Neuro 3 - special senses Flashcards
Auditory system qualities
Mechanical to electrical transduction
Very rapid, works at extremes of physiology
Very small movements transduced
- 70% of over 60s have hearing impairment
- 840 babies born each year with bilateral impairment
What is sound?
Noise generated, then compress and rarefy air as sound wave
Amplitude (peak to trough distance) - loudness - decibels - Db
Frequency (no. of cycles passing point in time) - pitch - Hertz - Hz
But sound is very complex, use Fourier analysis to study tones in a complex sound
- peripheral auditory system is doing this, breaking down complex sounds and encoding to nervous system
Audiometric curve of human hearing
Total area inside curve = area of auditory perception, around 20Hz - 20kHz, 0Db - 120Db
Bottom line = threshold for hearing, lowest intensity (differs at different frequencies)
Top line = level of feeling and pain, sounds too intense and damaging to auditory system
Conversation area in middle, so speak at the most sensitive frequencies
Anatomy of human ear
OUTER - pinna, to funnel sound along external auditory canal
(divided by tympanic membrane)
MIDDLE - ossicles, eustachian tube
INNER - cochlea coil, vestibular system
Outer + middle = conductive part
Inner = sensory-neural part, for transduction
Function of middle ear
Impedence matching:
- airwaves cause tympanic membrane to vibrate
- lever action of ossicle (moving through air)
- stapes moves against oval window, to move fluid
More energy needed to move fluid than air
Hence why oval window very small, energy concentrated to very small area, so 20x increase in pressure
- necessary to move fluid, otherwise not much energy would transfer
Ossicular reflex in middle ear
To protect against intense sounds (= attenuation reflex), reduce damage to ear
2 muscles, stapedius and tensor tympani are attached to ossicles and the bony part of ear
- if muscles tense, bones can’t move freely, stiffens lever action, so decreases energy conduction
BUT
- must be continuous loud sounds, ineffective for impulse noise
- doesn’t work at very high frequency sounds - though can help discrimination of low, so can understand high pitch
Cochlea spiral structure
35mm long when uncoiled
Structure formed by 10 weeks gestation, functional by 20 weeks
Compartmentalised into series of chambers
Chambers of cochlea
Three chambers in a section:
Scala vestibuli + scala tympani - perilymph
Scala media - endolymph, + organs of hearing
Compartmentalisation is essential to keep fluid apart
Scala media contents
Stria vascularis – maintains ion composition of fluid (Na+/K+)
Tectorial membrane – gelatinous membrane overlying organ of Corti
Organ of Corti:
- on flexible basilar membrane
- inner and outer sensory hair cells
- spiral ganglion nerve cells
- associated supporting, non-sensory cells to hold hairs rigidly
Cochlear fluids
PERILYMPH - in scala vestibuli and scala tympani - resembles CSF - to bathe cell bodies of organ of Corti - 0mV potential ENDOLYMPH - in scala media - resembled intracellular fluid - sealed in tight compartment - to bathe surface of organ of Corti - maintained by stria vascularis - +80mV potential
Properties of inner and outer hair cells
Stereocilia (hair-like) projecting from apical surface
Mechano to electrical transduction
Transduction channels in hair bundles
Outward K+ channels in basolateral membrane
Sensitive to damage and disease
Properties of inner hair cells
~3500, one row Flask shaped Hair bundle flat Afferent innervation mainly 10-20 afferent terminals per cell Inward Ca2+ channels
Properties of outer hair cells
~1200, three rows
Columnar shape
Hair bundle in V or W shape
Mainly efferent innervation
(small afferent – one neurone to many cells)
Prestin motor protein in lateral membranes
When sound enters the ear…
Along external auditory canal Vibrates tympanic membrane Moves ossicles in lever action Stapes displaces fluid in scala vestibuli Travelling wave Displace basilar membrane up and down Sensory hair cells contact tectorial membrane, so stereocilia displace membrane -> Travelling wave
Stereocilia response to movement
Arranged in rows, with tallest at back
Tip links between ends of tall and short stereocilia
Movement of the cilia opens ion channels, so K+ rush in – driving force for K+ from endolymph into cell 135mV
- sensitive to very small movements
⇒ depolarisation of hair cell
Voltage gated Ca2+ open, Ca2+ in
Neurotransmitter release, increased firing of nerve cell
After stimulus gone, return to upright position
Phase locking
At rest – some trickle of transducer current (K+ movement)
Positive stimulus – push towards tallest cilia - increase current up to a maximum point
Negative stimulus – push towards smallest cilia – switch off current
Activity in hair cell -> receptor potential -> nerve activity
- only encodes 1-4kHz, we can hear up to 20, so other mechanism also
Tonotropy
For hearing 4+ kHz
Maximum displacement of basilar membrane occurs at different positions – regional variations in fibrous structure
Depends on frequency of sound
In low freq – displacement close to apex
In high freq – displacement close to base of basilar membrane
Tonotopic map in brain so can understand, auditory nerves end at different points on cochlear nucleus (isofrequency bands)
PASSIVE MECHANISM
OHCs role in hearing
Cochlear amplifier - amplification and tuning of IHC stimuli
Tonotopy is passive
Must be active component, otherwise would dissipate and lose energy by end of basilar membrane
Only occurs in live cochlea, by OHCs
- drugs can reduce this
How do OHCs amplify
Depolarisation -> activates prestin (motor protein) -> cells shorten rapidly
Rigidly held cells contract, so amplify basilar membrane movements
Gain (size change) modulated by efferent system
Otoacoustic emissions
Sounds produced by ear
Send click sound in, hear click back
Neural encoding of loudness in IHCs
Louder sounds, larger stimulus
IHCs have numerous (10-20) synaptic contacts with different nerve types:
High spontaneous rate fibres – easily excited at low sound levels, soon saturated
Medium spontaneous rate fibres – excited at medium sound levels, will saturate
Low spontaneous rate fibres – not excited until sound loud, saturate slowly – good for detecting changes in sound at very high sound levels
- sound encoded by activation of populations of neurones
Cochlea to brain main pathway
Cell bodies of afferent nerve terminals in spiral ganglion
Ventral cochlear nucleus
Superior olive – ipsi + contralateral input from both ears, important for localisation of sound. Then carried parallel bilaterally.
Inferior colliculus
Medial geniculate nucleus
Auditory cortex
Function of vestibular system
Report on position and movement of head
Give sense of balance and equilibrium
Coordination and posture adjustment, with cerebellum
- disorders – feels like vertigo - nausea, disequilibrium, nystagmus
Anatomy of vestibular labyrinth
Three semicircular canals – crista
- sensitive to head rotation and angular acceleration
- have sensory hair cells
Otolithic organs – saccule and utricle
- sensitive to gravity, linear acceleration
- have sensory hair cells
Hair cells the same, though for different functions, due to structures they sit in
Vestibular hair cells
Kinocilium are tallest cilia
Type I and II
Afferent and efferent innervation
Transduction similar to IHCs
Transduction and encoding in vestibular hair cells
Positive direction – towards tallest (kinocilium) – depolarisation – excitation
Negative direction – away from kinocilium – hyperpolarisation – inhibition
But, high resting rate of nerve fibres, firing even when hairs vertical, so high sensitivity to direction
Stimulation of macula
Macula = sensory epithelium of the otolithic organs
- saccule and utricle
Otoliths are crystals of calcium carbonate, lie over:
Gelatinous cap, coating hair cells
When head moves, otoliths (high density) lean
Moves gelatinous cap
Deflects stereocilia
Transduction
Positive direction is head to chest
Negative is head back
Hair cell orientation in vestibular apparatus
Many hair cells oriented in different directions:
Saccule and utricle have positive direction facing outwards and inwards respectively
- and organ is curved, so get wide range, have all cell orientations necessary
Semicircular canals also are at 90degrees to each other, so can respond to rotation in any given direction
- hair cells oriented one way in each ampulla
- adaptation after 15-30s as fluid catches up
Peripheral vestibular pathologies
Kinetosis (motion sickness)
Lesions/irritations – usually unilateral
Meniere’s disease – excessive fluid pressure
Benign paroxysmal positional vertigo – otoliths dislodged from utricle
When chronic, can compensate using visual stimuli, proprioceptors
Hearing loss
MILD – difficulty following speech in noisy situations, 25-39dB quietest sounds heard
MODERATE – difficulty following speech without hearing aid, 40-69dB quietest sounds heard
SEVERE – rely on lipreading, even with hearing aid, 70-94dB quietest sounds heard, signing maybe preferred language
PROFOUND – 95dB+ only, signing or lipreading
- conductive hearing loss (damage/blockage to outer or middle ear) or sensorineural hearing loss (damage/loss of sensory hair cells or neurones)
Conductive hearing loss
Damage/blockage to outer or middle ear
Outer – obstructions (eg wax), tympanic membrane rupture (from infection, foreign object, barotrauma)
Middle – otosclerosis (overgrowth of stapes so not proper lever action), glue ear (chronic fluid build up), otitis media (acute inflammation, redness, pain)
Sensorineural hearing defects causes
- drug induced
- genetic defects
- acoustic trauma to hair cells and neurones, acute and chronic
- presbycusis - age related
- infectious disease
- tinnitus
Drug induced sensorineural hearing loss
eg Aminoglycoside antibiotics
- ototoxic, so only used when necessary
LOSS OF OHCS
- dose dependent
- > partial deafness, poor frequency discrimination
- hearing aid helps intensity only, as lost cochlear amplification and tuning
progresses to… (with higher dose/longer treatment)
LOSS OF IHCS AND OHCS
- complete deafness
- need cochlear implant
Acoustic trauma -> hair cell defects
If mild, up to 90dB
- disruption of hair bundle, breakage of tip links
- may be reparable
- temporary threshold shift, eg after club night
Severe, more than 130dB (or quieter but sustained)
- complete loss of area of hair cells
- scar formation fills void
Due to:
- metabolic exhaustion
- physical disruption of hair bundle
- excitotoxicity, damage at synapse
- build up of toxic metabolites
- hole in reticular lamina
Genetic hearing loss
-> most childhood deafness
also -> predisposition to traumatic, ototoxic, age-related hearing loss
- K⁺ channels, for repolarizing hair cell
- Structural components in stereocilia and tiplinks
- Collagens and connexins in connective molecules
Presbycusis
Deafness of ageing
70% of 70+ yos
Starts in high frequencies, loss of hair cells at base of cochlear coil, progresses to lower frequencies with age
Hearing aid to treat
Increased by exposure to:
- drugs
- age
- noise
- genetic predisposition
Tinnitus
Auditory perception without sound stimulus
10-15% adults
Hearing loss main risk factor
Often not originating in cochlear, can cut cochlea nerve and still experience
Less activity in cochlear nerve downregulates inhibitory processes in cortex
No effective drug therapy
Sound therapy and cognitive behaviour therapy
Cochlear implant
Only treatment for severe/profound hearing loss
External speech processor captures sound, converts to digital signals
Sent to internal implant
Implant converts to electrical energy, send to array inside cochlea
Electrodes stimulate auditory nerve - bypass damaged hair cells
Brain hears sound, frequency coding stimulates spiral ganglion neurones in correct position
Candidacy for cochlear implant
EITHER
Postlingually deafened adults
OR
Prelingually/congenitally deaf children
Only in bilateral severe or profound deafness
Need residual neurones - must be put in fast, or neurones connecting to dead hair cells will die
Need normal inner ear anatomy to allow surgery
Auditory cortex not fully developed until age 6, so implant before then
Properties of light
Visible light only narrow band of electromagnetic radiation
- higher wave energy - blue
- lower wave energy - red
Only know colours because of perception, interpretations different
Travels in straight line in vacuum
We see waves, reflected and scattered from objects
Anatomy of eye
Extraocular muscles - to move eyeball in bony orbits of skull
- oculomotor
- trochlear - superior oblique
- abducens - lateral rectus
Pupil - allows light into eye
Iris - muscles to control size of pupil
Lens - curved structure, parasympathetic of oculomotor (ciliary ganglion) control shape
Incident light
Choroid layer - vascular layer with connective tissue
- between retina and sclera
- dark melanin choroid pigment absorbs stray light, limits uncontrolled reflection -> crisp image
- in night animals (reflective eyes), melanin partly absent, have tapetum lucidum to collect as much light as possible, but with less visual acuity.
Retinal landmarks
Optic disk - blind spot
- axons of ganglion to optic nerve
Fovea - depression directly behind pupil - to allow clear path for light to photoreceptors
Macula - yellow disk around fovea
- greatest visual acuity - look straight better than periphery
Foveola - centre of fovea
- contains only cone receptors
Image on retina
Light bends at cornea and lens to form crisp image on back of retina
-> image flipped 180^, back to front and upside down - inverted
Info leaves retina in optic nerve
- some crossing over
- nasal and temporal retina of each eye on same side, forms optic tract
Nasal info crosses, temporal info stays same side
Retinal disease
Macula degeneration - lose central vision, maintain peripheral - problem in targeting image
- mainly in older age
Retinitis pigmentosa - degeneration in periphery - tunnel vision
- heritable
- > night vision and peripheral vision problems
Aqueous humour
To nourish lens, iris, cornea - have no blood supply
Replaced every hour
Produced in posterior chamber by ciliary process
Excess production -> glaucoma, pressure to damage structures
- treat with carbonic anhydrase inhibitor
Pupillary light reflex
Undilated pupil - focus most light into fovea
DIlated pupil - light across retina
(also dilate in response to eg fear)
Direct and consensual reflex - direct for same eye, consensual for other also
- as info from pre-tectal area splits, to Edinger-Westphal on other side
Light enters eye, pupillary reflex
Info along optic nerve
To pre-tectal area (split, also to other side)
To Edinger Westphal nucleus
Info back down pathway on occulomotor nerve via ciliary ganglion, synapse
Short ciliary fibres -> pupillary constriction
Lens
Transparent, bioconvex
Behind iris
Held by suspensory ligaments
Thickens throughout life
In cataracts - lens becomes opaque, accumulation of metabolic products
Accomodation reflex
Ability to look at close objects, switch from far
- ciliary muscles contract - reduce pressure on fibres suspending lens, allows to become convex
- increase refractive power, direct onto retina
Also need convergence:
- need image on fovea of both eyes
- if not, diplopia, double vision
Also need pupillary reflex:
- constrict pupil size, improve focus of light so not scattered - reduces abberation, increased depth of focus
Photoreceptors
Two types, specialised to function - rods and cones, inner segments same
- light sensitive part is outer segment
- light needs to pass through retina before detection
- not barrier to light as retina is transparent and thin
LIght for VISION, not circadian rhythms
Rod photoreceptors
For low levels of light - scotopic
Don’t detect colour
Can detect single photon of light (but won’t percieve light here)
Easily saturated
Discs in outer segment, organised to capture photons
Mostly in periphery - none in foveola
Convergence - info from many rods comes together in CNS - less acuity as from number of receptors
Cone photoreceptors
High levels light - photopic Less easily saturated Mostly in fovea Little convergence - need precise info - single cone to single ganglion cell No discs, membrane folds
3 types - blue (short wavelength), green (medium), red (long)
To detect especially at specific wavelengths (can alos detect at others, overlap to allow brain to create spectrum)
- no blue cones in foveola!
Adaptation to light
Dark to light - quickly adjust (light adaptation)
Light to dark - slowly adjust (dark adaptation), as rods previously saturated, unable to respond until have regenerated photopigment
- pupillary reflex to reduce/increase amount of light in
- changes in conc of visual pigment
- changes in numbers of available light activated channels (Ca2+ conc)
Visual pigments
Rods - rhodopsin (similar to vitamin A)
Cones - iodopsin
Inside discs
From dark to light - conformational change in structure of pigment
Colour-deficient vision
9% males, 0.5% females
- due to absence of a cone type - usually green (deuteranopia) or red (protanopia)
- if blue, rare (tritanopia)
Sex linked recessive, on X chromosome (so more common in men)
Ishihara plates to test
Colour should be constant for everyone - weird dress is photo taken in fluorescent lighting, brain not adapted to understand - PERCEPTION
Photoreceptors transducing stimulus
Photopigment sits in membrane
Coupled to G protein
DARK
Pigment in cis form
G protein inactive
Ion channels open, as coupled to cGMP, mainly Na+ enters cell = DARK CURRENT
-> photoreceptor depolarised (-30mV) - glutamate continuously released, bipolar cell inhibited
LIGHT Pigment activated, conformational change G protein activated Removal of cGMP from ion channel Ion channel shuts, no +ve ions in -> cell hyperpolarised (-60mV) - no glutamate release, bipolar cell can transmit signal
Light adaptation
Ca2+ enters in dark also - levels higher than others
Inhibits cGMP synthesis
Long term light, Ca2+ levels fall, some synthesis cGMP allowed
Some dark current flow
Can re-respond
- why get small depolarisation in long term light
Glutamate action
Product of postsynaptic receptor, not neurotransmitter
In visual system, glutamate is inhibitory!
Retinal map of rods and cones
At 0°, fovea
Cones concentrated here
Optic nerve is blind spot
Many rods in periphery, absent in centre of fovea
Receptive fields
Centre (direct to bipolar cell) of receptive field and surround (to horizontal cell) on retina
Directly underneath centre, horizontal and bipolar cell
Fields overlap
Bipolar cells
ON
- depolarise when no/less glutamate - light on, on
OFF
- depolarise where more glutamate - light off, on
Can have opposite reactions - focus to ON system.
ON system
Transmitter released from rods/cones is glutamate
Inhibition of bipolar cells, excitation of horizontal cells
Light -> less release glutamate, depolarise bipolar cells, hyperpolarise horizontal cells
On centre, off surround -> centre illumination
If shine light in centre, on response
If shine in surround, off response
Or can be off centre, on surround.
Ganglion cell receptive fields
Good for detecting changes in light levels
Some on, some off in static light
If suddenly lights on - more signalling from on centre, firing in ganglion cells (no change in surround)
If lights more - on centre and off surround (change across whole receptive field), and change in firing rate
-> good edge detection, to see where light changes, interpret outlines of objects
Lateral Geniculate Nucleus
Information - from rod/cone, left/right eye - remains separate in magnovellular (M) and parvovellular (P) pathways to LGN - no crossing of info other than nasal
Stay separate in LGN, recombine in visual cortex
Therefore, visual receptive fields of LGN identical to ganglion cells
Primary visual cortex
V1
Brodmann’s area 17
Most connections to layer 4 of cortex
Cells respond to bars of light of particular orientation - orientation selectivity
Most respond to info from both eyes - binocularly driven
Not colour sensitive (most)
Simple and complex cells
Simple cells in visual cortex
Respond best to specific orientation of stimulus bar in receptive field - not at all in some directions
Brain can then analyse best vs worst response, determine orientation of bar
Edge detection
Complex cells in visual cortex
Some respond to edge (light/dark border) crossing receptive field
- sensitive to orientation (like simple)
- insensitive to position (unlike simple)
Will show either on or off firing, no inbetween
Anatomical pathway of light detection
Rods and cones Bipolar cells in retina Ganglion cells in retina - optic nerve - Lateral geniculate nucleus - optic radiation - Primary visual cortex
Lesions in visual pathway
Right optic nerve - none right, all left
Optic chiasm - no lateral info
Right optic tract - no peripheral in left, no medial in right
If before LGN, lose in quarters
If in visual cortex, retain central (cutout), lose elsewhere
Because image inverted - peripheral to nasal
Substance abuse
Drug abuse – taking of drugs for non-medicinal reasons
Drug addiction – chronic, relapsing brain disease with compulsive drug seeking and use, despite harmful consequences. Psychological craving, physical withdrawal symptoms.
⇒ negative health consequences
- to feel good, feel better, perform better, peer pressure
Tolerance and dependence
Adaptive changes in response to the presence of the drug – acute -> desensitisation of receptor, chronic -> downregulation of receptor
Adaptive changes in pharmacokinetics – increased metabolism, enzyme induction
Drug addiction reward pathways
Dopamine
Serotonin (5-hydroxytryptamine)
Glutamate
Ventral tegmental area (VTA) to nucleus accumbens
Increased dopamine with positive outcomes
⇒ learning
Faster onset = better rush – smoking drug best for fast effects
Neurotransmitter/neuromodulatory systems
Dopamine Noradrenaline Serotonin (hallucinogens) Glutamate Acetylcholine (nicotine) Adenosine (caffeine) Endocannaboid (cannabis) Opioid (heroin)
Endogenous targets and their receptors – upregulate transmitter or block breakdown of drug, remain in system longer – to have effects
Meningitis definition
Inflammation of lepto-meningeal membranes (usually arachnoid and pia mater) Due to - infection - inflammation - parameningeal foci (eg close septic foci (sphenoid sinusitis)) - neoplastic or para-neoplastic Rare, very serious – 10% mortality ⇒ disability ⇒ deafness ⇒ paralysis ⇒ speech problems ⇒ epilepsy ⇒ neuro-psychiatric problems
Causative agents of meningitis
Mainly bacteria – S. pneumoniae, N. meningitidis
Virus
Fungus
Parasites
How does meningitis get into brain?
Blood brain barrier prevents infection reaching brain – no lymphoid tissue – immunological sanctuary mostly
BUT
- bacteraemia/viraemia/parasitaemia mainly, esp choroid plexus, or where vulnerable capillaries
- direct spread – chronic infections in cranial bones, ears, sinuses, oral cavity, upper resp tract
- neuronal spread – infected peripheral neurones, cell-cell spread eg rabies
Pathogenesis of meningitis (once in meninges)
Mucosal colonisation
Intravascular survival
Meningeal invasion
Survival in subarachnoid space
Inflammatory response, Increased BBB permeability, Cerebral vasculitis (as vessels clot and inflame)
Oedema, CSF flow disturbances
Increased ICP, Decreased cerebral blood flow
Loss of cerebro-vascular autoregulation -> coma, death
Predisposing factors for bacterial meningitis
- Extremes of age (newborns have underdeveloped BBB, elderly has degenerated)
- Geography – crowded housing
- Immunodeficiency
- Trauma/post-neurosurgery
Symptoms of meningitis
Fever
Neck stiffness
Headache
Altered mental status
Also more specific signs – if see is definitely meningitis, but only 5% will show these
- neck rigidity, Kernig’s sign, Brudzinski’s sign
(so diagnosis challenging – best test is lumbar puncture)
CSF findings in meningitis
Do lumbar puncture, to subarachnoid space
- measure pressure, cell count, protein, culture pathogens
- should be clear, sterile, low lymphocytes
Also many extra tests in CSF – PCR, virology, antigens etc
When to not do lumbar puncture
RAISED ICP - seizures - unconscious/low GCS - focal neurology - post trauma/neurosurgery - papilloedema Need imaging first. As if do LP with raised ICP, will get sudden drop in pressure, brain can herniate
Complications of bacterial meningitis
Seizures
Transtentorial herniation
Infarcts -> focal neurological deficits, hemiplesia, paraplesia etc
Hydrocephalus (enlarged ventricles)
Managing meningitis
SUPPORTIVE CARE
Specific antibiotic therapy – need to also consider CSF penetration (and route)
Steroids – unsure how helpful, but to bring down inflamed meninges
Surgical intervention - if complicated eg local antibiotics needed/hydrocephalus
(Prevent! Vaccines.)
CSF penetration antibiotics
GOOD
Penicillin, Ceftriaxone, Meropenem, Chloramphenicol
BAD
Vanomycin, Gentamicin
