Special senses Flashcards
How does perceived sensation occur?
• Perceived sensation occurs only after impulses are interpreted by the brain. Steps involved in sensory perception include:
o Stimulus-> receptor-> action potential propagation to CNS->interpretation
What is sensation?
o Sensation- detection of physical properties of stimuli (colour, brightness, warmth or sweetness)
What is perception?
o Perception- conscious sensory experience (interpretation of stimuli)
What are psychophysics?
• Psychophysics- the study of the relationship between physical stimuli and their perceptions produced in a human observer
What is a psychometric function? Describe what variables are graphed in a psychometric graph.
o Psychometric function- describes the relationship between the parameter of a physical stimulus and response. Sigmoid function.
When graphed:
• X axis- stimulus intensity
• Y axis- probability of detection (%)
o Found by measuring human perception according to stimulus intensity
What is absolute threshold?
Absolute threshold- the minimum stimulation required to detect a stimulus 50% of the time
Can receptors only detect large amounts of stimulus or can they detect small amounts of stimulus? Give examples
• Many receptors can detect the smallest physical unit of stimulus possible
o Vision: photoreceptors-> single photon detection
o Olfaction: chemoreceptors-> single odorant molecule detection
o Audition: hair cell->motion of only a few angstroms for detection
What are environmental stimuli significant in sensory perceptions?
o Electromagnetic and thermal energy
o Mechanical energy and mechanical force
o Chemical agents
What environmental stimuli are included in the electromagnetic and thermal energy category?
Light Infrared radiation Thermal Electric Magnetic
What environmental stimuli are included in the mechanical energy and mechanical force category?
Sound and sonar Touch and vibration Pressure Gravity Inertia
What environmental stimuli are included in the chemical agents category?
Taste
Smell
Humidity
What are sensory receptors? What can they do and which form can they take?
• Sensory receptors- specialized sensory cells that detect changes inside (interoceptors) and outside (exteroceptors) the body
o Receptors can initiate nerve impulses by opening or closing stimulus-gated channels
o Receptor cells can be neurons (somatosensory/visual) or non-neural cells (hearing/gustatory)
Describe the 5 main groups of sensory receptors
- Photoreceptors
- Mechanoreceptors
- Thermoreceptors
- Chemoreceptors
- Nociceptors
What is the energy handled by photoreceptors? Give an example.
Energy handled: Visible light
Example: Vision
What is the energy handled by mechanoreceptors? Give an example.
Energy handled: Mechanical- pressure or physical displacement
Example: Proprioreceptors in joints, receptors for hearing and equilibrium
What is the energy handled by thermoreceptors? Give an example.
Energy handled: Changes in temperature
Example: Heat or cold
What is the energy handled by chemoreceptors? Give an example.
Energy handled: Chemical
Example: Taste and smell
What is the energy handled by nociceptors? Give an example.
Energy handled: Tissue damage
Example: Pain
Does every living organism sense the environment in the same way?
No- Animals can use different ways to sense environment around them
How do fish sense their environment?
o Fish emit electrical discharges into surrounding water via electric organs
Electrosensory organs detect changes in shape, amplitude or frequency of the electric field. Useful for:
• Hunting and defense
• Communication
• Navigation
How do snakes sense their environment?
o Snakes can sense infrared radiation by using pits on the face
Pits- contain terminals of trigeminal nerves and they contain receptors which are sensitive to heat/infrared radiation
How do bats/dolphins sense their environment?
o Bats/dolphins- echolocation
What are special senses?
o Special senses- their receptors are localised in a particular area (gustatory, olfactory, visual and auditory system)
What are general senses?
o General senses- their receptors are widely distributed in the body (pain, touch, pressure and proprioception-somatosensory system)
What is sensory transduction?
o Conversion of environmental energies into signal understood by body (change in membrane potential)
Describe the process of sensory transduction (generally)
o When the sensory receptor interacts with the adequate stimulus, it will produce a conformational change in the receptor and produces a change in conductance (G- membrane becomes more permable to specific ions)
Conformational change can lead to the opening of a channel within the receptor itself OR
Can also lead to activation of second messenger cascade that leads to either the opening or closing of a membrane channel
o Influx/eflux of the ions generates a receptor/generator potential
Chang in membrane potential is the important part- doesn’t matter if the change is a depolarisation or hyperpolarisation
o Conversion of energy of stimulus into electrical signal
o Receptors produce graded potentials
o Response will be passed to postsynaptic cell
o Neurons further down the circuit will produce action potentials that will carry information to rest of CNS
o When signals reach cerebral cortex and are interpreted, produces awareness of stimulus
What are 3 different transduction channels?
o Cyclic nucleotide gated channels o TRP (transient receptor potential) channels: o Other channels Piezo
What are two types of cyclic nucleotide gated channels and what are their respective sensory systems?
cGMP-> vision
cAMP-> pain
What stimuli do TRP channels respond to?
Temperature Touch Pain Pheromones Taste and other stimuli Osmolarity
Are piezo channels evolutionary conserved in animals and plants or are they recently developed channels?
• Piezos (Piezo1 and Piezo2) are evolutionarily conserved in animals and plants
Do piezo channels have sequence homology to other known ion channel families?
• No sequence homology to other known ion channel families
Where is Piezo 2 expressed?
- Piezo 2 expressed in a subset of DRG neurons that innervate the skin and hair follicles (low threshold mechanoreceptors- lanceolate endings, circumferential endings and Meissner corpuscles)
- Piezo2 is also expressed in Merkel cells (skin touch receptors involved in the detection of light touch)
What is the structure of Piezo proteins and what is known about their sensing mechanisms and structures?
- Sensing mechanisms and structures still unknown
* Have 18 and potentially up to 38 transmembrane spanning domains
What is known about the structure, history and activation mechanisms of TRP channels?
o Highly conserve channels- preserved in worms, flies mice and humans
o 6 transmembrane spanning domains
o Activation mechanisms still unknown
What are TRP channels sensitive to?
o Sensitive to plant derived chemicals (capsaicin, menthol, camphor, cannabinoids etc)
What are Group I TRPs?
TRPC TRPV TRPM TRPA TRPN
What are Group II TRPs?
TRPP
TRPML
Describe where TRPV is found and what it is activated by
- Present in somatosensory system in nociceptors
* Activated by temperature, pH, capsaicin, endocannabinoids…
Are vampire bat TRPV channels different than normal channels? Why/why not? Describe the experiment that found this result
• Vampire bats have splice variant of TRPV1 channel (shorter channel) that activates at lower temperatures compared to normal TRPV1 channel
• Experimental procedure: Hek cells transfected with 2 different isoforms of TRPV channel (normal and vampire bat variant) and observe the temperature at which they are activated
o Temperature range: 24 C, 29 C, 35 C, 42C
Are TRPA channels in rattle snakes the same as normal channels? Why/why not? Describe the experiment that found this
• Rattlesnake adopted TRPA1 (traditionally not sensitive to heat, instead to plant derived chemicals) and have a genetic variation that makes TRPA1 heat sensitive- has lower temperature threshold for activation
• Experimental procedure: Hek cells transfected with 2 different isoforms of TRPA channel (normal and rattlesnake variant) and observe the temperature at which they are activated
o Temperature range: 24 C, 29 C, 35 C, 42C
Why do small stimulus signals have to be amplified?
- Small signals do not have the energy to generate a behavioural response and must be amplified within the organism by its metabolic and neural machinery
- A highly sensitive amplification system would cause problems because living organisms are constantly bombarded by background stimuli such as light, odour and sound, which could saturate the sensory system
What is amplification?
• Amplification- the strengthening of stimulus energy by cells in sensory pathways
How does signal amplification occur in general? Give examples
• Signal amplification can take place in accessory structures (for example ossicles in middle ear) or be a part of the transduction cascade in sensory cells (for example receptor-> GPCR-> AC-> cAMP-> cellular response)
o At each step in the cascade, the number of activated products is much greater than in the preceding step- this is how change in membrane potential can be substantial)
Are receptor responses to a stimulus graded or all-or-none?
- Receptor response to a stimulus is graded (non-regenerative- die out with time and space)
- Some receptors display purely graded responses (generator potential)-
What are generator potentials and how do they different from action potentials?
purely graded responses (generator potential)- responses of varying amplitude proportional to the strength of the stimulus
-action potentials: when threshold is exceeded (all or none)- relatively the same amplitude
What is receptor adaptation? How can receptors adapt?
• Adaptation- change in the strength of a response in the continuous presence of the stimulus
Adapt by:
-Adaptation of signalling cascade
-Adaptation of accessory structure
How do photoreceptors adapt to continuous light?
o Photoreceptor adaptation- adaptation of signalling cascade
In phototransduction, there is a cGMP channel in the membrane
Allows for influx of sodium and calcium
When channel is activated for too long, there is an increase in intracellular calcium concentration
Calcium inside the cell has several targets and it produces a number of responses
• Stimulates cyclase activity that produces GMP
• Increases channel affinity for cGMP
• Affects transduction cascade
o Changes in signalling cascade that lead to adaptation
Why does the Paccinian corpuscle adapt? What stimuli does it respond to and why?
Paccinian corpuscle- respond to touch and pressure
• Pressure on capsule of Paccinian corpuscle deforms fluid-filled layers of capsule
• Stimulate stretch channels which will produce receptor potential
• If pressure is maintained, the inner layers of the capsule slip back and stop exerting the pressure on the axonal membrane and consequently the receptor potential, and hence action potentials, decay
• When stimulus is removed, the deformation produces another wave of activation of channels in membrane of axon, another receptor potential and hence another action potential
• Only responds to onset and offset of stimulus- good to transmit information about changes
What are the two ways in which a receptor can adapt? Give an example for each and the result of these two different ways
• Rapidly adapting- transmit information about changes
o Paccinian corpuscles
• Slowly adapting- transmit information about changes and maintained features of the stimulus
o Pain receptors
How does frequency coding work? Describe the response to a weak stimulus vs a strong stimulus
o Stimulus strength is encoded in the frequency of action potentials
o Weak stimulus will produce a very small receptor potential (graded responses) and produce a small frequency of action potential
o Strong stimulus will produce a much bigger receptor potentials and higher frequency of action potentials
How does population coding work? Describe in terms of the somatosensory system
o Depends on number of receptors activated
For example, in somatosensory system, light pressure will activate only a few receptors while more pressure will activate a large number of receptors
What is a receptive field?
• Area covered by receptors in a sensory unit is a receptive field
What does coding of location depend on?
• Coding of location depends on receptor location
What does acuity depend on?
• Acuity depends on the density of receptors
What is acuity?
o Acuity- ability to discriminate two separate stimuli in a sensory system
What do you need for high acuity?
High density of receptors
Small receptive fields
Low convergence
Describe how convergence of sensory neurons occurs and the result of convergence
o Each receptor picks up information from a specific area
o Sensory neurons converge on single second order neuron
o Receptive field of secondary neuron will be the sum of the receptive field of sensory neurons that converge on it
Hence, secondary neuron cannot discern from which converged sensory neuron the stimulus came from
What is the relationship between convergence, acuity and sensitivity?
o High converge=
Low acuity
High sensitivity
What is the general process for lateral inhibition?
• Stimulus-> responses to stimulus-> inhibition of neighbouring cells-> contrast enhancement
What is the olfactory system? Describe its sensitivity and ability to discriminate
• Chemoreceptive system-highly sensitive and discriminative
Is the olfactory system a new feature of eukaryotes or has it been present for a long time in evolutionary history?
• Structure and function of olfactory system conserved in many eukaryotes
o Evolved from systems designed to detect presence of chemicals in environment
In eukaryotes, what role does the olfactory system play?
o Food search
o Predator and prey detection
o Territory marking
• Role in reproduction (pheromones)
Why can smell of an odour trigger vivid memories very rapidly in a subconscious manner?
• Smell transmits information to old areas of the brain associated with emotion and memory (entorhinal cortex and amygdala)
Where are the olfactory receptors located?
• Receptors in the olfactory mucosa (deep within the nasal cavity)
What are the cells in the olfactory mucosa and what is their purpose?
• In olfactory mucosa, there are:
o Bipolar receptor cells
o Supporting cells- provide structure
o Basal cells- stem cells which replace olfactory sensory neurons when they die (every one or two months)
High specificity of replacement (olfactory receptor replaced by same olfactory receptor)
In anatomical terms, how is an odorant detected and how does this electrical signal make it to the olfactory bulb?
o When we breath, sniffing directs air to olfactory epithelium
o Odorant will diffuse in olfactory mucosa and will dissolve and will contact with olfactory receptors, which are found in the cilia (extensions of apical membrane of bipolar cells) which protrude from olfactory mucosa.
The cilia increase the area of contact of the olfactory sensory neuron with the olfactory mucosa-> increases chances of odorant bumping into olfactory receptor
o Bipolar cells send axon that go through pores in cribriform plate (part of ethmoid bone) and make synaptic contact in the glomeruli (olfactory bulb)
What are the two mammalian olfactory systems?
- Main olfactory bulb system
* Vomeronasal organ
Describe the anatomical pathway and role of the main olfactory bulb system
o Neurons project their axons from main olfactory epithelium and contact postsynaptic cells in the glomeruli in the main olfactory bulb
o Signals from main olfactory bulb go to different brain areas such as the anterior olfactory nucleus, piriform cortex, olfactory tubercle, lateral amygdala, entorhinal cortex
o Involved in detection of volatile substances
Describe the anatomical pathway and role of the vomeronasal organ
o Sensory neurons from main olfactory epithelium are projected to vomeronasal organ which then projects axons to accessory olfactory bulb and axons from accessory olfactory bulb target the vomeronasal amygdala, which signals to the hypothalamus
o Involved in detection of pheromones (non-volatile substances)
Describe the structure and location of the vomeronasal organ
Vomeronasal organ- bilateral tubular structure in the posterior end and opens into the nasal cavity or the oral cavity
Describe the structure of the accessory olfactory bulb
Accessory olfactory bulb- located posterior and dorsal to main olfactory bulb
Describe the role of the hypothalamus in olfaction
Hypothalamus- has neuroendocrine functions and plays important roles in reproduction
How many odorant receptors does the olfactory system have and how many genes code for these odorant receptors? How many of these genes are pseudogenes?
o Human- about 900 odorant receptors
1000 genes encode for odorant receptors
• Of the genes that are supposed to encode for odorant receptors, 60% are pseudogenes
Why are many olfactory genes in humans pseudogenes?
Largest gene family
Humans don’t have a great olfactory system and have many olfactory pseudogenes because humans rely much more on visual system
• Organisms with trichromatic vision (such as humans) have higher number of olfactory pseudogenes than organisms with dichromatic vision
On which chromosomes are olfactory genes found?
Many genes are found on chromosome 11 and 1
How many olfactory receptors do mice have?
o Mouse- about 1300 to 1500 receptors
What is the identity/ structure of the proteins encoded by olfactory genes? What is the function of these proteins?
• Olfactory genes encode for proteins which are G protein coupled receptors
o Structure
7 transmembrane spanning domains coupled to a G protein (Golf)
• G proteins involved in transduction mechanisms-
o Precambrian ancestry
o G proteins have 3 different subunits-
Alpha subunit
Beta subunit
Gamma subunit
What are the steps in olfactory sensory transduction (starting from an odorant molecule to the olfactory bulb)?
o Odorant molecule binds to specific receptor protein
o Receptor-odorant complex activates Golf
In Golf, alpha subunit will exchange GTP for GDP
o Golf alpha subunit dissociates from beta and gamma subunits and activates adenylyl cyclase (ACIII), which synthesises cAMP using ATP-> this results in increased cAMP concentration
o cAMP activates cyclic nucleotide-gated channel-> allows sodium/calcium ions to enter and depolarise the cell, creating a generator potential
In addition, when calcium enters the cell, calcium can activate a chloride channel that will produce an eflux of chloride ions out of the neuron, making the membrane potential more positive
o Neuron will carry the signal to the olfactory bulb
What is the role of calcium during olfactory transduction?
Adaptation of the receptor system to the continuous presence of odorant
When there is an increase in intracellular calcium concentration, can produce negative feedback on the cyclic gated nucleotide channel that leads to an increase in the Kd for cAMP (sensitivity of the channel to the agonist (cAMP) is reduced)
Calcium produces phosphorylation of adenylyl cyclase (leads to reduction in concentration of cAMP)
Calcium also activates Sodium-Calcium exchanger which leads to repolarisation of the olfactory sensory neuron
o Increased intracellular calcium in response to an odorant leads to a reduced response to the odorant as the system adapts in the continuous presence of the stimulus
Do all olfactory receptors respond to individual/mixed odorants in the same way? Explain
• Different olfactory receptors neurons respond to different single odorant compounds selectively and to different mixtures of odorant compounds selectively
o Some olfactory receptor neurons can respond to odorants in one family but not to others in different families
Compounds which are structurally similar can lead to very different perceptions
How can different mixtures of odorants be integrated by a single olfactory sensory neuron? Explain how each integration can work
Additivity
• Two compounds individually
• As the concentration increases, the response to individual compounds gets stronger
• When two compounds are added together, there is an additive/synergic phenomenon- the responses of individual compounds at a given concentration add together (frequencies of two compounds add together) when they are smelled together
• When two compounds are added together at high concentrations, hypoadditivity can be seen- the response to the mixture is weaker than the sum of the individual responses
Suppression
• When two compounds are applied together at high concentrations, the response to the combination of odorants is weaker than the response to the individual odorants
How many olfactory stimuli can humans potentially discriminate?
• Humans can potentially discriminate more than 1 trillion olfactory stimuli
What inputs to the olfactory bulb and how?
• Input- olfactory sensory neurons
o Axons of bipolar neurons cross the ethmoid bone and synapse onto the dendrites of mitral cells in specialised structures called glomeruli
What neurons output from the olfactory bulb?
• Glomeruli neurons project back to cerebral cortex
o Output- olfactory cortex
Describe the cells in the olfactory bulb structure
o Glomeruli o Mitral cells o Tufted cells o Periglomerular cells o Granule cells
Describe the structure and composition of the glomeruli
Spherical knots (diameter between 50 and 100 um) formed by synapses between olfactory sensory neurons and dendrites of mitral and tufted cells
Which olfactory sensory neurons converge on a singular glomeruli and why do they do so?
• Olfactory sensory neurons expressing the same olfactory receptors project to the same glomeruli (converge)
o If odorant produces very small increase in the activity of individual olfactory sensory neurons, one extra potential is produced (above spontaneous firing rate)
o When these individual sensory neurons converge on mitral cell on olfactory bulb, this mitral cell will have a significant increase in its activity
o The effect of convergence is effectively an increase in the signal to noise ratio that helps discriminate and detect presence of odorant
Describe the impact of receptor dynamic range fractionation and convergence on olfactory receptors and mitral cells
• Dynamic range fractionation
o Olfactory system is sensitive across broad range of concentrations
o Individual receptors need to have very steep curve because want to encode with changes in action potentials small differences in concentration
o Olfactory sensory neurons converging on individual glomeruli have different activation points
Some are sensitive to very low concentrations, others to intermediate concentrations, others sensitive to high concentrations
o When these olfactory sensory neurons converge onto mitral cell, they confer mitral cell with sensitivity to much broader range of concentration
What is the purpose of lateral inhibition in the olfactory bulb and by what cells is it conducted?
Lateral inhibition in olfactory bulb
• Contrast enhancement
• Lateral inhibition by periglomerular cells
• Tuning and integration of odour representation
What is the role of the mitral cells in the olfactory bulb?
Main output cells of the olfactory bulb: output forms lateral olfactory tract (LOT)
What is the role of the tufted cells in the olfactory bulb?
Output cells
Superficially located
Some do not project via lateral olfactory tract
What is the role of the periglomerular cells in the olfactory bulb and what are they?
Small bodies
Interneurons
Lateral processes contact mitral cell and tufted cell dendrites, extending up to 5 glomeruli away
Involved in lateral inhibitory action
What is the role of the granule cells in the olfactory bulb?
Inhibitory interneurons
Receive input in glomeruli from bipolar cells
What is the role of the pinhole aperture in the eye?
o Pinhole aperture
Controls how much light goes into the eye
What is the role of the lens in the eye?
o Lenses- focus light at level of retina
Refraction-bending of light ray
Accommodation-compensating for the distance of objects
What is refraction of light and what law does it follow?
Refraction- bending of light waves towards the normal of the boundary of the two media when they pass from one medium to another where it propagates at a different speed
Snell’s law: n_1/n_2 =〖sinϕ〗_2/(sinϕ_1 ) where n=c/v
What is the difference between convex lens and concave lens?
Convex lens- centre is thicker than the edges
Concave lens- centre is thinner than the edges
When a ray of light hits a convex lens, does it converge or diverge?
Converge
When a ray of light hits a concave lens, does it converge or diverge?
Diverge
Describe how distance of a light ray from a convex lens affects how light will hit the lens and the focal point
When light is coming from a distant source, light will reach the lens in parallel manner and they will be focused at a close focal point
When light is coming from a closer source, light will reach the lens in a divergent manner and will be focused at a distant focal point
How is the image formed by light always formed at the level of retina if the distance between the cornea and light source is variable?
• Distance between the cornea and eye is fixed so image in visual system has to be formed at level of the retina
• As receive light from many different distances, need different lens strengths
o If light coming from near source, need to use stronger/thicker lens
Describe the structure of the eye (including all its layers)
o Outer layer: Sclera- o Middle layer: Choroid o Interior part- Retina • Anterior layer- o Outer layer: Cornea o Middle layer: Iris
What is emetropia?
Normal vision
How does emetropic vision deal with a light source that is far away?
o Light coming from far source-
Focusing power of cornea will bring light rays at level of retina
How does emetropic vision deal with a light source that is close to the eye (less than 6 metres)
Accommodation occurs-
• Activation of neural cell that leads to level of contraction of some muscles that are linked to lens by suspensory ligaments
• Suspensory ligaments become slacker, and elastic lens changes its shape and becomes broader- changes lens power
• Brings image to closer focal point until image is sharp at level of retina
How many diopters does the human visual system have and how are they allocated?
In human visual system, have approximately 60-65 diopters
• Most of focusing power (42 dioptres) comes from the cornea
• 20 dioptres come from second lens
What are diopters?
unit of focusing power
Does accommodation power in the visual system increase or decrease with age?
Accommodation power decreases with age
• This is because second lens keeps growing as human ages-> more accumulation of epithelial tissue added to lens
• Lens becomes more rigid-> loses elasticity-> loses power of accommodation
What is the structure and role of the sclera in the eye?
Tough membrane of connective tissue
Provides structure and entourage for eye masses that move the eye
What is the role of the choroid in the eye?
Rich plexus of capillaries that provide nutrient and oxygen to retina
What is the role of the retina in the eye?
Where light is focused (especially on fovea)
What is the structure and role of the cornea in the eye?
Transparent part of the eye
Most powerful lens of the eye
Focuses light
• Second lens crystallin very important when focus on nearby objects
What is the role of the iris in the eye?
Structure that forms the pupil and provides aperture for light to go through the eye
What is myopia and when does it occur?
Nearsightedness
o Occurs when eyeball is too elongated
What is the problem of myopia and how is it corrected?
Light comes from far source
• Cornea will form an image in front of retina (blurred image)
o Corrected with concave lens
What is hyperopia and when does it occur?
• Hyperopia (farsightedness)
o Occurs when eyeball is too short
What is the problem of hyperopia and how is it corrected?
Light comes from near source
• Light travels too far and is not focused at level of retina
o Corrected with convex lens
What is the optic disc?
• Optic disc- area where axons of ganglion cells bundle together, veins and arteries and exit the retina, forming the optic nerve
What is the fovea?
• Fovea- area where light is focused and it provides us with high visual acuity
What is the retina, what are its dimensions and what does it do?
o Part of the brain
o Thin layer of nervous tissue
o Diameter- 32 mm
o Thickness- 0.2mm thick
o Converts an optical image into electrical signals
o Compares intensity levels
o First step of image processing
o Parallel processing of visual features by different channels
Specialised channels to cover information about different visual features (colour, contrast, light intensity…)
Describe what happens when light hits the retina and how the signal is sent from the retina to the rest of the visual system
- When light hits the retina, light has to go through several layers of nerve cells before being absorbed by photoreceptors in outer segments
- Photoreceptors send signals back to ganglion cells for transfer
What are the 6 retinal layers?Describe them
o Photoreceptors- inner and outer segments Where phototransduction takes place o Outer nuclear layer 3 nuclear layers Where cell bodies of rods and cone photoreceptors are found o Outer plexiform layer Where photoreceptors synapse o Inner nuclear layer Bipolar cell bodies Horizontal bodies Amacrine bodies o Inner plexiform layer All the information processing takes place (synapses from bipolar, horizontal and amacrine cells between themselves) o Ganglion cell layer Output of the retina Where bipolar cells and amacrine cells synapse on ganglion cell layers
What are the two types of photoreceptors?
- Rods
- Cones
What is the structure of rods and the purpose of rods?
• Low light vision (nightime)
o Elongated outer segment with membranous discs containing rhodopsin protein (important for phototransduction process)
What is the structure of rhodopsin?
Rhodopsin has two different parts
• Membrane protein synthesised by golgi apparatus of photoreceptor
• Vitamin A derivative called retinal which is provided by pigment epithelium -provides rhodopsin molecule with light sensitivity
Rhodopsin has seven transmembrane spanning domains
How does phototransduction occur within rods? Describe what happens when the photoreceptor is in the dark vs when it is in the light
In the dark, photoreceptor contains high concentration of cGMP and contains rhodopsin’s retinal in its 11-cis configuration with its bent tail
• At high concentrations, cGMP activates a cyclic nucleotide gated channel that keeps a constant influx of sodium and calcium that keep the membrane depolarised
• When photoreceptor is depolarised, it releases glutamate
When light hits the rhodopsin’s retinal protein (photoisomerization), it will undergo conformation change in which the tail gets straightened and transforms into all-trans retinal- makes meta-rhodopsin configuration
Meta-rhodopsin will stimulate a membrane protein called transducin (G protein), where the alpha subunit of the G protein will exchange GTP for GDP and break away from its beta and gamma subunits
Transducin alpha subunit will stimulate phosphodiesterase and produce a conformational change in its structure and expose its catalytic sites
Phosphodiesterase will break down cGMP, forming GMP from cyclic GMP, which opens a membrane channel
When this happens, there is reduction in concentration of cGMP-> leads to closure of cyclic nucleotide gated channel and hyperpolarisation of photoreceptor (as potassium still leaving the cell) -> less release of glutamate
• Stimulation of light= hyperpolarisation
Change in the amount of transmitter being released is signal that photoreceptor passes on to postsynaptic cells (bipolar and horizontal cells)
What is the structure and purpose of cones?
• Daytime/high light intensity vision- cones
o Types of photoreceptors have different pigments
o S cone
o M cone
o L cone
o Conical outer segments
What are the two different retinal cell layer pathways?
o Vertical pathways
o Horizontal pathways
Describe the vertical pathway in terms of:
- Pathway
- Transmitter used
- When it is activated
Involves photoreceptor->bipolar-> ganglion cell-> brain areas
Transmitter used= glutamate
When light stimulates centre of receptive field of ganglion cell
Describe the horizontal pathway in terms of:
- Pathway
- Transmitter used
- When it is activated
Involves horizontal and amacrine cells-lateral inhibition
Transmitter used= GABA and glycine -inhibitory signals
When light activates periphery of ganglion cell, due to increased intensity in periphery rather than centre, will inhibit signal
How many types of bipolar cells are in the primary retina?
• 15 types of bipolar cells which have different cell morphology, different axon termination in different stria in inner plexiform layers and different cell body locations o Cone bipolars 14 types of bipolar cells Contact cone photoreceptors o Rod bipolar cell Only one type Contact rod photoreceptors
Where are the bipolar cell axon terminals found in the inner plexiform layer?
• Bipolar cells have axon terminals in either off-sublamina stria in the inner plexiform layers or on-sublamina stria in the inner plexiform layers
o Bipolar cells stratifying in different areas have different properties-respond to light with different signalling mechanisms
What ganglion cells do off-sublamina stria bipolar cells send signals to? What do they respond to?
Off bipolar cells pass signals to off-ganglion cells
• Respond with an increase in their activity when there is a reduction in light intensity
What ganglion cells do on-sublamina stria bipolar cells send signals to? What do they respond to?
On bipolar cells pass signals to on-ganglion cells
• Respond to light with an increase in their activity when light is turned on- signal increase in light intensity
What are some examples of ganglion cells?
• Some types of ganglion cells that differ in their morphology and function include:
o Local contrast detectors
o Direction selective neurons
o Local edge detectors and orientation detectors
o Fast motion detector
o Luminosity detectors (tonic units)
How is visual information processed in the retina?
• Every single point in the retina hit by a light source is covered by every different physiological type of ganglion cell. Thus, each point is simultaneously analysed with regards to its contrast, colour, movement, as well as other characteristics.
o Information not segregated 100%- some crossover between channels
o However, one channel most likely to look at one feature of visual field (colour, movement…)
o Binding puts all separate features of visual field together
• Parallel processing of visual information starts in the retina
What photoreceptors mediate the photopic vision circuit?
Photopic vision- daylight cone circuit
• Mediated by cone photoreceptors
Describe the general outline of the phototopic vision circuit (focus on components rather than mechanisms)
• Cones respond to light through hyperpolarisation
• Contact two different types of bipolar cells
-On cone bipolar cell
• When photoreceptor hyperpolarises and releases less glutamate, the response of the on bipolar cell is a depolarisation (sign inversion of the signal)
o In response to light onset, on bipolar cell depolarises
Bipolar cells do not generate action potentials, but have graded responses
When on bipolar cell depolarises, it releases glutamate on on ganglion cell
• On ganglion cell is capable of producing action potentials
-Off cone bipolar cell
• Hyperpolarisation of photoreceptor produces hyperpolarisation of off bipolar cell
o Sign conservation of the signal
When there is illumination, the off bipolar cell will fire less/no action potentials-> off ganglion cells produce no action potentials
o Off cone bipolar cell
Describe the synapse between the on cone bipolar cell and the cone photoreceptor in the photopic vision pathway. Include:
- Morphology of synapse
- Receptor in synapse
Synapse between cone photoreceptor and on cone bipolar cell
• Forms invaginating synapse
• Dendritic tip of on bipolar cell enters omega-shaped indent in photoreceptor
• Dendritic tip is postsynaptic to specialised structure which is the electrodense part of the terminal to which synaptic vesicles are tethered
• Dendritic tip of the bipolar cell expresses specific type of glutamate receptor which is a metabotropic glutamate receptor (mGluR6)
What is a metabotropic receptor and how does it work?
o Metabotropic- G protein coupled receptors
7 transmembrane spanning domains
Coupled to G protein and secondary messenger cascades which will then act on membrane channel
What is an ionotropic receptor and how does it work?
o Ionotropic receptors
Receptors that contain a pore within their structure
When it is activated, will undergo conformational change, and there will be a pore/channel that opens within the structure-> allows movement of ions
Describe how the photopic pathway’s mGluR6 functions in the dark in comparison to in the light
In the dark:
• There is a very high concentration of glutamate in the synaptic cleft
• Glutamate activates the mGluR6
• When mGluR6 is activated, the sodium calcium membrane channel is closed
In the light:
• When reduction in amount of glutamate due to phototransduction, then glutamate receptor will not be activated anymore
• G protein will separate from receptor,
• The sodium calcium membrane channel opens
• Allows influx of positive ions which depolarises the bipolar cell
What happens when mGluR6 is activated vs when it is not?
o Activation of mGluR6 keeps membrane hyperpolarised
o When mGluR6 is not activated, membrane is depolarised
What is the target of the mGluR6 signal transduction pathway in the photopic pathway? What happens if that target goes mssing?
o TRPM1 is the target of the mGluR6 signal transduction cascade
High density of TRPM1 channels in the outer plexiform layer (where photoreceptors make contact with bipolar cells)
Without TRMP1 channels, no activity in on bipolar cells
What are the two channels involved in photopic vision? What is the purpose of each one?
On channel- channel that increases its activity with increases in light intensity. Involves the on bipolar cells
Off channel- optimised to transmit illumination about decreases in light intensity. Involves the off bipolar cells
• Increases in light intensity suppress activity in off pathway
• Decreases in light intensity increase activity in on pathway
Describe the synaptic contact between photoreceptors and off bipolar cells in terms of:
- Morphology
- Receptors
• Dendritic peaks of on bipolar cells make flat contacts with photoreceptors
• Off bipolar cells express ionotropic glutamate receptors
o AMPA/KA receptors
o Receptors open in the presence of glutamate
Describe how the photopic pathway’s ionotropic receptors functions in the dark in comparison to in the light
• Process
o Glutamate in the cleft is high in the dark-> will keep ionotropic receptor open
o When there is reduction of glutamate due to illumination, then the ionotropic receptor will close and the off bipolar cell will hyperpolarise
What photoreceptor controls the scotopic vision pathway?
Scotopic vision (nighlight)- conventional rod pathway
Relative to the photopic pathway, when did the scotopic vision pathway develop? How does this impact the structure of the scotopic pathway?
• Rod pathway appeared later in evolution than cone pathway
• Only one type of rod bipolar cell that contacts the rods
o Not possible to split on and off pathways
• Uses pre-existing on and off cone bipolar cells by using amacrine cell (AII) that it uses to transfer the rod signals onto the cone pathway
Describe the structure of the amacrine cell and the location of these structures
o Amacrine cells- most of them do not have axons, only dendrites
There are two important dendritic areas
• Outermost part of inner plexiform layer (off sublaminar)
o Lobular appendages
Relatively thick dendrites with globules
• Innermost part of inner plexiform layer
o Arboreal dendrites
Plexus of Thin and long dendrites
Describe the scotopic pathway when light is shone on the rods
• Light responses in rod pathway
o Rods response to light by hyperpolarising
At the synaptic contact between rods and bipolar cells, there are mGluR6 receptors that invert the sign of the signal
o Rod bipolar cells (on bipolar cells) depolarise
Glutamatergic cell
o AII amacrine cell, when there is increase in light intensity, will depolarise
AII amacrine cell expresses ionotropic receptors- there is a sign conservation from the rod bipolar cell
o Off cone bipolar cell hyperpolarises whilst the on cone bipolar cell depolarises
AII amacrine cell forms gap junction synapses with on cone bipolar cell with arboreal dendrites-> when AII amacrine cell depolarises, the sign is conserved
AII amacrine cell makes glycinergic synapses with off cone bipolar cell with its lobular appendages-> will release glycine on terminal of off cone bipolar cell-> off cone bipolar cell will hyperpolarise
• Glycine is inhibitory transmitter
o Off ganglion cell will reduce its activity and the on ganglion cell will increase its activity
In the scotopic pathway, where does the splitting of signals into the on and off channels occur?
• The splitting of signals into the on and off channels is at the level of inner plexiform layer
Describe different photoreceptors distribution ratio to ganglion distribution ratio
o 126 million photoreceptors-> about 2 million ganglion cells
120 million rods- 120 rods to one ganglion cells
6 million cones- 6 cones to one ganglion cell
What is the receptive field of the ganglion cell?
• Receptive field of ganglion cell- the area of the retina that, upon illumination, will produce change in the firing rate of the ganglion cell
What are the two areas in the receptive field of a ganglion cell and what happens when there is illumination in these areas
o Two areas
Excitatory centre
• Illumination of this area produces an increase in firing rate
Inhibitory surround
• Illumination of this area produces a reduction in firing rate
o Does this through lateral inhibition, which enhances contrast
What determines the overall output of a retinal ganglion cell
o Overall output of ganglion cell is the balance between light stimulation of the excitatory centre and the light stimulation of the inhibitory surround
Describe what happens when there is illumination in the centre of the retinal ganglion cell
Centre illumination-
• Stimulation of photoreceptors will produce depolarisation of the bipolar cell
• Bipolar cell will release more glutamate on ganglion cell-> will be increase in firing rate
Describe what happens when there is illumination in the surrounding of the retinal ganglion cell
Surrounding illumination
• There will be horizontal cells, bipolar cells and amacrine cells that receive input from photoreceptors
o Horizontal cells and amacrine cells contain inhibitors
• These cells will connect horizontally to centre pathway
• Therefore, when periphery is illuminated and centre is dark, the amacrine and horizontal cells will be stimulated and they will connect laterally to inhibit transmission along central pathway
• That will result in reduction of transmission of information from the on ganglion cell
Describe the location and neurotransmitter of horizontal cells
Horizontal cells- GABA- in outer plexiform layer
Describe the location and neurotransmitters of the amacrine cells- where are their synapses located?
Amacrine cells- GABA or glycine – in inner plexiform layer
• Inhibition occurs at multiple sites
o Synapses between amacrine cell and dendrites of bipolar cell
o Synapses between amacrine cell and dendrites of ganglion cell
What is the role of direction selective ganglion neurons and what type of ganglion cell receptive field is it made from?
o Neurons that respond to movement in one direction (preferred direction) but not in opposite direction (null direction)
o ON-OFF receptive field centre ganglion cells
Respond to onset and offset
How do direction selective ganglion neurons work?
Direction selectivity results from excitatory and inhibitory conductance preference for opposite directions
• When the stimulus moves in preferred direction, excitation precedes inhibition and excitation is slightly larger than inhibition
• When the stimulus moves in the null direction, inhibition occurs before excitation and is larger than excitation
By different arrangements of the synapses, this computation is achieved, and this computation consists of a difference in magnitude and time of arrival of excitation and inhibition
• If excitation precedes inhibition, cell will depolarise and fire action potentials
• If inhibition precedes excitation, cell will be hyperpolarised
o Most complex information processing task performed by vertebrate retinas
o Responses independent of the nature of the object (bright or dark; small spot or drifting grating)
Describe the role of intrinsically photosensitive ganglion cells, their components, their roles and outputs
• Intrinsically photosensitive ganglion cells (ipGC)
o Respond to light stimulation independently of rod and cone input
o Contain photosensitive pigment melanopsin and project to suprachiasmatic nucleus and olivary pretectal nucleus
o Mediate photoentrainment (circadian rhythms and pupillary reflex)
