Special Senses

• Introduction: - The threshold is the amplitude of a sound pressure wave that can just be hear when presented to a listener. The minimum amplitude of a sound wave that can be detected for a normally-hearing individual is 20uPa.
   
  - Sound is measured in units of decibels, and each increment of the sound wave amplitude by a factor of 10 will increment the sound level by 20 on the decibel scale.- The threshold sound stimulus depends on the frequency. The threshold rises at both lower and higher frequencies.- In an audiogram, 0dB represents the minimum intensity that humans can hear at.

  - The range over which we hear is, optimally, 20 - 20k Hz. But this can differ from each individual. At 120 dB (equivalent to a loud rock concert) this is known as a 'high risk' threshold and at 140dB (gun shots) this would be the threshold for pain.

Structure of the Ear:
 - The external ear consists of the visible flap known as the 'pinna', the funnel-like inner portion (concha) and the external auditory canal (meatus). Some animals can move their pinnae to orientate them towards a sound. This is responsible for detecting sound and directing it to the tympanic membrane (eardrum). This is the first stage of amplification.

- The middle ear is a cavity interposed between the tympanic membrane and the foramen ovale (oval window) which opens into the cochlea of the inner ear but retains fluid within it. This area contains the ossicular chain of 3 bones (malleus, incus and stapes) which connect the external and inner ear structures.
- The eustachian tube runs from either side of the tympanic membrane to the pharynx. As the middle ear is air filled, this communication allows the pressure on either side of the eardrum to be equalized to atmospheric pressure when swalling or yawning.

• Structure of the Ear:
  
  - The middle ear is lined with a low cuboidal ciliated epithelium that covers the walls, suspensory ligaments of the ossicles and nerves. It acts functionally as a device which matches the acoustic impedence of the medium through which sound travels to the fluid in the inner ear. This transformer action allows a sound wave travelling in air to become a sound wave travelling in fluid.
  - The tympanic membrane contains tissue fibres to withstand tension which it is kept under by the tensor tympanum muscle (which can also restrict movement of the ossicles). The oval window has 1/20th the area of the tympanic membrane so it experiences a correspondingly greater force per area in response to sound. This is necessary to generate vibrations in the fluid of the inner ear.
  - The vibrations pass along the footplate of the stapes into the oval window which enters into the cochlea.
  

• Structure of the Ear:
  
  

  - The inner ear is a structured fluid-filled cavity within the temporal bone which contains the organs of hearing and balance.
  - It is composed of the osseus labyrinth (bony) which is a convoluted compartment in the petrous temporal bone containing the vestibule (which the oval window opens into) and cochlea;
  and the membranous labyrinth found within the bony labyrinth which is filled with endolymph secreted from the stria vascularis. It consists of the utricle, saccule, semicircular ducts and the cochlear duct.
  

• Structure of the Ear:
  - The foramen rotundum (round window) acts as a pressure equalisation valve which allows vibrations to propagate into the cochlea. The spiral cochlea has a bony core through which it receives innervation. Semicircular canals lie at mutual right angles and are all filled with perilymph.
  - The cochlea has 2 and 3/4 turns and is a blind ended cavity containing 3 tubes: the scala media (cochlear duct) is the central tube which carries the hearing organ that sits on the basilar membrane (a mat of collagen and elastic fibres); and on either side of the scala media lies the scala tympani and scala vestibuli which communicate at the apex of the spiral.
  
  

  - The basilar membrane provides the support membrane for the sensory cells of the inner ear. The organ of Corti contains 4 rows of hair cells, 3 outer (12000 cells) and 1 inner (3500 cells) each supported by pillar cells.

• Structur of the Ear:
  - Hair cells are held erect by phalangeal cells and each have 3 V-shaped rows of stereocilia which are embedded in an acellular, proteinacious mass called the tectorial membrane. 
  
  

  - As the basilar membrane vibrates (moves up and down), these hair cells rub along the tectorial membrane moving it side to sde. The hair cells then become excited and release glutamate onto the dendritic spines of sensory nerve cells. Inner hair cells are the primary sensory cells which form synapses with the fibres of the auditory nerve; outer hair cells are part of a fast motor feedback system that modifies the mechanics of the basilar membrane.

• Sensory Transduction in the Cochlea:
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- The scala media contains endolymph which is rich in potassium (K+ = 140mM, Na+ = 7mM, Cl-= 130mM)
- Whereas the scala vestibuli and tympani contain sodium rich perilymph (K+ = 3mM, Na+ = 150mM, Cl- = 130mM)

• Sensory Transduction in the Cochlea:- Exposure to sound causes travelling waves to run along the basilar membrane. As a result, the stereocilia are deflected by being pushed against the tectorial membrane. This, stretches membranous strands called tip-links (connecting tips of stereocilia in adjacent ranks) which leads to the opening of Potassium channels.
  
  

  - Due to an electrochemical gradient, there is an influx of K+ in the hair cell which depolarises it, causing Calcium ions to enter through the opening of voltage-gated calcium channels. Calcium ions migrate vesicles containing glutamate to the membrane and release it onto the branches of nerve cells, whose cell bodies lie in the spiral ganglion within the bony core of the cochlea.

  - This response saturates movements of 20nm and the minimum degree of movement detected is 0.3nm, which is only slightly greater than most atoms.

Frequency Analysis

• Hair Cells: 
  - The inner and outer hair cells play different roles in sound perception. The single row of inner hair cells is well innervated and is mainly responsible for pitch detection.
  - The 3 outer rows of hair cells, which are poorly innervated, act as the cochlear amplifier. Outer hair cells shorten when depolarised and so their length oscillates in phase with the wave on the basilar membrane. This increases the size of the oscillation of the membrane in the same way that a gymnast can increase the oscillation of a trampoline by jumping in phase with its movement.
  
  

  - We can detect sounds over a wide frequency range, however the vibrations of objects that generate sound do not occur at a single frequency.
  - Superimposed on the lowest frequency are a series of harmonics that are multiples of this lowest frequency. The relative strengths of the harmonics allows us to distinguish sound of the same pitch produced by different instruments or vibrating objects.
  

• Hair Cells:
  - Incoming sound is separated into its frequency compartments by the basilar membrane. Due to its physical characteristics, the highest frequencies travel only a short distance along the membrane, while lower frequencies travel further. This is the principle of tonotopy, pitch is coded by the position on the basilar membrane at which the travelling wave reaches its peak.
   
  - Hair cells at a particular position along the basilar membrane will therefore respond optimally to particular frequencies of sound. This is not the only way in which frequency is coded. At low frequencies (<1000Hz), nerve cells in the auditory system can fire an action potential at the same point (i.e. they are phase locked) on each oscillatory cycle which gives a direct coding of frequency.

  - Between 1000-4000Hz, the nerve cells cannot fire fast enough to mark each cycle, but they remain phase locked. As an average of 30 inner hair cells code each semitone, taken together, the action potentials from this population still codes directly for frequency. Above 4000Hz, the neurones lose their phase locking so that tonotopy is the only indication of frequency.

• Cochlear Implants:- These can be used to restore partially the hearing of individuals whose hair cells have been damaged by high intensity noise/certain drugs, but their nerve cells which are stimulated remain intact.
  
  

  - They operate on the principle of tonotopy. An external microphone receives the sound and it is split electronically into a number of frequency channels (typically about 12).

  - Each channel is used to drive a pair of electrodes, which lie at a different position along a spiral filament inserted into the cochlea. Through the hair cells are inactive, the electrodes stimulate the nerve endings beneath and so if appropriately organised, give the sensation of the pitch that would normally be received from that position on the basilar membrane.

• Stapedius Reflex:- The stapedius muscle attaches to the neck of the stapes and when sound at damaging intensity levels is perceived, it contracts within a few hundred milliseconds to limit the movement of the ossicle chain and so reduces the intensity of the pressure pulses reaching the inner ear.
  
  

  - As it limits the degree of movement of the stapes it is more efficient at blocking low frequencies (large, slow oscillations) than higher ones. It can therefore selectively improve the audibility of higher frequencies against a loud low frequency background. This may be why it is activated automatically just before we speak.

  - The lower frequency components of our own voices are efficiently transmitted through the solid tissues of the neck and skull and so blocking these selectively may not only protect the ear, but also allow it to retain some sensitivity to incoming hgh frequency sounds.

Noise-Induced Hearing Loss:
- Sound intensity is measured in a logarithmic scale of decibels (dB). The level of 0dB is arbitrarily set at the threshold of human hearing and each increase of 20dB represents a tenfold increase in the energy carried by the sound. The occupational limit to sound intensity over an 8 hour day is set at 87dB and with every 3dB increase the allowable length of exposure is halved.
- Exposure to very high sound levels first produces a temporary increase in the hearing threshold which may be accompanied by other disturbances in hearing such as ringing or whistling in the ears, e.g. after attending a loud rock concert. Other symptoms include ear discomfort, sound appears muffled and difficulty interpreting speech.

- Greater exposure to these sound levels can result in permenant deafness and the destruction of hair cells. In mammals, hair cells do not regenerate. The mechanisms of this are not fully understood but it is believed that it is due to free radical formation by metabolic overactivity of mitochondria responding to excessive levels of hair cell activation. This can be accompanied by an excessive increase in intracellular calcium and can be exacerbated by the blood supply to the ear being insufficient to sustain high levels of hair cell metabolism.
- Noise induced hearing loss is often characterised initially by a peak loss of sensitivity at about 4000Hz, which is close to the resonance frequency of the external ear canal.

The auditory system analyses sound frequency and intensity. The organ of Corti can detect the many component frequencies of a complex sound simultaneously. Their relative intensities allows us to identify the nature of sound.
Sound generates travelling waves along the basilar membrane where high freqencies only reach the base, and low frequencies run further towards the end. Complex sounds are separated into their component frequencies equivalent to a Fourier transform.

The entire auditory pathway from the basilar membrane to the cortex, is tonotopically organised, i.e. the relative position of the axon within the pathway provides an orderly representation of the frequencies they code for.

• Ascending Pathways:
  - Hair cells in the organ of Corti synapse onto primary auditory neurones whose cell bodies lie in the spiral ganglion which lies in the core of the cochlea. Ganglion cell axons terminate in cochlear nuclei which project along the lateral lemniscus to the midbrain inferior colliculus.

• Ascending Pathways:
  - Unlike any other sensory modalities, auditory pathways project bilaterally so that information from each ear runs up both sides of the brainstem. This is vital for sound localization which is achieved by detecting the time delay and intensity differences between sound reaching the two ears, and the inferior colliculus contains a map of the auditory space based on these comparisons.
   
  

• - The inferior collicluli project to the medial geniculate body and hence to the primary auditory cortex on the superior surface of the temporal lobe. This contains several tonotopic maps in which different frequencies across the range of hearing are arranged in an orderly spatial array. Plasticity is found in the auditory cortex just as it is elsewhere in the CNS, and it tends to be enlarged in professional musicians who process sound patterns analytically.
  - The secondary auditory cortex includes Wernickes area, which is a centre for the analysis of language and is found in the dominant hemisphere. On the opposite hemisphere, the secondary cortex is responsive to pitch changes in speech and music.
  

• Ascending Pathways:- Identifying single auditory sources requires the recognition that they give rise to a harmonic series of frequencies. The brain attributes to each of these a single pitch, i.e. the single frequency we use to label the harmonic series (lowest harmonic) and these may also be mapped in the auditory regions of the brain.
   
  - If an incomplete harmonic series is presented, in which for example the lower frequencies are missing, the brain can still attribute to it the pitch to which the series belongs, even though that frequency is not present, i.e. we hear a pitch that is not there. This is known as the missing fundamental illusion and is an indication of robustness of pattern recognition mechanisms.

  - Individual cortical columns are tuned to particular frequencies but the sharpness of this tuning may vary greatly between nerve cells. Some columns may be excited by sound from both ears, while in others this causes inhibition.
  - It appears that different aspects of complex patterned sounds are processes in a modular fashion; pitch, melody and rhythm are proessed in different locations. Timbre defines the different vowels.

• Descending Pathways:
  - The sensitivity of hair cells can be controlled by descending feedback from the auditory cortex and the superior olivary nucleus in the medulla oblongata.
  
  

  - Axons project directly to the outer hair cells where they control the cochlear amplifier. Control of the inner hair cells is indirect as the descending axons target the neurones of the spiral ganglion that receive input from the hair cells.

  - These 2 pathways play a role in selective attention and in the suppression of background noise of particular frequencies, and contribute to what is known as the cocktail party effect, which makes it possible to listen to one conversation against the noise of a crowded room.
   
  

• Localization of Sound Sources:
  
  

  - The position of a sound source can be localized with an accuracy of 3-10 degrees in the horizontal plane. This is achieved by comparing information arriving at the 2 ears using two parameters.

• Localization of a Sound Source:
  Interaural Time Delay (ITD) - When the sound is directly in front, it reaches the two ears simultanously, but when it is at 90degrees to this, left or right, the wavefront reaches one ear 0.6ms faster. At intermediate angles the delay is smaller. This delay is detected by neurones in the superior olivary nucleus and can be used to determine sound source position on the horizontal axis. This is only unambiguous if the wavelength of the sound is greater than the distance between the ears.

Interaural Intensity Differences (IID) - For sounds with shorter wavelengths (>1500Hz), the loudness of the sound reaching the two ears is compared. At these frequencies the sound waves do not bend efficiently around the head so a sound shadow is created on the side opposite the sound source. The degree of attenuation of the sound will depend on the angle the source lies.

- Information on sound source position is used to drive auditory reflexes which turn the head and eyes towards the origin of the sound so it can be identified visually. This does not involve the cortex, but is driven by the midbrain inferior colliculus, which is on the ascending auditory pathway. This in turn projects to the visual midbrain, the superior colliculus where the auditory spatial map is superimposed on a visual one. From the colliculi, the tectospinal tract descends to the motor pools for the muscles of the neck which turn the head.

The Vestibular System
The vestibular systems of the ear detect the acceleration of the head in space. Constant velocity cannot be detected, only changes in the velocity. The vestibular system is composed of two part:
1) The saccule and utricle, which lie in the vestibule and monitor linear acceleration;
2) Semicircular canals which monitor angular acceleration.

• Linear Acceleration:
  - The saccule and utricle are fluid-filled spaces within the membranous labyrinth of the vestibule, each containing a patch (macula) of sensory epithelium.
  - This contains an array of hair cells that look simlar to those in the cochlea except that they retain a true cilium (kinocilium) at the head of the ranks of stereocilia.
  - The tips of the hair cells are embedded in a gelatinous protein mass (the otolithic membrane) whose mass is increased by the presence of protein calcite crystals called otoconia.
  - When the head is horizontal and level, the macula of the utricle is also level, while that in the saccule is vertical. When the head is tilted back, the utricular otolithic membrane slumps in the same direction, dragging the stereocilia of the hair cells with it.
  - This generates a signal which represents the acceleration due to gravity acting on the macula. The hair cells in the macula are not orientated at random but are organised along a central axis with the direction of optimal sensitivity facing in opposite directions on each side.

• Angular Acceleration:- This is monitored by the three semicircular canals which lie at right angles to eachother. When information from the canals on the left and right side are integrated, they provide an unambiguous indication of angular acceleration. The hair cells responsible for this are found in the flask-like enlargements (ampullae) that lie at the base of each of the canals.
  
  

  - Within each is a ridge (crista) covered with a sensory epithelium made up of hair cells that are similar to those in the maculae.

  - The surface of the cells are again embedded in a proteinacious gel, which in this case forms a large dome-like structure (cupula) that almost fills the canal. When the head rotates, the movement of the fluid in the canals lags behind during the initial acceleration due to its inertia and to friction with the walls of the canal.

  - This causes the cupula to be deflected, which bends the stereocilia generating a signal.

• Vestibular Pathways:
  - Information from the saccule, utricle and semicircular canals is passed to neurones in the vestibular (Scarpa's) ganglion which project to the vestibular nuclei of the medulla.
  
  

  - These have reciprocal connections with the cerebellum and are part of the extrapyramidal motor system which is involved in movement that are not under conscious control, e.g. postural movements.

  - The vestibular system also controls coordinated neck and eye movements that allow visual fixation to be maintained despite movements of the body.

Humans are microsomatic as we are higher up the food chain. Information from the environment is coded into a smell. The olfactory environment is constantly changing, as any movement will cause 'flurries' of air to change the smell.

• Olfactory Pathway:
  - Information is detected by the olfactory receptor and sent via the olfactory nerve to the olfactory bulb located on the inferior surface of the brain. This then transmits signals to the olfactory cortex to determine the smell.
  - Olfactory receptors are found in olfactory neurones buried in non-motile cilia. Information is sent from these to glomeruli in the olfactory bulb which relay it to the brain.

• What is a Smell?- Most odorants are volatile but they must be water soluble to be able to dissolve in the nasal mucus (secreted by Bowmans glands) and diffuse across to receptors on cilia.
  - This is therefore aided by odorant binding proteins (OBPs) which are 'shuttles' that transport odorants.
  - They also aid in clearance by secreting various metabolic enzymes to remove unwanted substances from the mucus.
  
  
• Olfactory Receptor Neurones (ORNs):- Each ORN has 8-20 non motile cilia which contain the receptor protein. The other end of the ORN has an unmyelinated axon. 10-100 axons form a bundle, and each bundle becomes a primary olfactory nerve fibre.
  - This fibre passes through the cribriform plate and first
  synapses in the olfactory bulb.
  

• Olfactory Receptors:- The gene was first cloned in 1991 by Buck & Axel and it has found to be the largest gene family so far with ~1000 members.
  - Most of them are pseudogenes and only 350 code for functional receptors.
  - The receptors are 7 transmembrane GPCRs with highly variable domains 3-5 and are probably the odorant binding site. The C-terminus and intracellular loops I2 and I3 are G-protein binding domains. Epithelia within cilia have protusions called knobs.
  
  
• Transduction:
  - The odour docks onto the OBP which transports the odorant to the receptor. This activates a G protein from the Golf family which activates adenylyl cyclase to convert ATP to cAMP and thus increase the cAMP concentration.
  - This increase opens cyclic nucleotide gated cation channels to allow Na+ and Ca2+ in to depolarise the cell. Intracellular calcium ions activates a Cl- channel to allow Cl- ions to leave the cell, thus depolarizing it more.
  

• Smell Dysfunction:
  Dysfunctional adenylyl cyclase:
  - No cAMP causes patients to be completely anosmic. They can be treated with a phosphodiesterase inhibitor which prevents the inactivation of AC.
  A loss of the pigment from vitamin A can also lead to anosmia.
  Ciliopathies:
  - Bardet-Biedl Syndrome (BBS) which includes a mutation in the BBS4 gene coding for a protein in the basal body of cilia to cause anosmia in 60% of cases.
   
  
• Theories of Olfactory Transduction:
  - After the initial steps of olfactory transduction, the depolarization will spread up the cilia and the potentials of the all the cilia are summed at the dendritic knob. If threshold is reached, the ORNs fire an action potential up to the olfactory bulb.
  1) Molecular Shape theory: John Amoore (1952) suggests that odorants have different shapes to allow recognition of different smells.
  2) Molecular Resonance theory: Turin (1996) suggests the nose is like a 'spectroscope' using NADPH to supply electrons which can only tunnel through the receptor if an odorant fills the receptor site, and the vibrational energy equals the energy gap. Electrons will then flow through the protein and reduce the disulphide bridge via Zn2+.
  

There is one olfactory receptor neuron for one receptor type. The olfactory bulb and tract are found on the anterior, inferior surface of the brain.
There are 2000 glomeruli (a collection of dendrites of one cell) in a rabbits olfactory bulb, and 25000 olfactory axons per glomerulus. There are 25 apical dendrites of mitral cells which are send to a single spherical glomerulus, plus 45000 mitral cells in each olfactory bulb.

Olfactory receptor neurones send information through the cribriform plate into the olfactory bulb to synapse onto glomeruli, which send dendrites to mitral, periglomerular and tufted cells that transfer information along the olfactory tract. Functionally equivalent ORNs expressing the same receptor go to the same glomeruli.

Glomeruli are molecular feature detectors where a certain odorant can activate a glomeruli strongly whilst affecting others with less efficiency to very little at all. As the axons of the ORNs migrate towards their specific glomeruli they often overshoot into neighbouring glomeruli. Thus, a glomerulus representing a specific OR develops slowly and involved considerable axonal reorganization in order to achieve the highly topographical projection observed in adult mice.

• Olfactory Bulb:
  - The transduction of odorants in the olfactory cilia and the subsequent changes in electrical activity in the olfactory receptor neuron are only the first steps in olfactory information processing. Unlike other primary sensory receptor cells (e.g. photoreceptors in the retina or hair cells in the cochlea), olfactory receptor neurones have axons and these relay odorant information directly to the brain via action potentials. As the axons leave the olfactory epithelium, they coalesce to form a large number of bundles that together make up the olfactory nerve.
  - Each olfactory nerve projects ipsilaterally to the olfactory bulb, which in humans lies on the ventral anterior aspect of the ipsilateral cerebral hemisphere.

  - The most distinctive feature of the olfactory bulb is the array of glomeruli - spherical accumulations of neuropil (100-200um in diameter). Glomeruli lie just beneath the surface of the bulb and are the synaptic target of the primary olfactory axons.
  - In vertebrates, ORN axons make excitatory glutamatergic synapses with the glomeruli. In mammals, including humans, within each glomerulus the axons of the receptor neurones contact apical dendrites of mitral cells, which are the principal projection neurons of the olfactory bulb. The cell bodies of the mitral cells are located in a distinct layer of the olfactory bulb deep within the glomeruli.

• Olfactory Bulb:
  - A mitral cell extends its primary dendrite into a single glomerulus, where the dendrite gives rise to an elaborate tuft of branches onto which the axons of olfactory receptor neurons synapse.
  - Each glomerulus also includes dendritic processes from two other classes of local circuit neurons: approx 50 tufted cells and 25 periglomerular cells contribute to each glomerulus.
  - Granule cells, which constitute the innermost layer of the vertebrate olfactory bulb, synapse primarily on the basal dendrites of mitral cells within the external plexiform layer. They lack an identifiable axon and instead make reciprocal dendrodendritic synapses with mitral cells.
  - Granule cells are thought to establish local lateral inhibitory circuits with mitral cells as well as participating in synaptic plasticity in the olfactory bulb. Olfactory granule cells and periglomerular cells are among the few classes of neurons in the forebrain that can be replaced throughout life in some mammals.
  
  

  - The relationship between olfactory receptor neurons expressing one odorant receptor and small subsets of glomeruli suggests that individual glomeruli respond specifically to distinct odorants.
  - Molecules with different distinct chemical structures (i.e. different functional groups) have different odours and thus maximally activate different glomeruli. There is thus a relationship between chemical composition and the subjective experience of smell.
  

• Olfactory Bulb:
  - Molecules with a carboxyl functional group have a sour odour, with aldehyde group have oily odours, hydroxyl group have a fresh or sweet smell, ketone groups have ethereal smells, amino groups have fishy odours, ester groups have fruity odours.
  
  
• Mapping Glomeruli:Using 2DG, which tags different areas, you can see where different chemical compounds target on the olfactory bulb. Molecules with a shared carboxylic acid functional group overlap in their activation of the anterior clusters, consistent with their shared functional group. In contrast, the posterior activity patterns differed greatly among these odorants.
  
  
• The Olfactory Code:- After complex signalling, information is sent from the olfactory bulb to the primary olfactory cortex.
  - via the lateral olfactory tract information is sent to the limbic system for emotional affect, endocrine response and memory (involuntary response).
  - Orbitofrontal cortex for conscious perception, recognition, initiation of voluntary response.
  

Taste drives appetite and protects us from poisons. Humans have an innate liking for sugary tastes because our bodies have a requirement for carbohydrates. We also have innate cravings for salt because we must have sodium chloride in our diet.

Bitter and sour tastes cause aversive, avoidance reactions because most poisons are bitter and food, as it decays, goes sour (acidic).
We also have an absolute need for protein, and amino acids are the building blocks for protens so the taste quality umami drives our appetite for amino acids in meats and savoury tastes.

There are thus 5 basic tastes: salt, sour, sweet, bitter and umami.
There are 3 papillae found on the tongue: 200 fungiform with 1-18 taste buds each (1120 in total);
5-6 Foliate each side with 117 taste buds each (1280 in total); and 3-13 Circumvallate with 252 taste buds (4600 total).
- There are also 2500 taste buds on the epiglottis, soft palate, laryngeal pharynx and oral pharynx.

In mammals, taste buds are groups of 30-100 individual elongated "neuroepithelial" cells (50-60um in height, 30-70um in width). Often, but not always, embedded in special structure in the surrounding epithelium, termed papillae.
At the apex of the taste bud, microvillar processes protrude through a small opening, the taste pore. Below the taste bud apex, taste cells are joined by tight junctional complexes that prevent gaps between cells.

• Taste Transduction:- The Na+ ions from salted foods open voltage gated sodium channels causing depolarisation of the basolateral membrane. This results in voltage gated calcium channels to open allowing calcium into the cell which migrate vesicles containing neurotransmitter. The transmitter is released across the synapse and bind to receptors on the afferent nerve to increase the firing in this nerve.
  - This is also caused by H+ ions from sour tastes which open voltage gated H+ channels.
  - Sweet, bitter and umami tastes bind to receptors on the apical membrane which are associated with a G protein that, once activated, opens a TRPM5 channel which results in depolarisation and the above mechanism once again occurs. The G protein also activates phospholipase C to hydrolyse PIP2 into DAG and IP3 which both promote calcium release, which migrates the neurotransmitter vesicles to release the transmitter onto the afferent.
  

• Bitter Receptor Family:
  - There are 50-80 members of T2R's which are expressed in a small subset of taste papillae and expressed in cells that also express alpha-gustducin. 70% of gustducin cells are in circumvallate and foliate papillae express T2Rs.
  
  
• Sweet and Umami Receptors:- These are heteromeric receptors made up of a combination of different subunits, coded for by a small gene family of T1R's. (3 genes distantly related to mGluRs).
  - All 3 T1R genes are expressed selectively in human taste receptor cells in the fungiform papillae, consistent with their role in taste perception.
  - T1R1 + T1R3 = the amino acid receptor (umami); T1R2 + T1R3 = the sweet receptor, whereas T1R3 on its own may be the sweetener receptor.
  
  
• Other Tastes:- CD36 is an integral membrane protein on the cell surface which binds fats and has a role in fatty acid metabolism, taste and dietary fat processing in the intestine.
  - Lingual lipase reduces triglycerides, mono and di-glycerides and free fatty acids. FFAs inhibit delayed-rectifying K+ channels in taste cells.
  

• Other Tastes:
  - Astringency is the name for unripe fruit tastes, tannins and oxalic acid. Tannic acid is produced as a defense against insects and activates specific neurones in the brain suggesting it should be considered a separate flavour or taste.
  - Metallic tastes (e.g. Cu2+, FeSO4, or blood in the mouth). Some drugs cause this taste (metronizadole, acetazolamide).
  
  
• Taste Coding:TRCs are tuned to various tastes via 'cross-fibre patterns'.
  - New research shows that sweet, umami, bitter, sour and salt taste cells are segregated into non-overlapping populations expressing distinct receptors, i.e. 'labelled lines'.
  - When knock-out experiments were done: Knockout the gene T1R2 resulted in no sweet sensitivity, and knocking out T2R means no bitter sensitivity and a lack of PKD2L1 meant no sour sensitivity.
  - Work by Roper (2013) has suggested a different approach to labelled lines.
  

• Taste Nerve Pathways:
  The Peripheral pathway
  - Taste receptor cells do not have an axon so information is relaying onto terminals of sensory gustatory fibres by the transmitter ATP.
  - These fibres arise from the ganglion cells of the cranial nerves VII (facial) and IX (glossopharyngeal).
  
  

  The Central Pathway
  - Primary gustatory fibres synapse centrally in the medullary nucleus of the solitary tract. From there, the information is relayed either to the somatosensory cortex for the conscious perception of taste, or to the hypothalamus, amygdala and insula, giving the so-called "affective" component of taste. This is responsible for the behavioural response, e.g. aversion, gastric secretion, feeding behaviour.
  

• Anatomy of the Eye:
  - The eye consists of many different parts including a large vitreous body, a lens, pupil, iris, aqueous humour and cornea. The retina is located on the back of the eye and consists of a macula (within which is a fovea) and optic disk (blind spot).
  
  

  - There are 6 extraocular muscles which control the positioning of the eyeball in its socket which are innervated by the oculogyric nuclei. The oculomotor nerve innervates the inferior oblique whose main function is extorsion, and the superior, medial and inferior rectus muscles which are involved in adduction of the eye. The trochlear nerve innervates the lateral rectus and superior oblique muscles both of which are involved in abduction.

  - The light reflex is controlled by the ciliary ganglion (innervated by the oculomotor nerve) by which in bright light, the circular sphincter muscle of the iris contracts and pupil constriction occurs. In dim light, the radial dilator muscle contracts to widen the pupil.
  

• Focussing and Refractive Errors:
  - The cornea and lens are at the interface between the physical world of light and the neural encoding of the visual pathways. They bring light into focus at the light sensitive receptors in the retina and initiate a series of visual events that result in our visual experience.
  - The initial encoding of light at the retina is the first in a series of visual transformations. The stimulus at the cornea is transformed into an image at the retina but it is an inverted, blurred copy of the input. The lens of the eye brings the image into a higher intensity focus.
  
  

  Accommodation - The ciliary muscle, controlled by the ciliary ganglion and CN III, is attached to the lens of the eye by zonular fibres. When the ciliary muscle contracts, the zonular fibres relax and the len become more spherical to allow the eye to focus on nearby objects.
  - For the eye to focus on objects far away the ciliary muscle relaxes to make the lens less spherical.

  Vergence Eye Movements - Accommodation and convergence are coupled (under brainstem control). If they are abnormal this results in strabismus. To focus on objects far away the eyes diverge, whereas they converge together to focus on objects nearby.
  

- The cornea forms the major part of the refractive power of the eye (70%) and is primarily responsible for the generation of the image on the retina.
- The lens adjusts focal length for near or far objects and forms 30% of the refractive power of the eye. Near focus there is a more spherical lens.
- The near-point is the closest point at which an object can be focussed (~10cm) and as the lens gets stiff with age the near point recedes to greater than 1m.
- The far-point is the farthest point at which an object can be focussed (infinity).

• Focussing Errors:
  - In normal vision the image is focussed on the retina independently of viewing distance. Problems occur when eye shape and focussing power are not matched.
  - In a person with myopia (nearsightedness) their cornea or lens is too powerful or the eyeball is too long, and so the image is focussed in front of the retina. This means that close objects appear clear but far objects are blurred.
  - In a person with hyperopia (farsightedness) their cornea or lens is too weak as their eyeball is too short, so the image is focussed behind the retina. This means that far objects appear clear whereas close objects are blurred.
  - In presbyopia, the lens becomes stiffer and so the near point recedes, which means that far objects appear clear and close objects are blurred.

• Focussing Errors:
  Astigmatism - Points become blurred into lines along the axis of the astigmatism. Caused by different refractive powers for different axes. Cornea has uneven curvature. This results in images being blurred in one direction only.
  Correction: - Concave corrective lens (negative) for myopia; Convex corrective lens (positive) for hyperopia; and for astigmatism = a cylindrical corrective lens instead of spherical.
  
  
• Photoreceptors:
  - Rods and cones have different outer segment shapes for their different functions. Each outer segment contains stacks of membrane disks with visual pigments. Each inner segment is the location of major organelle, metabolic operations such as photopigment synthesis and ATP production. Then there is a synaptic terminal where the cells synapse with bipolar cells. 
  - Rods have isolated discs whilst cones have continuous discs with outer segments.
  
  
• Rhodopsin:- Is a protein with 7 alpha transmembrane helices. In the 7th helix is the attachment site for the retinal molecule adopsin. The extracellular loop between 5 and 6 is the site of interaction with cytoplasmic proteins, and the phosphorylation site is found on the C-terminus.
  - The region containing oligosaccharides is found on the N-terminus.
  

• Retinal Isomerization:
  There is a kinked retinal form bound to opsin known as 11-cis isomer which appears as purple. In the presence of light, energy from absorption straightens the kink to produce an all-trans isomer detatched from opsin which appears colourless.
  
  
• Phototransduction:- In the dark (resting) state, Na+ and Ca2+ ions enter the outer segment of the disc through cyclic nucleotide-gated channels. At this point guanylyl cyclase activity is low. 4 cGMP molecules bind on the cytoplasmic side to CNG channel to keep it open.
  - In the presence of light, the rhodopsin molecule absorbs photons and isomerizes the cis to the trans isomer, changing the shape to meta-II (the activated form R*) in 20us.
  - The activated form binds to transducin to convert GDP into GTP and the activated subunit G* alpha is released. 1 R* yields 500 activated G* alpha molecules per second.
  - Phosphodiesterase is then activated by G*. One G* removes 1 PDE y subunit, but as there are 2 of these subunits then 2 G*'s are needed to give the activated PDE*alphabeta.
  - PDE splices cGMP into ordinary GMP to decrease the concentration of cGMP in the cytoplasm, so it unbinds from the CNG channel to close it. (each PDE* hydrolyzes 200 cGMP per second).
  - 250 CNG channels close due to a single photon caught, and thus 5mill Na+ ions are prevented from entering per second. So 1mV hyperpolarisation occurs at the inner segment.
  

- In the dark there is high [cGMP] and channels are open, whereas in the light there is low [cGMP] and the channels are closed.

Phototransduction causes a decrease of transmitter release. When the cell is hyperpolarised, voltage gated calcium channels are not activated and thus calcium ions do not enter the cell, so the vesicles are not migrated to fuse with the presynaptic membrane etc.

In the recovery phase, retinal recombines with opsin to form rhodopsin again and the retinal is converted to its inactive form.

• Cascade Inactivation:
  1) Phosphorylation of metarhodopsin II (R*) by rhodopsin kinase.
  2) Completion of phosphorylation and stabilising by arrestin (Arr) - causes inactivation of R*.
  3) Inactivatin of the G-protein (transducin) and phosphodiesterase by a GTPase activating protein.
  4) Regeneration of cGMP by guanylyl cyclase depends on low [Ca2+] and requires GTP.
  5) cGMP-gated channels reopen.

• Brightness and Bleaching Adaptation:
  - Brightness (or light) adaptation: The cGMP gated Na+ channels are also permeable for calcium ions in the dark. During illumination, cGMP gated channels close and intracellular calcium ion concentration falls because of the activity of the Na+/Ca2+ pump.
  - Calcium ions no longer inhibit guanylyl cyclase, which recycles cGMP from GTP. cGMP is replaced quickly and cGMP gated channels reopen, keeping the response to light relatively small and brief.
  
  

  - The human visual system functions over >10 orders of magnitude of light intensity. It cannot cover the whole range simultaneously (membrane potentials and spike rates cannot vary that much). Overall intensity discrimination is broad because a different set of incremental changes can be detected at each new adaptation level.
  - Subjective brightness (i.e. perceived intensity) is a logarithmic function of light intensity differences incident on the eye. The smallest detectable change in birghtness increases in proportion with the background level of illumination (Webers law).
  - Sensitivity is adapted to the ambient brightness level.
  

Cone response is adapted to different ambient light levels.

• Bleaching (or dark) Adaptation:
  - Depends not on light intensity but on how much pigment was bleached.
  - Lasts a lot longer than brightness adaptation (up to half an hour).
  - Recovery time corresponds to time required for pigment to regenerate.
  - Prolonged darkness results in regeneration of bleached photopigment and restoration of retinal sensitivity.
  Regeneration of Rhodopsin After Full Bleach - Wald cycle: R* decays into all-trans retinal and opsin; Enzymatic re-isomerization of 11-cis retinal in retinal pigment epithelium; Recombination of retinal and opsin to rhodopsin.
• Visual Acuity:
  - Visual resolution is a measure of the fidelity with which the visual system can transmit fine detail of the visual world. Acuity is the ability to resolve 2 separate points.
  - Limiting factors include quality of the optics (sharpness of image), and density of the retinal receptors (grain).

• Visual Acuity:
  - Spherical and chromatic aberration.
  - A large aperture (i.e. widened pupil) means more light rays come through the periphery so there is more aberration (blur). With a small aperture there is minimized aberration, increased depth of focus and the refractive index increases with decreasing wavelength.
  
  

  Limits of Visual Resolution
  - In order to minimize spherical aberration, the pupil size should be reduced as much as possible. However this results in less light on the retina, and thus "diffraction blur" caused by the aperture edge being proportional to wavelength/aperture.
  - In the dark diffraction is smaller but spherical aberration is worse. The optimal pupil size is ~3mm.
  - The smallest detail in the retinal image that the optics will allow to resolve is well matched to the photoreceptor array.

  - Photoreceptor density decreases towards the periphery, and cone density peaks in the fovea and falls off rapidly. Whereas, rod density peaks at ~18o eccentricity. Acuity declines with receptor density.
  

• Visual Acuity:
  - The rod system has poorer visual acuity than the cone system. This is because in rods there is wide spacing and integration over a large area of retina, so there is large convergence to one ganglion cell.
  - Whereas, in cones which are tight spacing together, there is integration over a small area of the retina so there is a small convergence to one ganglion cell and thus there is higher acuity.
  - Acuity decreases from the centre to the periphery (from cones to rods).
  
  
• Comparison of Rods and Cones:Cones - Mediate photopic vision; Day-time light levels; Range of colours (trichromatic); Cones are densest in the fovea; Cone density falls off sharply in the periphery; Low sensitivity to light; Quick recovery in the dark.
  Rods - Mediate scotopic vision; Low (moon) light levels; Shades of grey; No rods at the fovea; Rod density rises in near periphery; High sensitivity to light; Slow recovery in the dark.
  

• Retinal Circuitry and Receptive Fields:
  Anatomy of the Retina - Found at the rear of the eye, there is a layer of sclera, then a choroid layer containing blood vessels, then a pigment epithelium which absorbs excess light.
  - Then further into the eye you would find the neural cells of the retina, where axons will exit via the optic nerve.
  - Light is absorbed by the pigment epithelium and signals are sent from cone or rod cells, in the outer segment of the retina, to integrate information into bipolar cells (found running from the outer plexiform layer, through the inner nuclear layer to the inner plexiform layer) which then transmits this information to the ganglion cells (found in the ganglion cell layer) which innervate the optic nerve in the optic fibre layer.
  
  

  Receptive Fields - The receptive field is the area on the receptor surface where an appropriate stimulus causes a change in neuronal activity. In the visual system, it is the region on the retina where illumination influences a cell's response.
  - Nowadays the term tends to include a description of the substructure, not just a demarcation of its boundaries.
  

• Ganglion Cell Receptive Fields:
  - Receptive field centres vary markedly and systematically in size, being smallest in the fovea. In the monkey, the smallest RF centres measured are 2 min arc or 10um on the retina, while cones in the fovea have a diameter of 2.5um, a figure that matches well with our visual acuity: we are able to discriminate two points as close as 1 min arc.
  
  

  - Cone cells activate flat bipolar cells and inhibit invaginating bipolar cells which have different types of glutamate receptors; and also innervates horizontal cells which provide lateral inhibition and feedback to inhibit the cone cells.

• Lateral Inhibition and Centre-Surround Antagonism:
  - Lateral inhibition creates centre-surround receptive fields. A bipolar cell receives direct excitatory input from the photoreceptors at the centre and indirect inhibitory input from those in the surrounding.
  - Lateral inhibition allows us to detect edges of objects better.
  - It can be used to explain the perception of Mach bands where our perceived brightness is higher than the actual illumination.
  - Also the hermann grid, in which we see grey spots in a white space surrounded by black squares because of the detection of those black edges.

• Colour Vision:
  - Perceiving colour allows humans and many other animals to discriminate objects on the basis of the distribution of the wavelengths of light that they reflect to the eye. The light visible to the human eye occupies a tiny part of the electro-magnetic spectrum, falling between the infrared and ultraviolet reigons. The visible light wavelength range is 380-750nm.
  
  

  Trichromatic Theory - Unlike rods, which contain a single photopigment, the three types of cone cells differ in the photopigment that they contain. Each photopigment is differentially sensitive to light of different wavelengths, and for this reason cones are referred to as blue (short, 437nm), green (medium, 533nm) and red (long, 584nm). Individual cone cells are entirely colour blind and are not excited by these wavelengths of light, but their response is in the reflection of the number of photons that they capture. The perceived colour is the overall pattern of cone stimulation, i.e. the ratio of responses of the 3 cone types.

  Opponent Process Theory - Is a competing theory proposed by Hering (1878) in which there are 2 classes of processes: 1) Spectrally opponent; 2) Spectrally non-opponent. When you match the primary colours yellow, blue, red and green with antagonistic centre-surround receptive field organization: Red-Green (majority); Blue-Yellow (minority); Black-White (luminance detection). Each colour response can be on or off.
  - Both theories are correct at different levels of visual processing.
  

• Colour Vision Anomalies:
  - There are various forms of "colour blindness" which 8% of caucasian males suffer from and only 0.5% of females.
  - Achromatopsia is when someone has no colour vision at all. They could have only rod monochromats and completely lack in cone cells, which is associated with reduced visual acuity, hypersensitivity to light (photophobia) and other vision impairments. However, they could have cone monochromats and have only one cone type, where they usually have good visual acuity and none of the other vision impairments found in rod monochromats. This is very rare.
  
  

  Colour Vision Genes - The gene for the blue cone pigments is located on chromosome 7, the genes for the red opsin and green opsin are located on the X chromosome. As womens have 2 copies of the X chromosome and men only have one, it is more likely for men to be colour blind.

  - Dichromacy refers to the loss of one cone pigment, i.e. protanopia (loss of long wavelength pigment); deuteranopia (lacking medium); trianopia (lacking short).
  - Anomalous trichromacyrefers to a change in the absorption spectrum of long or medium wavelength pigments. Protanomoly is dysfunctional L cones affecting 1% of men and 0.02% of women; and deuteranomaly is dynfunctional M affecting 5% of men and 0.4% of women.
  

• Colour Vision:
  Genetics of Anomalies
  - Recombinations (unequal cross overs between homologous chromosomes during meiosis) can change the number of L or M opsin genes, or generate hybrid genes.
  In Humans vs Cats - Humans have a trichromatic view and cats have a dichromatic view with weak blue-green sensitivity and a monochromatic view.
  
  
• Central Visual Pathways and Visual Fields:
  Primary Visual Pathway - Information from the left visual field is detected by the right side of the retina of both eyes. Information from both eyes travels along the optic nerve, down the optic tract and crosses the optic chiasm to synapse in the right-hand lateral geniculate nucleus of the thalamus. Then this is transmitted across the optic radiation to terminate in the primary visual cortex (V1). Information from the right visual field is detected by the left side of the retina and travels the same pathway but on the left side of the brain etc to synapse in V1 also.
  - Aside from this pathway, a second major target of ganglion cell axons is a collection of neurons that lies between the thalamus and the midbrain in a region known as the pretectum. This area is responsible as the coordinating centre for the pupillary light reflex. Pretectal neurons project to the Edinger-Westphal nucleus of CN III which project to the ciliary ganglion
  

• Retinotopic Representation of the Visual Field:
  - Each eye sees a part of visual space that defines its visual field. For descriptive purposes, each retina and its corresponding visual field are divided into quadrants. In this scheme, vertical and horizontal lines that intersect at the centre of the fovea subdivide the surface of the retina.
  - The vertical line divides the retina into nasal and temporal divisions, and the horizontal line divides the retina into superior and inferior divisions. Corresponding vertical and horizontal lines in the visual space intersect at the point of fixation and define the quadrants. The crossing of light rays diverging from different points on an object at the pupil causes the images of objects in the visual field to be inverted and left-right reverse on the retinal surface.
  - As a result, objects in the temporal part of the visual field are seen by the nasal part of the retina and objects in the superior part are seen by the inferior part of the retina.
  
  
• Lesions of the Visual Pathway:- The locus of the lesion determines the nature of the deficit. In the optic nerve it can cause patients to go blind in the ipsilateral eye, monocular vision and limited ipsilateral peripheral visual field loss. In the optic chiasm it causes bitemporal hemianopia, blindness in the nasal hemiretina in each eye, and no peripheral vision. In the optic tract it causes homonymous hemianopia and blindness in the contralateral visual field.

• Lateral Geniculate Nucleus:
  - Consists of 6 layers in humans, receives inputs from both eyes and contains a retinotopic map. Each layer receives input from only one eye. Layers 1, 4 and 6 receive from the contralateral eye; Layers 2, 3 and 5 receive from the ipsilateral eye. Layers 1 and 2 are magnocellular, and layers 3-6 are parvocellular.
  
  
• The Primary Visual Cortex:
  -  The visual cortex is a sheet of neurons ~2mm thick that exhibits a conspicuous laminar structure in preparations stained to reveal the density and size of neuronal cell bodies. V1 is divided into 6 cellular layers which can be further subdivided using latin and greek lettering.
  - It receives inputs from both eyes and the lateral geniculate nucleus axons terminate primarily in cortical layer 4C. These inputs segregate into ocular dominance columns, and cells outside layer 4 are mostly binocular. Orientation selectivity neurones are also found in each layer of V1 except 4C.

• Primary Visual Cortex:
  - Some binocular neurons in the striate cortex and in other visual cortical areas have receptive field properties that make them good candidates for extracting information about binocular disparity. In these neurons, the receptive fields driven by the left and right eyes are slightly offset either in their position in visual space or in their internal organization so that the cell is maximally activated by stimuli that fall on non-corresponding parts of the retinas.
  - Some of these neurons (far cells) discharge to retinal disparities that arise from points beyond the plane of fixation, while others (near cells) respond to retinal disparities that arise from points in front of the plane of fixation. A third class of neurons (tuned zero) respond selectively to points that lie on the plane of fixation. The relative activity in these different neurons is thought to mediate the sensations of stereoscopic depth.
  
  

  - The magno and parvocellular layers of the LGN receives inputs from distinct populations of ganglion cells that exhibit corresponding differences in cell size. M ganglion cells that terminate in the magnocellular layers have larger cell bodies, more extensive dendritic fields and larger-diameter axons than the P cells that terminate in the parvocellular layers.
  - Magnocellular axons terminate in the upper part of 4C (4Ca) while parvocellular axons terminate in the lower part of layer 4C (4Cb).
  

• Visual Areas and Pathways Beyond V1:
  - Anatomical and electrophysiological studies in monkeys have led to the discovery of a multitude of areas in the occipital, parietal and temporal lobes that are involved in processing visual information.
  - Cytochrome oxidase is found in the mitochondria and is active when metabolism is high. It is used to label the functional compartments in V1 and V2, for example to show the "blobs" and interblobs in layers 2/3 of the primary visual cortex, and the thick and thin and interstripes of V2.
  - The thin and pale stripes of V2 project along the ventral stream and the thick stripes project along the dorsal stream.
  
  

  Illusory Contours - e.g. in Kanizsas triangle, cells in V2 respond when 'nothing' sweeps over their receptive fields. Or when there is a coloured box on a coloured background, it matters to the cell whether white is the foreground and grey is the background, so the cell responds differently when it is in a different context.

  Processing Streams: - Each visual area contains a map of visual space and is largely dependent on the primary visual cortex for its activation. There are two visual streams, the dorsal stream running from V1 to V2 in the thick stripe region where neurons will project to V5 (middle temporal, MT, area) for the perception of motion.
  

- The ventral stream runs from the blob region of V1 into the thin stripe region of V2 and then projects to V4 found in the inferotemporal lobe of the brain for the perception of colour, and communicating with V3 to perceive dynamic form. This is therefore known as the 'what' stream.

• V3:
  - The limited evidence suggests that V3 plays a role similar to V2, in that it projects to higher-order visual areas of both the dorsal and ventral streams, and these projections arise from bands or stripes that may segregate projections into parallel processing streams. Consistent with this, single unit recordings in macaque V3d have revealed a fair number of cells selective for colour (20-26%) and/or direction (40%) and a single study recording from V3v found a higher percentage of colour selective (60%) and a smaller proportion of direction-selective (13%) cells.
  - More recent functional data obtained through fMRI in macaques by Wade et al (2008)show that V3 (both dorsal and ventral divisions) is far less responsive to chromatic contrast than V2 and ventral stream area V4, further supporting the idea that V3d and V3v are similar functionally, and suggestive of V3 playing a lesser role in the ventral stream.

• Full Stream Pathways:
  Dorsal - Magnocellular cells of the LGN project to layer 4Ca of V1 which then projects either to the thick stripes of V2 which will project to MT, or it directy projects to MT. MT can then interact with V4, VIP and also MST. MST and VIP are interconnected, and MST also connects to LIP and these two project further to 7a in the parietal cortex.
  
  

  Ventral - Parvocellular cells of the LGN project to layer 4Cb of V1 which then projects to the blobs and interblobs in layers 2 and 3 of V1. From here, projections are sent to the interstripes and thin stripes of V2 which transmit information to V4. This can either directly project to CIT, or can act via PIT to activate it. CIT then projects to AIT in the inferotemporal cortex.

• V5/MT:- Contains neurons that respond selectively to the direction of a moving edge without regard to its colour, i.e. they are sensitive to the motion of an entire object. It responds to bars of light and gratings, and is organised into direction preference columns.
  - It is important for stereopsis (independent of form) as objects in front or behind of the plane that you fixate upon have different disparities, and V5 neurons respond to that.
  

• Lateral Intraparietal Area (LIP):
  - Shadlen & Newsome (2001) studied neurons in LIP that exhibited spatially selective persistent activity during delayed saccadic eye movement tasks. These neurons are thought to carry high level signals appropriate for identifying salient visual targets and for guiding saccadic eye movements. We arranged the motion discrimination task so that one of the choice targets was in the LIP neuron's response field (RF) while the other target was positioned well away from the RF. During motion viewing, neurons in the LIP altered their firing rate in a manner that predicted the saccadic eye movement that the monkey would make at the end of the trial. The activity thus predicted the monkeys judgement of motion direction.
  
• V4:- In this region, neurons respond to non-Cartesian gratings and their response is modified by selective attention. In an experiment, monkeys were trained to look at a fixation point on a screen. The receptive field of a V4 cell was located. On any given trial the fixation point was either red or green, and then six other stimuli came on, one of which fell into the receptive field of the cell. The monkey knew from prior training that it would be required to discriminate only those stimuli that were the same colour as the fixation point, i.e. from three red stimuli in the top row or three green in the bottom row. In the last phase of a trial, only 2 stimuli remain on and the monkey, in order to obtain a reward, must indicate whether the matched stimulus is tilted to the right or to the left.

- Increased response to the same visual stimulus falling on the receptive field of a V4 cell during the match as opposed to the nonmatch trials. Each line represents a successive trial and each dot indicates the discharge of the neuron.

- Like V1, V4 is tuned for orientation, spatial frequency, and colour. Unlike V1, V4 is tuned for object features of intermediate complexity like simple geometric shapes, although no one has developed a full parametric description of the tuning space for V4.
- V4 contains modules known as 'globs' which are organized into clusters in terms of colour preference. Neurons in adjacent glob cells have a similar colour tuning to those nearby and are arranged spatially within the cortex. Inbetween these are 'interglob' areas that are not colour sensitive but respond to shape. They are the first part of the brain in which colour is processed in terms of the full range of hues found in colour space.

• Inferior Temporal Cortex:
  - IT responds to colour and form. The average responses for a single neuron to stimuli with circular shapes is highest than for crosses which is lowest.
  - The response to an object can be represented by the distributed activation of neurons.
  - An IT cell responds strongly to the face of a monkey toy and the critical feature was determined as a configuration in which 2 black spots and 1 horizontal black bar were arranged in a grey disk. The circular outline was essential.

• Recognition of Faces and Places:
  - The Fusiform Face Area (FFA) is found in the fusiform gyrus of the inferotemporal lobe and is responsible for the recognition of faces. It is thus part of the ventral stream in the perception of form and objects as they are in space.
  - Lying lateral to the FFA is the Parahippocampal Place Area (PPA) which is involved in memory encoding and retrieval, but also in the recognition of places and environmental scenes.
  
  

  - It was found by Tong et al (1998) in a study of binocular rivalry, that when an image of a house and an image of someones face were transitioned and presented simutaneously as one image, the neuronal activity in the FFA would increase as the perceptual dominance focused on the face, and the neuronal activity in the PPA would increase as the perceptual dominance focused on the house instead.