OPTO30007 Notes SM2 2024 PDF

OPTO30007 – NOTES SM2 2024 LECTURE 1 – WEEK 1 – ANATOMY OF THE EYE Problem 1: - 47yo lady experiences deep boring pain in the left eye whilst watching movie - Sees haloes - (Vision below 6/12 are not suitable for driving), the lady has a vision of 6/6 in the left eye Examination = narrow anterior chamber angle (a shallowing of drainage angle in the front part or anterior chamber of the eye) this menas that the angle between the iris and the cornea is narrow…. what does this mean for the lady? The symptoms and findings described in the scenario suggest that the 47-year-old lady may be experiencing an acute angle-closure glaucoma attack. Here’s what each finding typically indicates: 1. Deep boring pain in the left eye: This is a common symptom of acute angle-closure glaucoma. It occurs due to increased pressure inside the eye (intraocular pressure) which can lead to damage of the optic nerve. 2. Sees haloes: Haloes around lights are another classic symptom of acute angle-closure glaucoma. These haloes are caused by corneal oedema (swelling), which occurs due to the increased pressure in the eye. 3. Vision of 6/6 in the left eye: This means her visual acuity in the left eye is normal (6/6 is equivalent to 20/20 in Snellen notation). However, despite good vision, the other symptoms are concerning. 4. Examination finding of narrow anterior chamber angle: This is a critical finding. It suggests that the angle between the iris (colored part of the eye) and the cornea (clear front part of the eye) is narrow. In acute angle-closure glaucoma, this angle becomes even narrower or closes completely, leading to a sudden rise in intraocular pressure. What does this mean for the lady? Given these findings, the narrow anterior chamber angle indicates that the lady is at risk of developing or may already have acute angle-closure glaucoma. Acute angle-closure glaucoma is an emergency condition that requires immediate treatment to lower intraocular pressure and prevent permanent vision loss. If left untreated, acute angle-closure glaucoma can rapidly lead to irreversible damage of the optic nerve and severe vision loss. Therefore, the lady should be urgently referred to an ophthalmologist for further evaluation and management. Treatment typically involves medications to lower intraocular pressure and sometimes laser or surgical procedures to alleviate the angle closure. (EYE) Outer coat n Cornea and sclera - FUNCTION; Transparency & Strength Middle coat n Ciliary body, iris, choroid - FUNCTION; 1. Aqueous humour production, 2., Accommodation (focusing) 1. Aqueous humour production Important for the health of the Lense and cornea Creates intraocular pressure Formed by ciliary epithelial cells 2. Accommodation (focusing) Ligaments attach to ciliary processes Involves contraction of the ciliary muscle Inner Coat n Retina Optic nerve / optic disk Fovea Macula (are in which the fovea sits) Posterior pole Ora serrata HOW DO WE SEE? ð There are factors that can limit visual acuity, being neural factors and optical factors. (1) Neural factors (2) Optical factors Pupil size Clarity of optical media (cataracts, corneal opacities etc.) Refractive errors (blur) – due to; myopia, hypermetropia, astigmatism, presbyopia. In terms of optical factors, there are multiple which impact vision in general: (a) Cornea / tears: - Emmetropia – where the refractive state of an eye in which paralleled rays of light entering the eye are focused on the retina EXACTLY, creating a crisp image perceived in focus. (b) Axial length of the eye determines power (axial length is the length of the eye from the front to the back) - Myopia – short sightedness, where objects close look clear but far out are blurry - eye growth determines refractive state Myopia, although for short sightedness, is formed with a oblong (long) eye shape. - Hypermetropia – long sightedness, where objects far away look clear but up-close look burry. - Hypermetropia, although for long distance, s formed with a smaller circle eye (opposite of oblong). (c) Variable focus due to crystalline lens: - Balloon suspended in donut (ciliary) muscle - Thickens with age and less plastic - Presbyopia is loss of near focusing ability, at ages 40-45 – need reading glasses. PATHWAY for light: Through: PRCs > BCs > GCs Lateral interactions: 1. Horizontal cells 2. Amacrine cells n RODS: Night vision, ‘scotopic’, very sensitive, one type, no colour vision, 100 million of them, are absent from the fovea n CONES: Day vision, ‘photopic’, less sensitive, three types, allow for colour vision, 5 million of them, -THE NEURAL RETINA- densest in the fovea. => Contains 6 neurons: 1. HCs 2. BCs 3. ACs 4. GCs 5. Rods 6. Cones THE NEURONAL LAYERS OF THE EYE - There are 3 diaerent neuronal layers 1. Outer nuclear layer (ONL) 2. Inner nuclear layer (INL) 3. Ganglion cell layer (GCL) In the INL (inner nuclear layer) Ø Contains the cell bodies of horizontal, bipolar and amacrine cells Ø Contains Müller cells BIPOLAR CELLS in INL: - Important in ‘through’ pathway - 10 diaerent types of bipolar cells - 1 x rod bipolar cells - 9 x cone bipolar cells - Important for spatial vision and colour vision Lateral inhibition INL: HORIZONTAL CELLS - Input from photoreceptors - Provide output onto photoreceptors - Release inhibitory neurotransmitter GABA - Respond to light by hyperpolarizing AMACRINE CELLS in INL: - Many diaerent types - Have no axons (axon less) - Important in lateral inhibition like horizontal cells - Release inhibitory neurotransmitters like glycine & GABA, often co- express more than one neurotransmitter. GANGLION CELL LAYER (GCL) - Cell bodies of GCs and some displaced amacrine cells live in the ganglion cell layer - Ganglion cells are the main output neuron of the retina (many diaerent types: ON, OFF, M & P) - RGCs release Rtamate - RGCs ﬁre action potentials OPTIMIZING VISION: Retinal Structure Macula n Deﬁned by where pigment lies in the retina (where the fovea is), but retinal layers are ‘pushed’ to the side n 3mm diameter n Exists no cells or processes to impede light transfer. The central avascular zone is the optimized vision zone. OPTIC NERVE ð Formed by axons of ganglion cells as they exit the retina to pass visual information to higher cortical areas Note: Lamina cribosa is the area in which the ganglion axons begin to descend into one thick optical nerve, coming from the retina: THE VISUAL PATHWAY BEYOND TRHE RETINA 1. RGCs go to lateral geniculate nucleus (LGN – in thalamus) 2. 55% GC ﬁbres cross at the optic chiasm 3. Cortical cells need stimulation from both eyes to develop properly. If not, amblyopia can form (reduced vision in one eye caused by abnormal visual development early in life) caused from… in diaerence in refractive state, turned eye (squint), congenital cataract or from lid pathology abnormality Glaucoma - A name for a group of eye diseases where vision is lost due to damage to the optic nerve, typically irreversible vision loss. - Types: 1. Angle closure, 2. Angle open - Treatment: preventing RGC loss SUMMARY OF LECTURE: 1. Retina contains 3 neuronal layers (ONL, INL, GCL) 2. Retina contains 2 synaptic layers (OPL & IPL – outer plexiform layer and inner plexiform layer) 3. OPL consists of connections among PRCs, BCs and HCs 4. IPL consists of connections among BCs, ACs and GCs. 5. For vision at high light levels: - Visual acuity is highest at the fovea - Depends on density of cones - Avascular fovea LECTURE 2 – WEEK 1 – THE RETINA 2: PHOTORECEPTORS Lecture concept: What happened when light hits the retina? Problem 1: - 45-year-old lady - Has trouble seeing at night - Trips over her children’s toys - Has had many car accidents over the last 2 years - Can read OK In a photo taken of Joan’s fundus (fundus – is the inside, back surface of the eye), it shows many black spots that hinder the fundus’ natural colouration. What does this mean for the lady?... STRUCTURED OF PHOTORECEPTORS 1. Outer segment – (tip of the actual rod or cone (the shape)) where photopigment us housed 2. Inner segment (main body with nucleus and axon)– where mitochondria and golgi is housed 3. Synaptic terminal – (axon and synaptic terminal) where neurotransmitters are released and where the rod/cone connects via synapse to the bipolar and horizontal cells. THE RELATIONSHIP BETWEEN OUTER SEGMENT DISCS AND RHODOPSIN/OPSINS n Both rod and cone cells utilize their outer segment discs to house light-sensitive molecules – rhodopsin in rods and many diaerent types of opsins in cones. n RODS: the tip (actual rod part) of the rod is known as the outer segment, and it is where rhodopsin molecules are housed, molecules which are photopigments. It consists of a protein called an opsin, bound with a light-sensitive molecule called 11-cis retinal. ð When light enters eye and reaches the retina, it is absorbed by the rhodopsin molecules, triggering a biochemical cascade that leads to changes in membrane potential and ultimately to the generation of neural signals. n CONES: the actual cone tip of the cone is where opsins are housed, which can vary unlike rhodopsin, to diaerent types like red, green and blue cones. – opsin proteins are sensitive to diaerent wavelengths of light ð DiAerent cones respond to diAerent types of wavelengths of light due to the presence of diAerent opsins in their outer segment discs. How do photo receptors respond to light? ð Photoreceptors are hyperpolarized by light. ð Respond to light with graded changes in membrane potential (not action potentials) PHOTOTRANSDUCTION Phototransduction = The process of converting light into electrical signals in photoreceptor cells of the retina. 1. Activation of rhodopsin (opsins in cones) ð Light absorbed by rhodopsin, absorption causes structural change (conformation) in the bound retinal (11-cis retinal converts to all-trans retinal), leading to a conformational change in rhodopsin. 2. G-protein (Transducin) ð Conformationally changed rhodopsin allows for binding and activation of transducing, a G-protein consisting of subunits (a, B, and y). 3. Activation of phosphodiesterase ð Once transducin is activated, GMP bound to the a- subunit is exchanged for GTP (guanosine triphosphate). The now activated GTP subunit binds to and activates an enzyme called phosphodiesterase (PDE) located in photoreceptor outer segment. PDE is normally inhibited in the dark by high levels of [c]GMP. 4. Hydrolysis of cGMP and closure of cGMP gates channels for ion inﬂux. ð Activation of PDE results in hydrolysis (breaking down) of cGMP into 5’-GMP. Decreased levels of cGMP lead to the closure of the cGMP guarded sodium channels responsible for the cells’ depolarisation/hyperpolarisation. ð This in turn reduced the inﬂux of both Na+ & Ca2+ (calcium) into cell, leading to hyperpolarisation in the light. HOW DO PHOTORECEPTORS RECOVER ð This reduces glutamate release from photoreceptor cell onto bipolar cells, FROM LIGHT? which initiated the transmission of the visual signal to the retina and (1) cGMP Control subsequently to the brain. n cGMP controls the ion channels n cGMP is continuously produced by guancylate cyclase (dependent on calcium levels) (2) Restoration of rhodopsin n Activated rhodopsin is rapidly phosphorylated by rhodopsin kinase n This allows binding of arrestin to phosphorylated rhodopsin. n Bound arrestin prevents activated rhodopsin binding to transducin Importance of Calcium in RESTORATION OF THE cGMP activity SIGNAL: CALCIUM In DARK: DECREASED Ca: Ø Calcium passing into - Results In the increase in photoreceptors guanylate cyclase, which makes Via cGMP gated channels cGMP VDCC - Results in increase in rhodopsin kinase, which allows for more In LIGHT: arrestin to bind. Ø cGMP gates channels close - Results in increase in a\inity of Ø reduces Ca inﬂow cGMP for channels. Ø with hyperpolarisation VDCC also - Arrestin produced prevents close activated rhodopsin from binding ð This means that calcium levels to transducin. RESTORATION OF in the cell Is very 11-CIS low. RESPOSNE OF OPSINS TO RETINAL DIFFERENT WAVELENGTHS 11-cis retinal has been decreased as light impacts 11-cis retinal, changing the ð SHORT (S pigment) [Rhodopsin]: conformation of rhodopsin. In doing so, Blue (435 nm) removing the 11-cis retinal which is a ð MEDIUM (M pigment): Green (535 protein attached to rhodopsin. nm) RETINITIS PIGMENTOSA Ø Genetic disorder Ø Creates tunnel vision Ø Is formed by a genetic defect in rhodopsin or proteins involved in phototransduction Ø Is characterised by degeneration of the retina Ø Degeneration of photoreceptor cells (rods and cones) leading to vision loss over time Ø Please explain Retinitis pigmentosa, and talk about its genetic defect in rhodopsin/proteins involved in phototransduction. Talk about how it creates tunnel vision. Thanks LECTURE 3 – WEEK 2 – THE RETINA 3: PARALLEL PATHWAYS Lecture concept: How is information from photoreceptors carried to downstream neurons? Problem 1: Monica Woman aged 65 Noticed a disturbance in her vision Water splashing in front of her left eye ‘Flickering lights’ Trips over her grandchildren’s toys Husband concerned about her driving n Vision 6/9, 6/12 n Good health Grade 3 Melanoma exercised 4 years ago {Lymph nodes +ve} Why is this lady having trouble seeing? LUCA’s Attempt at Answer (not confirmed as right answer): The most logical reason for vision trouble for Monica is potentially due to a Posterior Vitreous Detachment (PVD), an issue common in induvial over 50 where the vitreous gel in the eye detached from the retina. This is because over time the vitreous can shrink and become more liquid, eventually detaching from the retina. Floaters, ﬂashes of light, and visual disturbances are all symptoms of Monica’s that align with the symptoms associated with PVD: Floaters: - Described as ‘water splashing’ in front of the eye, ﬂoaters are small, shadowy shapes that appear in the ﬁeld of vision. They are caused by the vitreous get detaching from the retina, creating shadows on the retina from tiny clumps or strands of vitreous gel/humor. Flashes of light: - Referred to as ‘ﬂickering lights’, ﬂashes of light can occur when the vitreous gel tugs on the retina during detachment, the mechanical stimulation is perceived as ﬂashes of light. Visual Disturbances: - Di\iculty in seeing can lead to tripping over objects or concerns about driving, which is common as the ﬂoaters and ﬂashes PROCESSING can obscure VISUAL vision. INFORMATION Diagnosis: - 6/9 & 6/12 vision indicated a slight to moderate visual impairment, which is consistent with symptoms of PVD, Monica should seek further medical assistance to determine whether her retina is detached or not. (BIPOLAR CELLS) ð 2 di\erent types of bipolar cells exist: ð Both of which are meant to transmit signals from photoreceptors to ganglion cells ð IT IS IMPORTANT TO REMEMBER THAT THE PRESENCE OF LIGHT & GLUTAMATE ON OFF/ON BCs PRODUCE DIFFERENT OUTCOMES, WHERE GLUTAMATE PRESNECE CAN BE HYPERPOLARISING OR DFEPOLARISING DEPENDANT ON LIGHT PRESENCE. (1) On bipolar cells – cells depolarized by light falling on the retina (excited in day, inhibited in night) Are activated when light increases In darkness, continuously release neurotransmitter glutamate which inhibits ON BCs. When light hits ON BCs they hyperpolarize and reduce glutamate release, allowing the bipolar cell to depolarize. RECEPTOR: Have metabotropic glutamate receptors (mGluR6 – associated with TRPM1 channels), that when bound to glutamate, activate a cascade that keeps the cell hyperpolarised, when glutamate levels drop due to light, the cell depolarizes. > ON BCs hyperpolarise with increased glutamate. Less TRPM1 channels may lead to inability to e\ectively process visual signals in dim lighting. HOW DOES GLUTAMATE CAUSE HYPERPOLARISATION of ON BCS? - When light is present, this decreases the level of glutamate release, therefore mGluR6 activation is decreased with less available glutamate to bind to them. The downstream process of this lowers the IP3 & DAG levels, ultimately closing the TRPM1 channels. - Without the inﬂux of Na+ and Ca+ ions, the ON-BC become hyperpolarised. TRPM1 Channels Ø Appaloosa horses have reduced mRNA TRPM1 and have reduced b-wave and night blindness. Ø The b-wave of the electroretinogram (ERG) reﬂects activity of ON-BCs. Ø In Appaloosa horses with reduced TRPM1 channels, results in a weaker b-wave response in the ERG. Ø Nyctalopia (night blindness) – di\iculty seeing at night, occurs because the ON- BCs are not able to respond properly to reduced levels of glutamate during low- light condition. Less TRPM1 channels may lead to inability to e\ectively process visual signals in dim lighting. (2) OW bipolar cells – cells hyperpolarized by light falling on the retina (inhibited in day, activated in night) Depolarise when light decreases, cells are excited by glutamate. In darkness, photoreceptors release glutamate continuously like ON BCs, which excite & depolarize the cell. When light is on retina, glutamate release reduces and hyperpolarises OFF bipolar cells RECEPTOR: Have ionotropic glutamate receptors (AMPA, NMDA & Kainate receptors), that open in response to glutamate allowing for depolarisation of cells (by allowing +ve ions to enter cell) > OFF BCs depolarise with increased glutamate. GANGLION CELLS Ø Output neurons of the retina Ø Many di2erent types of cells (M ganglion cells & P ganglion cells), they both encode di2erent types of visual information Magnocellular GCs n Magni – large n Large receptor ﬁelds n Subserve motion detection, ﬂicker and analysis of gross features (quick recognition of and processing of the overall scene or object without focusing on ﬁne details) Ø Handle high frequency changes of light Ø Fast adaptions Parvocellular GCs Parvi = small More numerous Visual acuity and colour vision Ø Handle low frequency changes of light. Ø Slow adaptions ð Bipolar cells synapse with ganglion cells ð Ganglion cells can be ON or OFF types ð ON BCs can only synapse with ON GCs, and the same goes for OFF BC/GC. ð Communication between BC and GCs is done via iGluRs such as NMDA, AMPA, and Kainate receptors. GC Function Kuffler, 1953 ð GCs function by integrating all the information signalled from the photoreceptors, allowing the process of conveying visual information like contrast and spatial details. ð Central and Surround are two separate pathways coming from the photoreceptor to the GC. ON CENTRE FIELD GC: ð These cells are excited when light falls onto the centre of their receptive ﬁeld, and inhibited when light falls on surrounding area OFF CENTRE FIELD GC: (Centre-Surround Organization) ð These cells are excited when light falls onto the surrounding area of their receptive ﬁeld, and inhibited when light falls onto the receptive ﬁled. ð BOTH these cells are important in detecting contrast, allowing them to detect edges and boundaries in the visual scene (important in spatial perception) CENTRAL & SURRUONDING PATHWAYS CENTRAL: n A pathway that provides a direct measure of light in the central part of the receptor ﬁeld, from photoreceptors, to BCs, to GCs. - This pathway contributes to detailed visual processing, the intensity of light and contrast. SURROUNDING: n A pathway that provides indirect pathway that involved horizontal cells that provide lateral inhibition to modulate activity of bipolar cells. The level of inhibition of BCs onto GCs is determined by level of surrounding light present. - This pathway contributes to enhancing contrast and edge detection, improving contrast and spatial resolution. - HCs release GABA *Centre-surround organization enhances our ability to see contrast at borders. WHAT WAS WRONG WITH MONICA? CONFIRMED ANSWER Ø Melanoma Associated Retinopathy Ø Rare complication of melanoma Ø Antibodies are produced directed against ON BCs (autoimmune disease) Ø Patient treated with oral prednisolone Ø There is less function of the ON BCs LECTURE 4 – WEEK 2 – THE RETINA 4: ROLE OF AMACRINE CELLS Lecture concept: What do amacrine cells do? Problem 1: What’s wrong with baby Jane? Jane is a 10-year-old twin At 3mo of age, father noticed horizontal eye movements (quivering eye movements) Examination: bilateral nystagmus Brain imaging all normal Genetic testing: FRMD7 mutation (on X chromosome) Why is this child having trouble seeing? LUCA’s Attempt at Answer (not confirmed as right answer): (UN_ANSWERED) ACTUAL ANSWER BY INVIGILATOR: ð Jane’s bilateral nystagmus (rapid, uncontrolled eye movements) is associated with a mutation in the FRMD7 gene. This gene is critical for proper functioning in of starburst amacrine cells, which are responsible for horizontal motion detection. ð The mutation disrupts these cells, leading to the loss of optokinetic nystagmus and resulting in involuntary horizontal eye movement. This condition known as pendular nystagmus, a\ects about 1 in 1500 people, with 70% of people attributed to FRMD7 mutations. FRMD7 Gene: required for horizontal motion detection. Ø Essential for proper function of horizontal motion detection mechanisms in the retina Ø FRMD7 deﬁciency: Leads to dysfunction in SACs, impairing horizontal motion detection, important in stabilizing gaze and smooth pursuit eye movements. Gene Expression: By Starburst Amacrine Cells Optokinetic Nystagmus (OKN): Eye movement in response to moving stimuli, crucial for tracking objects. - Impact of FRMD7 mutation > Loss of OKN due to impaired SAC function, leading to the inability to stabilize gaze during horizontal motion. TYPES OF AMACRINE CELLS: Ø Roughly 22 types Ø Neurotransmitters used - All contain Gaba or glycine - Some also contain Ach, Dopamine, neuropeptides [Amacrine cell inputs] * Amacrine cells modify bipolar cell response I.e., modify the retinal ‘though’ signal [Amacrine cell functions] Amacrine cells release GABA and glycine onto bipolar cells and ganglion cells, ‘ﬁne tuning’ the ‘through’ response. In terms of the rods and cones, all cone bipolar cells synapse onto ganglion cells, however rod bipolar cells only synapse with amacrine cells. In light, cones signal to bipolar cells, while at low light level the cones are not sensitive enough to signal, and so the rods signal to bipolar cells. Rod bipolar cells receives input from ONLY rods, where they express mGluR6 receptors, and depolarize when light falls on the retina. THE AMACRINE CELL & ROD PATHWAY ð 1 x Rod bipolar cells synapse with two amacrine cells. ð All amacrine cells express iGluRs (i.e will depolarize when RBCs depolarize), where glycine is the neurotransmitter. ROD PATHWAY n RBCs DO NOT synapse with GCs n Rod pathway ‘piggy backs’ onto the cone pathways. n The density of all amacrine cells limit the visual acuity at night (recap: both the OFF BCs and OFF GCs hyperpolarize to light, & ON BCs and ON GCs depolarize to light. OFF BCs hyperpolarize in response to glycine So, because RBCs do not synapse with GCs, they actually synapse with the All Amacrine Cells (AACs). The AACs then send signals received from RBCs, to CBCs. This actually allows the CBC pathways to integrate the RBCs neural signal into the ganglion cells. So yes, the Cone Bipolar Cell does the work for the Rod Bipolar Cell via Amacrine Cells. AMACRINE + GANGLION CELLS – DETECTING MOTION (1) Photoreceptor activation (2) Bipolar cells receive input from photoreceptors and transmit onto amacrine cells. (3) Amacrine cells, part of them includes a class of Starburst Amacrine Cells (SACs or SBACs). Starburst amacrine cells are a specialized type of amacrine SACs/SBACs’ directionally tuned inhibition Ø This mechanism describes the ensuring that SBACs provide inhibitory input to DSGCs only when motion is detected in the null direction, thereby enhancing the direction selectivity of DSGCs, and providing accurate motion detection in the visual system. Ø Calcium responses: SBAC dendrites exhibit varying calcium responses along their length, the signal intensity (amount of calcium released) depends on the direction of the stimulus. Ø GABA release – is the inhibitory neurotransmitter which is released when the stimulus moves form the soma (cell body) outward along the dendrite (in a centrifugal direction), but NOT when it moved toward the soma (centripetal direction). THEREFORE, ð GABAergric inputs onto DSGCs come from SBAC dendrites that are orientated in the null direction. Why Care About Motion Detection? n DSGCs target 3 major pathways/regions of the brain: (1) LGN – Lateral Geniculate Nucleus - Is relay centre in thalamus for visual information from retina to visual cortex - It processes motion signals and contributes to the perception of movement, enabling the brain to interpret dynamic visual scenes (2) Superior Colliculus - Involved in orienting movements of the eyes and head towards stimuli - Helps coordinate rapid eye movements (saccades) to track moving objects, facilitating attention and focus on relevant visual information. (3) Accessory optic nucleus - Involved in stabilizing the visual ﬁeld during head movements - Process motion information to adjust eye movements and maintain stable vision, crucial for navigating the environment. LECTURE 5 – WEEK 2 – THE RETINA 5: ROLE OF GANGLION CELLS Lecture concept: Types of ganglion cells and their roles. TYPES OF GANGLION CELLS (1) PARASOL GANGLION CELLS (M-GCs) Ø Magni = large receptor ﬁelds Ø Allow for motion detection, low light vision, ﬂicker and analysis of gross features Ø Low spatial resolution, but high temporal resolution Ø Not densest in the fovea Ø Where multiple fovea cones synapse with multiple ON or OFF bipolar cells, which synapses with a single ON or OFF M-Ganglion cell. => Because of this, Midget ganglion cells (M-GCs) cannot produce great visual acuity. (2) MIDGET GANGLION CELLS (P-GCs) Ø Parvi = small receptor ﬁelds Ø More numerous in numbers than MGCs Ø Allow for visual acuity and colour vision Ø High spatial resolution, but low temporal resolution Ø Densest in the fovea Ø Where one parafovea cone synapses with one ON or one OFF bipolar cell, which synapses with a single ON or OFF M-Ganglion cell. => Because of this, P-Gcells (P-GCs) can produce great visual acuity. = The Midget System (3)INTRINSICALLY PHOTOSENSITIVE GCs Ø Bistratiﬁed Ø Small Ø Spare (very few) Ø Very important in the non-vision encoding aspects of light detection (tell our body when the lights are on) This speciﬁc class of GCs are in their own way, photosensitive just like COLOUR DISCRIMINATION photoreceptors. ð Within the eye, there are more red cones, then green cones, then blue cones There are: 1. Blue cones: respond well to wavelengths 430 2. Green cone: respond well to wavelengths 530 3. Red cones: respond well to wavelengths 560 Colour Comparisons by RGCs (retinal ganglion cells) n Midget ganglion cells exhibit a colour opponent centre-surround surface, with the bullseye being the best reaction for ON GCs, and the surrounding area around the bullseye being the best place for reaction for the OFFS GCs. n Some midget ganglion cells are excited by red falling on their centre and inhibited by green falling the surround (peripheral). n Others are excited by blue or yellow lights falling on their receptor ﬁeld centre. n Colour perceived is determined by the activity of ganglion cells. Targets/Pathway of Ganglion Cell Axons 1. LGN (thalamus) Visual perception - Major target of most GCs - Visual pathway 2. Suprachiasmatic nucleus (hypothalamus) - Cirdadian rhythm Non-image forming 3. Prectum (midbrain) functions - Pupil responses 4. Posterior nucleus of the thalamus - Photophobia 5. Superior colliculus - Eye movements ð Speciﬁcally, when light hits INTRINSICALLY PHOTOSENSITIVE the melanopsin in the outer GCs segment of the cone for a intrinsically photosensitive ð Respond to light by depolarising GC, the cascade leads to the ð Have much much larger receptor TRPC 6/7 channel to open ﬁelds than both the parasol and midget GCs Light causes the depolarisation of ganglion Respond to light even in a blind cells, while it causes the person. hyperpolarisation of cone/rod photoreceptor ð Have an opsin called melanopsin cells. ð Like rhodopsin for rods, when light hits melanopsin, there is an We know that melanopsin can create intracellular cascade that leads to a intrinsic light sensitivity within GCs, channel opening, to allow for the because the RGC response in a blind inﬂux and e\lux of sodium and mouse with melanopsin expressed, potassium ions, forcing a produces excitation (many firing of FUNCTION 1 of ipGCs: Concentral Pupil Response depolarisation. action potentials) of (ISGCs) ganglion ð When light is shone in one eye, it restricts both theresponse cells in eye thattoislight. being shone with light and the remaining eye (both eyes) ð When the sphincter puillae restricts, the pupil restricts. ð So when light is shone in the eye, an intracellular circuit will result in either the constriction of the sphincter pupillae muscles, or the relaxation of the dilator pupillae muscles. So, what is the pathway of photosensitive GCs in a pupil response from shining light? 1. Pathway involves the Melanopsin GCs projecting to the Optical Pretectal Nucleus (OPN) which is a pathway that DOES NOT cross at the optic chiasm, but stays to its’ own respective ‘eye lane’. Just before the LGN, the axon turns inward to project to the Pretectal nucleus. 2. This axon projects to the Pretectal nucleus which then sends a neuron projected to the Edinger Westfal nucleus in the midbrain on its own side and the opposite side as well. The Edinger Westfal nucleus is the parasympathetic innervation to the eye. 3. The Edinger Westfal Nucleus then send a neuron axon back to the iris of the eye, which is what allows for the constriction and relaxation of muscles within the eye for the pupil response IN BOTH EYES. THIS IS WHY WHEN YOU SHINE LIGHT INTO OTHER EYE, YOU CAUSE CONSTRICTION OF BOTH EYES. Therefore, the intrinsically photoreceptive GCs are very important in the constriction and relaxing of the pupil REGARDLESS of photoreceptors. FUNCTION 2 of ipGCs: Circadian Rhythm ipGCs target the Superchiasmatic nucleus of the thalamus. - Contains many nuclei that automate the unconscious functioning of the body, such as sleep & mood. LECTURE 6 – WEEK 3 – WHY DO WE NEED VISUAL ADAPTATIAN? Lecture concept: Our vision depends on our ability to detect small differences or changes in: - Intensity - Position - Colour …where this ability must be maintained under different light levels n Sunrise to sunset What is adaptation in the visual system? ð Where the visual system adjusts its performance to changes in light levels (e.g ambient). Adaptation acts to match the limited neuronal response range to the visual input range. ð Most of the work is done by the scotopic (rods) & photopic (cones) systems. { VISUAL ADPATION } Light Adaption Dark Adaption Beneﬁcial Detrimental Increases visual sensitivity “recovery” in darkness following Rapid process (seconds) light exposure ð From darkness to light. Slow process (~ 40 mins) From light to darkness Weber’s Law: ‘The minimum increase of stimulus which will produce a perceptible increase of sensation is proportional to the pre-existent stimulus”. - The Lowest threshold in terms of illuminance adaption ability is greater for cones than it is for rods, although cones adapt faster than rods when the light is initially shone onto the retina. Rod Adaption: Rods adapt are restricted range of intensity before they saturate (1-2 log units) (so they reach saturation). Yet, they are still able to respond in backgrounds of moderate intensity, and quite well in red lighting. Cone Adaptation: Adapt over a great range of intensities, and DO NOT REACH saturation. [Ca2+ independent adaption] *Accounts for majority of light adaption response* ð cGMP opens the gate required for Ca2+ inﬂux in the light via the activation from PDE. Low PDE means less cGMP to open the Ca2+ channel open. ð Powerful negative feedback loop ð A drop in Ca2+ in response to light avoids saturation hence increases photoreceptor sensitivity. This is mediated by the unbinding of Ca2+ from GCAPs (Guanylyl cyclase activating protein), calmodulin & Recoverin. Guanylyl cyclase activation Recoverin and R* inactivation n Less Ca2+ leads to a shortened R* lifetime n R* is inactivated by rhodopsin kinase (GRK1) in a Ca2+ dependent manner The GCAPs & Recoverin are shared between rods and also cones. Ø CNG channel proteins (the proteins on the GCPAs that regulate Ca2+ binding) For rods: Cna1/Cnb1 For cones: Cnga3/Cngb3 ð In Cones the 11-cis retinal is recycled by RPE cells and Muller Glia Cells, while rods only get the recycled 11-cis retinal from the RPE cells. HAVING TROUBLE BATTING IN CRICKET AND TEMPORARY BLINDNESS WHEN LEAVING A CINEMA: = Bradyopsia Bradyopsia is known as ‘slow vision’, > caused by mutations in the RGS91 or R9AP genes, which results in difficulty adapting to sudden changes in bright light and difficulty in seeing moving objects at low contrast. - RGS91 (expressed in Retina)/R9AP (expressed in brain) are genes involved in the recovery of photoreceptors after light exposure. ð Interestingly, people with this mutation have better/faster night vision as people with no RGS91, PDE is more at low light levels -> shorter turnover of cGMP -> cGMP channels remain open at low light. ð LECTURE 7 – WEEK 3 – WHY DO WE NEED VISUAL ADAPTATIAN? Lecture concept: Our vision depends on our ability to detect small differences or changes in: What is the RPE? Location: The RPE is a single layer of pigmented cells that lies between the photoreceptors (rods and cones) of the retina and the choroid, which is the vascular layer of the eye that supplies blood to the retina. Pigmentation: The cells of the RPE are heavily pigmented with melanin, which gives them a dark appearance. This pigmentation helps to absorb excess light, preventing it from scattering within the eye and thus improving visual acuity Further functions; Absorption of light (heat); barrier function; transport of nutrients, ions and water; phagocytosis of shed OS; Photopigment recycling (all-trans-retinal to 11-cis-retinal) INHERITED RETINAL DISEASES Ø Rare genetic disorders Ø 300+ genes Ø Di\erent genes can cause the same disease phenotype, and then the same gene can cause di\erent disease phenotypes, even within the same family. TYEPS OF HERTITABLE EYE DISEASES (1) Monogenic (Mendelian) - Inherited retinal diseases with 1 pathogenic gene variant - Di\erent genes can be responsible for the same condition in another individual (2) Complex conditions - Condition caused by variants in more than 1 gene variant AND Environmental factors. - An example of this would be age-related macular degeneration, inﬂuences by both genetic factors and environmental and lifestyle factors (including diet, smoking, BMI) - Environmental factors can include chemical and radiation damage (UV light, smoking etc.) that may cause mutation in genes - Genetic factors include errors in DNA replication or errors that arise during recombination in meiosis. Genes encode for proteins, and when a mutated gene encodes a protein it results in either no protein, or an altered protein. Autosomal recessive: Where a parent who has one faulty gene copy and one normal gene copy, is a carrier and does not usually have symptoms. Ø ARIRD = Autosomal Recessive Inherited Retinal Dystrophy n For a child to be aaected, both parents would need to be carriers of a gene variant I the same gene. If both parents are carriers, child can be: - 25% chance aaected - 25% chance unaaected and not a carrier - 50% chance will be an unaaected carrier. EXAMPLE 1 of ARIRD: n ABCA4-related IRDs ð ATP-binding cassette transporter 4 ð Involved in the recycling of 11-cis retinal into all-trans retinal ð sits in the rim of the outer segment of the photoreceptor ð Does so by ﬂipping N-retinylidene phosophatidylethanolamine (NrPE) in photoreceptor disc membrane and prevents build up of vitamin A derivatives, which are toxic to the RPE ð Has 50 exons: An exon is a segment of a gene that codes for proteins. In the process of gene expression, the DNA sequence of a gene is transcribed into messenger RNA (mRNA). This mRNA transcript contains both exons and introns (non-coding regions). During a process called splicing, introns are removed, and the exons are joined together to form the final mRNA sequence that is translated into a protein. ABCA4-related IRDs > can cause Stargardt disease (muscle atrophy), retinitis pigmentosa (form of cone dystrophy), and cone-rod dystrophy. ð When ABCA4 is not present, it results in a build-up of vitamin A, which is where RPE breaks down (pigment epithelium cells in between the photoreceptors of retina and the choroid. Autosomal Dominannt: Where the phenotype trait it seen in those with one copy of the variant. Ø 50% chance of aZected person to pass faulty gene onto child Mechanism of disease: 1. Loss of function – one copy of gene active means it is not enough to maintain normal function 2. Dominant negative & gain-of-function – if one gene is defective and other is not, the defective gene can still impede the normality function of the normal gene. EXAMPLE 1 of ADIRD: n Rho-related retinitis pigmentosa (rod-cone dystrophy) - Rho encodes for rhodopsin - 20-30% of AD rod-cone dystrophies - AD inherited retinal diseases less frequent than autosomal recessive (AR) diseases – also less severe than AR and X-linked. X-Linked: Faulty gene on the X chromosome Ø Female with faulty x chromosome usually do not show symptoms (x- inactivation) Ø Males will, as they only have 1 x X-chrome Ø No male to male transmission If mother is carrier but father is healthy: ð Each son has 50% chance of being aaected ð Each daughter has 50% chance of being a carrier lie mother. EXAMPLE 1 of X-linked-IRD: n Retinitis X-linked-pigmentosa GTPase regulator - Found in photoreceptor outer segments - Essential for the maintenance of photoreceptor viability Mitochondrial inheritance: Ø Mitochondria have their own DNA – 37 genes Ø Mutations in mitochondrial genes passed on through the mother (maternal inheritance) Ø Both males and females can be aaected TYPES OF GENETIC VARIATIONS (MUTATIONS) 1. Aneuploidy – deviation from normal diploid pairs of 23 chromosomes (downs) 2. Structural variants – a\ect whole chromosome or large segment 3. Small variants at the single nucleotide level – a\ect a deﬁned position, most inherited diseases are small variants. Diagnostic testing Find the variation in underlying condition Conﬁrm or rule out suspected genetic disorder TYPES OF GENETIC TESTING: 1. Karyotypes & Fish – are there 23 pairs of chromosomes, like for downs? 2. Microarrays – Better resolution than chromosome-level analysis and looks at thousands of genes simultaneously to study gene activity. Various biological markers can be associated with various health traits. 3. Sanger sequencing – ﬁrst generation sequence method. Can only do single genes, and is very speciﬁc (gene mutations linked to breast cancer) 4. Next generation sequencing – massive parallel sequencing, millions of DNA fragments. Gold standard for CHILD ONSET DISEASES. Standard diagnostic method of sequencing for inherited retinal diseases) typically, 6/10 people can get diagnosis by genetic testing for eye stu\s) Can pick up single nucleotide changes from within the millions of DNA fragments. Next generation sequencing 1. Targeted sequencing – single genes/small regions of DNA 2. Whole Exome Sequencing – sequences protein coding regions 3. Whole genome sequencing – analysis of whole genome Other applications of genetic testing Carrier testing (can mutation be passed to children) Parental testing (detect genetic abnormalities in fetal DNA before birth) Newborn Screening Predictive testing (like to search for genes for things like breast cancer) Pharmacogenetic testing (how genetic makeups respond to di\erent medications) LECTURE 8 – WEEK 3 – THE BIONIC EYE Lecture concept: THE BIONIC EYE 1. Camera – capture images and transmits data to an external, body worn processing unit 2. Data processed – and sent to implanted system via external wire 3. Implanted receiver – passes signals onto retinal implant 4. Implanted electrode array – stimulates retina 5. Electrical signals sent from retina via visual pathway to vision processing centres in the brain. ð The electrodes of the bionic eye take over the natural job of the photoreceptors. Ø If the eye is blown out and there is no optic nerve to innervate, better to directly attach to the brain centres, otherwise you’d target the eye: RETINAL PROSTHESES A. Epiretinal electrode – on top of retina B. Subretinal electrode – behind retina C. Suprachoroidal electrode – behind blood supply at back of retina (most done in Australia) -> In surgery for this one, you make an insertions at the side of the eye to input the electrodes. D. Intrascleral electrode – pocket within the sclera PATIENT OUTCOMES – From first bionic eye tests – for patients with END STAGE retinitis pigmentosa, with only BARE LIGHT PERCEPTION VISION Ø Some improvement in central vision but the vision resulted In general, devices are good for: was not good enough to warrant - Improving light detection and the risky surgery orientation So…Cortical implant! (people who do - Allowing some independent not have an eye – bypass straight to the mobility brain) - Improved object detection n Second sight > cortical (tabletop items) prosthesis in blind participants - Best performance can often recognize large letters or shapes. - Aid in obstacle avoidance OPTOGENETICS – gene therapy Ø In RPE photoreceptors are degenerated (die), but the other retina cells are intact, and so one could innervate them to make them light responsive. Ø One takes a light sensitive protein from an algae, and then takes the gene and inserts it into the DNA of speciﬁc neurons in the brain, to allow for bipolar and ganglion cells to become light responsive themselves. The protein from the algae, is an ion channel that opens in response to blue light and allows for depolarisation. Ø What does this mean? => This means that you can cause neurons to ﬁre just by ﬂashing blue light!! LECTURE 9 – WEEK 4 – NON-INVASSIVE ASSESSMENT OF THE EYE Lecture concept: NON-INVASIVE ASSESSMENT OF THE EYE Binocular vision = Sharing of visual pathways from both eyes in separate hemispheres (left side of each eye is processed on the right hemisphere & right side of each eye is processed on the left hemisphere) This gives us the ability to locate things in space much better. MEASURING RETINASL / CORTICAL ACTIVITY FOLLOWING LIGHT STIMULATION – METHODS: (A) EOG (electro-oculogram) Purpose: Measures the electrical potential difference between the front and back of the eye (RPE). n How well the RPE is working (how well RPE can recycle ‘retinal’, how well RPE can absorb light & how well it can phagocytose outer segments of photoreceptors n Vitreous & cornea has the same potential as the retina, so an active electrode can go on the cornea itself or very close to it, as the bone and skin around the eye also have the same potential as the outside of the eye (inactive electrode can be placed on skin) n Two electrodes, one on left side of eye and one on right side to measure the electrical potential diWerence. ð Because the voltage di\erence is directional from back to front of eye, and by moving the eye (+- 30°), you can produce a measurable di\erencing signal. ð So, you can take a sample of the resting potential of the eye after eye movement (left and right), and then take the diGerence from those two extremes. ∴ difference potential = difference between left and right gaze movements (potential). Ø Light peak/dark trough Ø = normally >2.0 Ø Maximal K+ bu\ering capacity of the RPE Arden Ratio is smaller when… - There is not enough vitamin A - Diseases of RPE - Diabetes when RPE and retina are sick - Retinal dystrophies Best’s Disease = ratio 1:3 A-waves = come from photoreceptors ð The size of the peak is determined by how many photoreceptors are activated by the light. ð The change in peak to asymptote (the steepness of the drop in a to the peak in b) is determined by how quickly the rhodopsin/opsins initiate the closing of cGMP channels (for NA+) ð The faster the ampliﬁcation, the faster the cGMP channels are closed. B-waves = come from bipolar cells CONTINUATION of A & B waves… ð If the A wave is normal (from trough to main peak), but the B wave is not (slow and shallow), there may be a problem with either the mGluR6 receptors of the bipolar cells, or the ability of the bipolar cells to transmit the signals onward. MEASURING RETINASL / CORTICAL ACTIVITY FOLLOWING LIGHT STIMULATION – METHODS: (B) ERG (electro-retinogram) Purpose: Measures the electrical activity of the retina in response to light stimuli. The scotopic threshold response (STR) is a key measure in assessing the sensitivity and function of rod photoreceptors in the retina under low-light conditions. It is used in diagnosing and monitoring retinal diseases, particularly those affecting night vision and rod function. The term “threshold” refers to the minimal level of light intensity required to elicit a detectable electrical response from the retina. The STR measures the response at this threshold level, providing insights into the sensitivity and function of the rods. ð If you were to block the bipolar cell response to light stimuli (by using L-AP4) what it shows is that there is only the a-wave left (no-b- wave) = Bipolar cells are required for the b-wave ð Blocking ganglion cells with tetrodotoxin does not impact the correct wave of amplitude of (a) or (b) waves. ð Injury to fovea, also results in a loss of signal. (C) VER/VEP (visual evoked response) Purpose: Measures the electrical activity of the visual cortex in response to visual stimuli. Can be useful for: n Visual acuity in children n Amblyopia n Albinism n Intactness of visual pathway (stroke, MS e.g.) ð Normally, 50% GCs axons crosses over to the other side of hemisphere, with the L or R signal giving the biggest signal in the centre electrode: ð No decussation (decussation = crossing of GC axons) occurs in albinism, where the L or R signal give larger signals on the electrode. This is known as lateralisation of VEP signal. Another thing one can do with VEP > Record Vep amplitude as stimulus switches form black and white Keep making the check smaller until there Is no more signal The spatial frequency is converted to visual acuity ð SO basically, it means to make check sizes smaller and smaller until the person cannot really diWerentiate visually between the black and white squares = a measure of visual acuity: SUMMARY OF OCULAR ELECTODIAGNOSTICS – FOR EXAM! *HAND HELD ERG – Can be used to detect seizures and genetic predisposition to seizures in children* EXAM QUESTION – WHICH WILL BE ON THE EXAM!!! LECTURE 10 – WEEK 4 – VIRAL VECTORS & RETINAL GENE THERAPY Lecture concept: What is gene therapy, and what can it do? Gene therapy: Experimental technique that uses genes to treat or prevent disease. Can be used for: Replace mutate disease-causing gene Viral Vector: Gene inactivation A viral vector is a virus that has been Introduce a new gene to help ﬁght disease genetically engineered to carry Generate secreted proteins therapeutic genes into target cells without causing disease. These vectors are used to introduce new or modified EX VIVO => Gene therapy where targeted cells are genes into cells to correct genetic removed from body, altered, and then transplanting disorders or treat diseases. them back not patient. IN VIVO => Gene therapy where direct systemic n Vectors are made safe by administration (intravenous) to the patient wherein removing viral genes. the targeted cells remain the body. Choice of virus to use depends on: How well virus is understood How well virus can target certain cell types è Small How safe virus is to use è Replication-deﬁcient (without an adenovirus/helper virus, this virus cannot replicate = good thing) TYEPS OF AAV CAPSID è Single-stranded DNA genome INJECTIONS (RETINAL) è Around 120 human and non-human serotypes. 1. Subretinal injection - within the ‘bleb’ that is created between the PROS: retina and vitreous ð AAV8 (green ﬂuorescent protein) – highlights both the RPE layer and photoreceptor layer. 2. Intravitreal injection – Into the vitreous ð AAV2 (green ﬂuorescent protein – CONSIDERATIONS: highlights ganglion cell layer) - Developing A Gene Therapy – Understand the biology of the disorder [CURRENT CHALLENGES FOR OCULAR THERAPY] Develop treatment approach è Introducing the right of AAV into the body Test e\ectiveness in biological models of disease Establish safety è Correct for introducing AAV è Speciﬁcity and e\icacy of current vectors è Delivery: Subretinal vs Intravitreal è Pre-existing immunity (PEI) and acquired immunity è Large genes è Clinical outcome measures Hard to assess how much of defective/missing protein we need in humans, but, visual rescue of animal models of retinal degeneration with mutations in high expressing genes is possible. How could we improve this? ð Better vector design (promotor, improved AAV capsids, gene sequencing optimization ð Clinical trials comparisons n PDE6B gene therapy (treated mice at 9 days of age, able to recover most of eye cells like rods and ganglion cells, where an increase in the PDE6B gene allowed for retinal recovering) – Same thing was done in the rods of dogs. Natural history of disease Onset Progression Mutation-speciﬁc e\ects Inter-individual di\erences E\ect of environmental factors. n CNGB3 gene therapy (treatment for cones with CNGB3 gene – complete loss of colour vision which is rescued by introducing greater CNGB3 proteins) – mice that were treated at day 30, recovered colour vision as well as the regular wild- type mice’s vision – while when treated at day 150, the recovery was only minimal and not a normal physiological colour vision) è Achromatopsia: Rare genetic disorder that results in the complete or partial loss of colour vision. Development of better vectors / AAV biology Alternative serotypes / species Physico-chemical modiﬁcation Capsid engineering (mutagenesis; rational design; directed evolution; in silico design) FIRST APPROVED IN VIVO GENE THERAPY WAS FOR AN IRD è LUXTURNA (voretigene neparvovec) - LCA è RPE65 mutations è Rare congenital inherited eye disease (1 in 40,000) è Symptoms appear at birth or in ﬁrst few months è Severe vision loss / blindness è First FDA approved therapy è Gene located in 1993 > therapy only into fruition in 2016 LECTURE 11 – WEEK 4 – RETINAL MOSAIC & SAMPLING Lecture concept: How does the retina sample visual space, and how does this relate to the anatomical structure of photoreceptors & ganglion cells? ð Smallest population of S-cones (only 10% of all cones in retina, the rest is M & L) ð Spatial resolving capacity of retina / visual system will be related to photoreceptor spacing. ð Resolution limit is approx. 40 to 60 cycles / degree. ð At 30 cycles/degree vision is at ‘20/20’ which means great resolving capacity and visual acuity, at 3 cycles/degree vision is at ‘20/200’ which means much lower resolving capacity. Angular Subtense Angular subtense refers to the angle that an object or feature subtends (or covers) at the eye from a given distance. Essentially, it describes how large an object appears to be from the observer's viewpoint. Measurement: Angular subtense is measured in degrees (°), minutes (′), or seconds (″) of visual angle. One degree is divided into 60 minutes, and one minute is divided into 60 seconds. Example: If you are looking at a coin that is held at arm's length, the angular subtense of the coin would be the angle formed between the lines of sight from your eyes to the edges of the coin. An increased spatial resolution can be seen where there is the greatest density of cones (fovea). > increasing amounts of blur in the vision as you wane of the central axis (degrees) – (into side vision – we have poorer vision off to the side). GRATINGS = Wave of vision that intersect and create ‘gratings’, course grating has lower spatial frequency while fine grating produces much great spatial frequency. Course grating = black and white stripes, more extreme contrast needed. Fine grating = feint grey stripes, no extreme contrast between black and white needed to see. Retinal Periphery > beyond 5 eccentricity, suggests there to be a resolution limit in retinal periphery set by neuronal factors (retina/brain). RGCs pool signal from multiple photoreceptors in retinal periphery – should set resolution limit, therefore, the GCs instead of photoreceptors in the periphery specifically that are the limiting factor of our spatial resolution. Between the photoreceptors and the GCs, where there is the lowest density correlates to the factor which is impeding spatial resolution. However, it is actually the midget-GCs (parvocellular) which limit our vision (80-90% of RGCs) - Smaller dendritic ﬁelds - Smaller centre-surround receptor feilds - Complete coverage of all eccentricities ‘In the context of vision, aliasing refers to the distortion or misrepresentation of visual information due to limitations in the spatial resolution of the visual system. It occurs when the frequency or detail of visual stimuli exceeds the resolving capacity of the eye or visual system, leading to artifacts or misleading perceptions.’ Aliasing – Ø Results from inadequate sampling of continuous function (e.g under sampling) Ø Signal reconstructed from samples differs from original, continuous signal Ø Alias typically has lower spatial frequency & different (i.e. non- veridical) orientation. So, you will get weird tiger-stripe like vision when the spatial frequency is too high to be able to resolve, so a spatial frequency that is ABOVE THE NYQUIST LIMIT. Samling frequency must be at least twice the highest spatial frequency to adequately represent signal. - in central fovea, L- & M- cone density high enough to capture all the information that survives the blurring by eye's optics - blurring by eye's optics helps prevent aliasing - in retinal periphery (lower cone density), effect of aliasing reduced by the disarray in sampling mosaic = produces noisy pattern rather than plausible object - aliasing (and other) studies have revealed an S-cone spacing of 10 minutes of arc, and L- & M-cone spacing of 30 seconds of arc WHY ARE S-CONES SO SPARSE IN COMPARISON TO M/L CONES? è Chromatic aberration in eye blurs short-wavelength image è Sparse sampling is adequate to capture retinal image seen by S-cone mosaic è Blue bends better (refracts better) – eyes are a little bit short sighted for blue light (little bit out of focus on the retina), always produces ‘fuzzy’ image, so why would the eye want more of them (s-cones)?? That’s the logic ^. LECTURE 12– WEEK 5 – IMAGING RETINAL CELLS Lecture concept: How do we take images of the retina and what does this show us? THE TRANSPARENT RETINA GOLGI STAINING è Silver nitrate è Golgi & Cajal – 1887 è Argued whether photoreceptor to GC pathway was a single cell or parts of the same reticular network or nervous tissue. è Contrast is essential to see things. è In the living eye the options for increased contrast are more limited n Photoreceptors are the easiest to image (with RBCs being the easiest cell to image n Retinal pigment epithelium (RPE) – beneath photoreceptors, and are hard to image. FOR BEST IMAGING: Bigger pupils = better to image ^ This is because of the e\ects of ocular aberrations, and the e\ects of di\raction….SO, what do we do about this? There exists a deformable mirror which can compensate for ‘wavefront aberrations’. This is done by the mirror being wavy in shape, and so the refracted light which hits it (in wavy form) the wavy mirror, then re-bends the light to a straight light image: What now? > Ok so the light has been corrected by the deformable mirror, and those waves of light are then ‘imaged’ (photo of this light is taken by a camera), to determine what image the light is producing (in this case imaging the surface of the retina) S-L-M cone identiﬁcation can be made with a VERY time-consuming bleaching method. So, how do we actually capture an image of the retina which does not take forever? -> We can image CHANGE (imaging contrast of change). SPEED is important in taking images to get proper contrast of movement. Need temporal & spatial resolution. = Motion contrast image. SCANNING LASER MICROSCOPY / OPTHALMOSCOPY Scanning laser ophthalmoscopes (SLOs) are fundamentally the same as scanning laser microscopes (SLM) Only di\erence is that in SLO the optics of the eye serve as the objective lens and the fundus is always the sample. (1) In a SLM/SLO light is focused to a point on the sample of interest (2) light that scatters from that focused point is measured with a sensitive light detectors (PMT or APD). (3) To form an image, the light is continually recorded while the focused spot scans across the sample, generally in a raster pattern (4) Positional information from the scanners is combines with the intensity information from the detector to form the image. SCANNING/DESCANNING è The fact that the returning light is rendered stationary after descanning allows us to place a confocal aperture prior to the PMT detector. What is the point of this? è Because... we are trying to illuminate only one spot on the retina, only one place of illumination, and try to focus it on a very very small point. Then the light is collected, and you only collect the light that is focused on the CONFOCAL APETURE, which is a tiny little whole which is projected onto a detector. LECTURE 13 – WEEK 5 – WINDOW INTO CNS Lecture concept: The eye as a window to the CNS Fundus Camera = 2D Retinal Photo Optical Coherence Tomography = 3D Retinal Scan Ø Achieved through combining many A-scans to create a B-scan, and then combining many B-scans to create a C-scan (or Optical coherence tomography) which is a 3D model! Ø This allows for a capillary level image at high resolution. ADVANTAGES OF RETINA – (ERG) Electroretinography Simple 3-tiered neuronal structure Well organised and deﬁned Measured with electroretinography (ERG) Similar blood neural barriers è Blood neural barrier: blood brain barrier and blood retinal barrier è Protects neurons, strict regulation of substances from the blood stream è Mechanical barrier: formed by tight functions by: - Occluding - Junctional adhesion molecules (JAM) - Claudins è Metabolic barrier: - Glucose transport mechanisms: GLUT1 & GLUT3 - Speciﬁc amino acid protein transport systems But, there is both the inner & outer blood supply to the retina, with two distinct barriers… TWO DISTINCT BARRIERS (1) Inner – endothelial cell tight junctions in vasculature (2) Outer: tight junctions between retinal pigment epithelial cells > tight junctions form in the RPE layer, the choroid space that follows is a space which has free-liquid, so no tight junctions are there (choroid is ﬁrst layer after the outer BRB). EYE MARKER FOR DIABETES è Loss of retinal pericytes è Basement membrane thickening è Capillary microaneurysm formation è Increased vascular permeability > exudation and tissue oedema è Ischemia lead to retinal neovascularization è Arteriolar narrowing è Generalizes retinal thickening and arteriolar tortuosity è Blood retinal barrier breakdown (haemorrhages, exudates, nerve ﬁbre layer ischemia (looks like cotton wool spots on the retina) è MS: inﬂammatory demyelinating disease è Less retinal ganglion cells Thinner retinal nerve ﬁbre layer (optic nerve) Thinner ganglion cell complex (macula) Long established occurs with optic neuritis è CURRENTLY, have to determine through post-mortem è PET imaging useful but expensive è OCT: Thinning of retinal nerve ﬁbre layer Thinning of macula, ganglion cell inner plexiform layer Difference between eye markers for Alzheimer’s vs MS – what is unique to Alzheimer’s disease in markers: ð Hallmark is amyloid-beta plaque deposition in the brain ð Amyloid-beta plaque will show up in the retina of a person with Alzheimer’s. PASRKINSONS’ DISEASE n 2nd most common neurogenerative disease n Non-motor symptoms: olfactory & vision n Pathophysiology: loss of dopaminergic neurons in substantia nigra, Lew bodies containing a-synuclein OCT – The Results! - Changes in outer layer retinal layers - alpha-synuclein deposits - thinning of retinal nerve ﬁbre layer and macula thickness ERG – The Results! - ERG reduced in patients - A-wave, b-wave, oscillatory potentials - ERG losses ameliorated by L-DOPA therapy LECTURE 14 – WEEK 5 – BACSIC CONCEPTS IN SYSTEMS NEUROSCIENCE - NEUROTECHNIQUES Lecture concept: How do we study neural systems and its relation to ion channels in psychophysics BROADMAN – Ø Identiﬁed number of di\erent areas in the brain, where all cortex has 6 main layers/ Ø V1 = Striate Cortex = Area 17 (located at the back end of the occipital lobe) Ø Suggests a di\erence in function compared to other brain areas THEORIES of localized brain function: (1) Franz Josef Fall – gave areas functions such as ambition, calculation and spirituality, where each are could increase as a result of use [referred to as ‘bumps’] (2) Karl Lashley – spent 35 years searching for the ‘engram’ > asked where are memories stored? è Memories for complex tasks are stored DIFFUSELY throughout the cortex ‘principle of mass action’ è All parts of the cortex play an equal role in memory storage ‘principle of equipotentiality’ An engram is a theoretical construct in neuroscience that refers to the physical or biochemical changes in the brain that are associated with the storage of memories. It's often described as a "memory trace," representing the neural substrate of memory—essentially, how memories are encoded, stored, and later retrieved within the brain (3) Penﬁeld - a neurosurgeon who helped people with epilepsy, provided evidence for localized brain functions through this experiments of brain stimulation. è mapped whole somatosensory cortex è post central gyrus – sensations in body parts which is the somatosensory cortex, where the post central gyrus runs from the dorsal level to the caudal level of the brain è found out that the cortex is somatotopic (somatosensory homunculus) è Temporal lobe > elicit melodies, and other auditory events è Occipital lobe > visual events ð Motion blindness ð woman with headaches gets CT, shows vascular disorder, showed damage to cortex at border of occipital lobe and temporal lobes (Area MT / V5) ð presented problems perceiving motion from vision; auditory and tactile motion cues could be used as normal, there was a COMPLETE [In LTP] DISSACOTIATION. ð Further problems with reading people’s lips when they are talking, and had trouble determining when the cup of water one was drinking out of was empty. Ø NMDA channels (voltage gated channel)– allow for the inﬂux of Ca2+ into the PSCell (when magnesium is unbound from this channel, then calcium can enter cell!). Ø AMPA channels – allow for inﬂux and e\lux of K+ and Na+ > Na+ inﬂux through AMPA receptors, cuases an ESP (depolarisation current) which can leads to LTP. WHAT DOES CALCIUM DO IN LTP? ð The more calcium that enters the cell through the NMDA channels, the more sensitive the AMPA channels become to glutamate, and therefore the more sodium can enter the cell over time… ð Calcium entering also activates the SILENT channels which are on the PSMembrane, increasing sodium intake into the cell when the pre ﬁres on the post. Synaptic plasticity: Phosphorylation plays a key role in processes like long-term potentiation (LTP) and long-term depression (LTD), which are mechanisms for strengthening or weakening synaptic connections. For instance, certain kinases, such as Ca²⁺/calmodulin-dependent protein kinase II (CaMKII), can phosphorylate NMDA receptors during LTP, leading to enhanced synaptic transmission. What is special about the brain of modern humans? The human brain has a high rate of spatiotemporal parsing Reading is a good example of this, where the brain is activated in a unique way showing a high spatiotemporal parsing. LECTURE 16 – WEEK 5 – PARELLEL PATHWAYS Lecture concept: How ð The midget/parvo and parasol/magno channels remain segregated until primary visual cortex. è Having both the ON and OFF systems reduces metabolic total cost. è ON centre cells respond to positive contrast è OFF centre cells respond to negative contrast CONTRAST SENSITIVITY One cycle is constituted by Michelson contrast = (Max-Min) / (Max + min) one white + one black contrast together. SO – The more gratings (cycle of gratings) there is detected, the GREATER the SPATIAL FREWUENC è Magnocellular (Parasol RGCs) are very sensitive to CONTRAST & Y! MOTION, parvocellular (midget-ganglion cells) are not nearly as sensitive to contrast. è Magnocellular cells can detect contrast at sensitivity of 0.1! SMALL BISTRATIFIED CELLS – The small bistratified cell is known to carry signals from short wavelength-sensitive (‘blue’) cones to the brain > which project to the KONIOCELLULAR layers of the LGN. Ø Simple low-pass ﬁltering (blurring) causes Konio bridges across P layers to become apparent) Konio bridges refer to the thin intercalated connections or pathways between the koniocellular layers in the lateral geniculate nucleus (LGN) of the thalamus. These bridges are thought to link or bridge between different koniocellular regions, facilitating communication across layers and contributing to the relay of visual information. In the LGN, the koniocellular layers are interspersed between the main magnocellular and parvocellular layers, and these koniocellular "bridges" or connections help distribute visual information processed by the koniocellular pathway, particularly related to blue- yellow colour vision and possibly other visual functions like motion perception. IN LGN: ð Segregation of red/green opponent cells to PARVOCELLULAR layers, and blue/yellow opponent cells to the KONICELLULAR regions. ð THIS SHOWS US: That all 3 colour systems, the (1) colourblind system (Magno), the (2) red/green colour system, and the (3) blue/yellow colour system, are ALL SEPERATED FROM EACH OTHER AND REPSOND TO DIFFERENT WAVELENGTHS OF LIGHT. LECTURE 17 – WEEK 5 – VISION & BALANCE Lecture concept: (1) The vestibulo-ocular response (VOR) is a reﬂex that stabilizes the eyes when the head moves. It is driven by signals from the vestibular system in the inner ear, which detects changes in head position and movement. è VERY IMPORTANT IN PRIMATE EVOLUTION! (unlike optokinetic responses) n Vestibulo-ocular response is more to do with the ‘self-motion’ and how this helps us separate animals from plants for example. SO, what drives the VOR? - Driven by inner ear balance centre (vestibular system) - Sensory transduction here produces a signal which drives both the eyes binocularly Ø The movement of the head triggers the inner ear balance centre Ø Vision does not trigger the response -> can demonstrate this by recording someone’s eye movements as they rotate their head in total darkness. Ø The vestibular apparatus responds most directly to acceleration, where one (1) set/part of the vestibular apparatus is more sensitive to rotary acceleration & another set more sensitive to linear acceleration (includes gravity, which makes this a crucial sense for gravity) è Wide-ﬁeld visual motion elicits a sense of self motion – evidence of the optokinetic pathway’s input to the vestibular system è Makes sense evolutionarily because we have evolved for the two di\erent pathways to work synchronously in order to stabilize gaze (2) The optokinetic response (OKR) is a reﬂex eye movement that occurs in response to the motion of the visual ﬁeld. It helps stabilize the image of a moving scene on the retina, allowing the brain to maintain a stable perception of the environment even as the ﬁeld of view moves. - More important for rats then monkeys for example, as with rats they have lateral eyes and small binocular vision – the visual scene streams past the eyes, and so the OKR is very important (the world seems for the rat that it is moving past us, while for the monkey it would seem that we are the one moving through the world. What is the optokinetic response for humans? n Slow eye movement follows the moving stimulus n After certain point, a fast saccade re-centres gaze n This repetition of slow, fast, slow, fast, slow is called optokinetic nystagmus EXAMPLE: looking outside a train window as the train travels… Optokinetic = moving image Nystagmus = slow drift, then fast re-fixation n Cells which elicit this response have very large visual ﬁelds, as they don’t really care about ﬁne details, but more so respond to low grade texture changes. ð HUMANS have both the ‘primitive’ AOS pathway which is direct from the retina + we also have the cortical inputs projecting via the geniculo-cortical pathway which feed into the AOS and associated nuclei Differences Between OKR and VOR OKR: Driven by visual input and compensates for movements of the visual scene. VOR: Driven by vestibular input and compensates for head movements. Speed of response: VOR operates quickly, reacting almost immediately to head movements, while OKR reacts more slowly as it is dependent on processing visual motion. Function: Both work together to stabilize gaze. The VOR is more effective during rapid head movements, while the OKR is more suited for compensating for slow- moving objects or scenes in the visual field. SOURCES OF ORIENTATION INFORMATION 1. VESTIBULAR 2. VISUAL è The major way to monitor è High level = known orientation of a scene body accelerations è Low level = bulk motion of a scene (optokinetic) - Both linear and angular accelerations 3. PROPRIOCEPTIVE & KINESTHETIC è huge input to vision, esp. è E.g., joint position, muscle force (via sensors in control of eye movements tendons) è Slowly responding system, salient but not very accurate è (1) Maintain Balance Linear acceleration mostly > e.g. gravity Vestibulospinal reﬂex (2) Maintain gaze despite head movement * Rotational acceleration mostly * Enhances VOR: Stabilize gaze on some target in the world * Supress VOR: Stabilize gaze relative to self (e.g. when you’re reading something your holding but your also moving on a train) WHAT MOTIONS DOES THE VESTIBULAR SYSTEM SENSE? ð (1) Translational motion: along 3 possible axes - Harder to study, as linear accelerations include gravity’s impact n Within the inner ear, just past the actual cochlear spiral, is the inner ear apparatus, where there are patches of both saccule & utricule, which are areas of CaCO3 (calcium carbonate) crystals, called OTOLITHS (Otolith organs are the patches of combined crystals) WHICH DETECT ROTATIONAL ACCELERATIONS n When the body accelerates, the heavy crystals move which produces drag on the hair cells > This triggers a change in their electrical polarization, converting linear acceleration to a neural signal. n WHY HAVE 2 DIFFERENT CHAMBERS FOR DETECTING LINEAR FORCES? > the utricle and the saccule are orientated in diherent directions, where utricle senses horizontal (coronal) head movements/forces, and the saccule senses vertical head movements (sagittal). ð Age related false detection of vertigo (when one stands they accelerate against gravity and determine the world to be moving when it is not = BPPV (Benign paroxysmal positional vertigo) ð (2) Rotational motion: around 3 possible axes - Can use a swivel chair or gently rotate head, in order to test rotational motion. n Rotations detected by tubes in inner ear ‘semicircular canals’ (SCCs) n SCCs are aligned wo the EOMs (extraocular muscles) > So do not strictly sense any horizontal or vertical rotations of the head, nor are they strictly orthogonal. n There are 2 x semicircular canals, one on either side of the ehad as we have two ears. n Calculate 3D movements. n SCCs ﬁlled with ﬂuid called ‘endolymph’, è In SCC there is the endolymph ﬂuid, and this is intruded by a ‘cupula’ (which is a thick bundle of hair cell cilia that create a gelatinous diaphragm. è When head turns, the canal and cupula move but the endolymph initially stays still due to inertia > This causes the endolymph and cupula to press on each other, bending the hair ﬁbres in the ﬂexible cupula and triggering CELL DEPOLARIZATION. (hair cells do not depolarize themselves, like photoreceptors). è causes Hair cells contain one big cilium in the middle of all the other hair stereocilia known as the ‘KINOCILLIUM’. è When the KINOCILLIUM bends one way it causes the cell to excite (depolarise) and when the cell bends another way it causes hyperpolarisation, where responses are graded. è The cells, like in photoreceptors, drive bipolar cell neurons which will ﬁre the action potentials. è Initally, endolymph lags behinds, but if you rotate for a while at a constant velocity (hard to do in nature) the endolymph catches up with the canal and the cupula straightens. MOVEMENT OF HEAD & ACTIVATION OF THE INNER EAR: When head turns left, ﬁring rate of the left inner ear (SCC) is increased and at the same time the right SCC is inhibited, it is quite antagonistic in nature if you think about it. STEP BY STEP Wiring of the VOR: The 3 neurons arc STEPS by which the signals from the inner ear vestibular system impacts the EOMs to move the eyes: è The scenario is that the head has turned left, and the eyes need to turn right using only the 3 neurons [arc]. è Firstly, the left side SCC senses a left horizontal movement of the head…. th (1) 8 Cranial Nerve (CN8): Composed of axons from bipolar cells which synapse with the hair cells These bipolar cell bodies form the vestibular ganglion CN8 then projects to the vestibular nucleus CN8 carries both auditory and vestibular signal (2) Vestibular nucleus neurons: Project to motor nuclei: (same side CN3 (MR – medial rectus), other side CN6 (LR – Lateral rectus)) (3) Ocular motor nerves (CN3 & CN6) * Drive the EOMs to move the eyes (MR, LR) LECTURE 18 – WEEK 6 – PARALLEL CHANNELS IN VISION Lecture concept: There is one main pathway when talking about vision, from the eyes to the brain. The main is the LGN (will focus on next lecture), which possess a parallel channel in vision… è When talking about the parallel pathways, there are 3 main pathways that carry visual information to the visual cortex. - these pathways are termed ‘parallel’ as they work simultaneously, where each pathway possesses diAerent aspects of the visual scene, which obviously then converge to create an actual image in the brain: (1) – Function: Primarily processes ﬁne visual details, color, and texture. This pathway is sensitive to high spatial resolution (sharpness) and low temporal resolution (slow changes in the scene). Location in LGN: Parvocellular layers of the LGN (layers 3 to 6). Associated with: Ventral stream, which is involved in object recognition ("what" pathway). (1) Magnocellular pathway (Parasol ganglion cell pathway) – Function: Processes motion, luminance contrast, and large, fast-moving objects. This pathway is sensitive to high temporal resolution (rapid changes in motion) but lower spatial resolution (less detail). Location in LGN: Magnocellular layers of the LGN (layers 1 and 2). Associated with: Dorsal stream, which is involved in motion detection and spatial orientation ("where" pathway). (1) – Origin: Small ganglion cells in the retina that are not well defined compared to parvocellular and magnocellular cells. Function: Processes color information, especially blue-yellow color contrasts, but its role is less well understood compared to the other two pathways. Location in LGN: Koniocellular layers, which are intercalated between the parvocellular and magnocellular layers. Associated with: Various functions, including some roles in color perception and other less clear aspects of vision. è These pathways remain SEGREGATED until the primary visual cortex è LECTURE 19 – WEEK 6 – EXTRAGENICULATE VISUAL PATHWAY Lecture concept: IN GENERAL, the visual pathway is where neurons going from the retina to the LGN, and then project to areas like the V1 and other cortical areas of the brain. What we look at today are the pathways from the retina that DO NOT follow this typical route: - Control pupillary responses to light - Mediate some eye movements - Underline some of the responses seen in ‘blindsight’ è Important to remember > EXTRAGENICULATE refers to all the pathways that BYPASS the LGN, hence the ‘extra’. {PATHWAYS, STUCTURES & FUNCTIONS COVERERED BNY THE EXTRAGENICULATE PATHWAY} (1)Pupillary Light Reﬂex Pathway Projects to the Pretectal Nucleus Both eyes project to both pretectal bodies/nuclei > there is one pretectal nucleus on each side (one for each eye technically) THEN; each pretectal nucleus projects to both Edinger-Westphal nuclei (bilaterally projected), which is what provides the motor innervation of the pupillary sphincter. This bilateral projection is important as when you shine a light into either eye, it causes the pupils of both eyes to constrict. CONSTRICTION The near triad: refers to synergistic relation between pupillary constriction, lens accommodation and convergence of the two eyes. - Most of the ciliary ganglion go to the ciliary muscles of the lens so that the pupil can constrict > keep in mind the ciliary ganglion are parasympathetic ganglion, which is why they have the ability to CONSTRICT the pupil. - The near triad is important because if we wanted to look at something CLOSELY, one would need: 1. To keep the visual scene (image) on corresponding same points on both retinas 2. To make the lens power stronger so that its’ in focus on both eyes 3. To get that additional focussing power from the ‘pinhole’ e\ect of a smaller pupil DILATION Dilator activity is a sympathetic nervous system function In the dark (lack of light), pupil will dilate because sphincter muscle is inhibited, and the dilator muscles are excited There are 3 neurons between the hypothalamus and the dilator – it is an adrenergic sympathetic innervation of the dilator muscles: 1. (Neuron 1) – Long neuron, travels from brain to the spinal cord to the eye (through chest/lung area) > disruptions of neuron 1 can cause Horner’s Disease. 2. (Neuron 2) – Neuron which sits in the thoracic sympathetic trunk 3. (Neuron 3) – Neuron which transmits noradrenaline via the a1 adrenergic receptor. This neuron is the pupil dilator! HORNER’S SYNDROME è Supresses sympathetic signals, so we do not get the dilation of the pupil è The neurons which are involved in the sympathetic chain involved in Horner’s syndrome, also innervate the eye-lids and the sweat (sudomotor) & vasoconstrictor branch at the superior cervical ganglion. è Therefore, disruption of this pathway will result in the pupil losing dilation innervation, the lid droops, sweating is disrupted and the blood vessels dilate in the region innervated by this nerve chain. è In summary, pupil responses are driven by multiple factors: light, sense of near and psychological arousal. (2) Accessory Optic System (AOS) è Involves the; nucleus of the optic tract (NOT), medial, dorsal and lateral terminal nuclei (MATN, DTN, & LTN) è Is a visual pathway whose directionally-selective neurones prefer stimuli that are larger and slow-moving. è Part of the OPK nystagmus and VOR pathways, both of which involve motion of much or all of the visual ﬁeld. Optokinetic system - Visually driven - Responds to low frequencies - Can generate sustained responses Vestibular system - Acceleration driven - Responds best to high frequencies - Responses are transient Lets talk about the optokinetic nystagmus… Ø Is rapid involuntary eye movements Ø Deﬁned as: invoked by full ﬁeld motion, slow eye movement in the direction of a moving object and a rapid return of eye position in the opposite direction (3) THE: Superior Colliculus (a.k.a the optic tectum) n Part of the midbrain area n In birds the tectum is a signiﬁcant part of the brain but in humans it’s a little bump on the top of the midbrain. n SC is very important in eye movements, and is clearly a structure well- placed to receive sensory information and produce a motor command. ð HAS 2 VISUAL PATHWAYS (2) DORSAL (3) VENTRAL ð The SC gets direct input from the retina & the visual cortex, parietal cortex and a range of frontal areas, it receives INHIBITION input from the basal ganglia in the frtonal cortex. ð EWerents go to thalamus & cerebellum. Ultimately, the SC is key in the quick orientation of gaze, although it does not tell us what the stimulus is, it allows for us to focus on the stimulus quickly. ð The SC receives many di\erent sensory inputs that are not all vision (hearing etc.), and this is important as these nonvisual inputs to the SC make possible accurate saccades to nonvisual stimuli and allow for the non-visual enhancement of response to a multisensory stimulus. (3) THE: Pulvinar ð The Pulvinar receives inputs from both layers of the SC and projects widely to the various visual cortical areas and to the parietal cortex ð But what does it do? > Converges diWerent cortical areas to work together, by regulating information transmission between these cortical areas depending on our behavioural demands. This can depend on our level of attention apparently. ð Pulvinar nuclei sit on top of the SC, contains 3 visual areas (medial, lateral & inferior). LESION IN PULVINAR = can impair facial emotion processing. A complete lesion on left pulvinar region could not recognise ‘fear’ when represented to his right visual field. So what does this mean? > Well, it means that the neurons within the Pulvinar region seem to react primarily to the expression of emotion by the face. LECTURE 20 – WEEK 6 – VISUAL CORTEX 1 – CELL TYPES & ORIENTATOIN SELECTIVITY Lecture concept: è (1) PYRMARIDAL cells: - Large, dendrites radiate from the base, major axon leaves the cortical area, only these send axons out of the striate cortex (the visual cortex) - Found in all layers of visual cortex except 1 & 4. è (2) INTERNEURONES: - Local projections – stellate, spiny (glutamatergic) & non-spiny or smooth (GABAergic), Chandelier looking (not pyramid looking), double bouquet looking. - Found in all layers n TYPICLALY, pyramidal neuron axons are projected to leave to the cortex to other parts of the brain (subcortical). n Layers 4C and 6 are densest and darkest n Layers 1, 4B & 5 are most loosely packed. n Golgi (1900) used staining to determine the shape of diGerent neurons

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