the opsin - The conformational change in the opsin leads to activation of transducin due to the binding of GTP - Transducin is released and initiates a signal transduction cascade

R-opsins signal differently than classic vertebrate C-opsins - rhabdomeric

- Very sensitive and fast response due to Ca amplification and compartmentalization of signaling cascade in microvilli; a single photon can lead to several nA of current, but the amplitude varies - There is a thresholding mechanism, so the exact latency is variable - Can respond to light over a larger dynamic range - Have pigment photoregeneration - opsin always ready to absorb more light - no bleaching

Visual Phototransduction

- When light hits the photopigment, you go from a Cis form to a Trans form - As a result, since the bond has been changed, it is no longer going to fit in the opsin the same way as before; therefore, the rest of the protein has to move around it - The opsin protein changes shape and becomes activated - Retinal is simply absorbing light and changing its structure, resulting in this change of the opsin - A GPCR signaling cascade then follows

ipRGCs

- intrinsically photosensitive retinal ganglion cells - Receive input from cones and rods like other RGCs, but also are intrinsically sensitive to light, due to their expression of melanopsin - CoCl2 blocks synaptic transmissions - Primarily involved in non-image forming visual functions, such as the pupillary light reflex and circadian photoentrainment - Project primarily to the SCN in the hypothalamus; small nucleus controls circadian rhythms

Deactivation 2

First - opsin receptor deactivation - Recoverin released rhodopsin kinase in absence of Ca - Rhodopsin kinase phosphorylates rhodopsin up to 9 times - Arrestin binds phosphorylated rhodopsin - This prevents rhodopsin from interacting with transducin

Information from the retina flows through the optic nerve to the brain

In mammals: - Majority (90%) of RGN neurons project to the lateral geniculate nucleus in the thalamus - Minority (10%) flows to the superior colliculus in the midbrain In fish, reptiles, and birds - The superior colliculus is known as the optic tectum and most information projects there

Deactivation 3

Second - transducin and PDE deactivation - Transducin hydrolyzes GTP to GDP - Transducin falls off PDE - PDE deactivated - In light, the same cycle occurs, but the transducin is reactivated by opsin and reactivates PDE - Transducin has intrinsic timer that gets rid of GTP

Deactivation 4

Third - cGMP synthesis - Guanylyl cyclase forms cGMP from GTP - cGMP opens the CNG channels - There is an ongoing cycle between cGMP synthesis and cGMP degradation - With light activation, cGMP degradation by PDE is increased, shifting the balance to less cGMP - By turning off PDE, the balance is shifted back to more cGMP